CLINICAL DECISION

MAKING TOOLKIT

Instant guidance
2018 edition for diagnosis, risk management
and treatment
The
Clinical Decision Making
Toolkit is produced by the Acute Cardiovascular
Care Association (ACCA), developed and distributed
through an educational grant from AstraZeneca.
AstraZeneca was not involved in the development
of this publication and in no way influenced its content.
The Acute Cardiovascular Care Association
Clinical Decision-Making
TOOLKIT

Héctor Bueno, M.D., PhD., FESC

Editor in Chief
Pascal Vranckx, M.D., PhD
Associate Editor

ISBN: 978-2-9537898-7-4
 Preface
II
The best care of patients with acute cardiovascular syndromes
relies not only on specialists but also on systems of care that
involve many non-cardiologists. Several of these syndromes
require immediate diagnosis and decisions on treatment, The ACCA Toolkit is available
some of them life-saving. Critical decisions must often be through different platforms:
made quickly by professionals with different backgrounds
and levels of expertise with limited resources. This poses a • Printed booklet, available at congresses
significant clinical challenge. where ESC-ACCA is represented
Against this background, the ACCA Clinical Decision- • Web-based pdf file downloadable at:
Making Toolkit was created as a comprehensive resource www.escardio.org/ACCA
encompassing all aspects of acute cardiovascular care but
structured as an easy-to-use instrument in environments • Mobile application for smartphones/tablets
where initial acute cardiovascular care is typically initiated. available in both Apple & Googleplay stores
Comprehensive tables, clear diagrams and algorithms, based
on the ESC clinical practice guidelines as well as in clinical
experience should provide diagnostic and therapeutic
guidance at a glance.
Héctor Bueno
This 2018 Edition of the Clinical Decision Making Toolkit
has been updated with the 2016 and 2017 ESC Guidelines, M.D., PhD., FESC
a chapter on secondary prevention was added and the chapter Editor in Chief
on acute heart failure benefited a major update. However, it
does not replace textbooks and other sources of information
that need to be consulted to reach an optimal management
of these patients.
 7 DAYS F R O M C A R D I A C E V E N T
U NTI L PATI E NT S TA B I LISATI O N
C ARDIAC AR RE S T , S T E M I , A CS , A H F ,
C ARDIOGENIC S H O CK, A RRH YT H M I A S ,
VAS C ULAR S YN DRO M E S

E M E RG E N CY ROO M CCU G E NE R A L
C O R O NA R Y HO S P I TA L
PRE- HOS PITAL CA RE C A R E U NI T ICCU
I NTE NS I V E
CARDIAC
C A R E UNI T
 Contents
IV

List of Authors �������������������������������������������������������������������������������������������������������������������������� VI

CHAPTER 1: KEY SYMPTOMS

Chest Pain - M. Lettino, F. Schiele �������������������������������������������������������������������������������������������������� P. 2
Dyspnea - C. Müller ���������������������������������������������������������������������������������������������������������������������  P. 9
Syncope - R. Sutton �������������������������������������������������������������������������������������������������������������������  P. 16
CHAPTER 2: ACUTE CORONARY SYNDROMES
General concepts - H. Bueno ������������������������������������������������������������������������������������������������������ P. 24
Non ST-segment elevation ACS - H. Bueno ���������������������������������������������������������������������������������� P. 29
STEMI - P. Vranckx, B. Ibañez ������������������������������������������������������������������������������������������������������ P. 34
CHAPTER 3: SECONDARY PREVENTION AFTER ACS
General secondary prevention strategies and lipid lowering - H. Bueno, S. Halvorsen ����������������������� P. 38
Antithrombotic treatment - F. Costa, S. Halvorsen ������������������������������������������������������������������������  P. 41
CHAPTER 4: ACUTE HEART FAILURE
Wet-and-warm heart failure patient - V.P. Harjola, O. Miró ������������������������������������������������������������� P. 52
Cardiogenic shock (wet-and-cold) - P. Vranckx, U. Zeymer �������������������������������������������������������������  P. 61
 Contents (Cont.)
V

CHAPTER 5: CARDIAC ARREST AND CPR - N. Nikolaou, L. Bossaert ������������������������������������ P. 71

CHAPTER 6: RHYTHM DISTURBANCES
Supraventricular tachycardias and atrial fibrillation - J. Brugada ��������������������������������������������������  P. 80
Ventricular tachycardias - M. Santini, C. Lavalle, S. Lanzara ����������������������������������������������������������  P. 84
Bradyarrhythmias - B. Gorenek �������������������������������������������������������������������������������������������������� P. 87
CHAPTER 7: ACUTE VASCULAR SYNDROMES
Acute aortic syndromes - A. Evangelista �������������������������������������������������������������������������������������� P. 92
Acute pulmonary embolism - A. Torbicki ������������������������������������������������������������������������������������� P. 102
CHAPTER 8: ACUTE MYOCARDIAL/PERICARDIAL SYNDROMES
Acute myocarditis - A. Keren, A. Caforio �������������������������������������������������������������������������������������� P. 112
Acute pericarditis and cardiac tamponade - C. Vrints, S. Price ������������������������������������������������������� P. 117
CHAPTER 9: DRUGS IN ACUTE CARDIOVASCULAR CARE - A. de Lorenzo ���������������������� P. 121

Abbreviations ����������������������������������������������������������������������������������������������������������������������  P. 191

References and copyright acknowledgments �����������������������������������������������������������������  P. 199
 List of Authors
VI
Leo Bossaert Department of Medicine, University and University Hospital Antwerp, Antwerp,
Belgium
Josep Brugada Department of Cardiology, Hospital Clinic Universitat de Barcelona, Barcelona, Spain
Héctor Bueno Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC),
and Department of Cardiology, Hospital Universitario 12 de Octubre, Madrid, Spain
Alida Caforio Department of Cardiology, Padua University Medical School, Padua, Italy
Francesco Costa Cardiovascular institute, Hospital Clínic, University of Barcelona, Barcelona, Spain
Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
Artur Evangelista Department of Cardiology, Hospital Universitario Vall d’Hebrón, Barcelona, Spain
Bulent Gorenek Department of Cardiology, Eskisehir Osmangazy University, Eskisehir, Turkey
Sigrun Halvorsen Department of Cardiology, Oslo University Hospital Ulleval and University of Oslo, Oslo, Norway
Veli-Pekka Harjola Division of Emergency Medicine, Department of Emergency Care and Services, Helsinki
University Hospital, Finland
Borja Ibañez Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC),
and Department of Cardiology, University Hospital Fundación Jiménez Díaz, Madrid, Spain
Andre Keren Heart Failure and Heart Muscle Disease Centre, Hadassah University Hospital,
Jerusalem, Israel
 List of Authors (Cont.)
VII
Stefania Lanzara Department of Emergency, Ospedale Madre Giuseppina Vannini, Rome, Italy
Carlo Lavalle Department of Cardiology, Ospedale San Filippo Neri, Rome Italy
Maddalena Lettino Clinical Cardiology Unit, IRCCS Istituto Clinico Humanitas, Milano, Italy
Ana de Lorenzo Pharmacy Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain
Òscar Miró Emergency Department, Hospital Clínic, University of Barcelona, Barcelona, Catalonia, Spain
Christian Müller Department of Cardiology, University Hospital Basel, Basel,Switzerland
Nikolaos Nikolaou Departement of Cardiology, Konstantopouleio General Hospital, Athens, Greece
Susanna Price Consultant Cardiologist & Intensivist, Royal Brompton Hospital, London, United Kingdom
Massimo Santini Department of Cardiology, Ospedale San Filippo Neri, Rome, Italy
François Schiele Department of Cardiology, University Hospital Jean-Minjoz, Besancon, France
Richard Sutton Department of Cardiology, National Heart and Lung Institute Imperial College,
London, United Kingdom
Adam Torbicki Department of Pulmonary Circulation and Thromboembolic Diseases, Centre of
Postgraduate Medical Education, ECZ Otwock, Poland
Pascal Vranckx Department of Cardiology and Critical Care Medicine, Hartcentrum Hasselt, Hasselt, Belgium
Christiaan Vrints Department of Cardiology, Antwerp University Hospital, Edegem, Belgium
Uwe Zeymer Department of Cardiology, Herzzentrum Klinikum Ludwigshafen, Ludwigshafen, Germany
 1
P.1

CHAPTER 1
KEY SYMPTOMS

1.1 CHEST PAIN ����������������������������������������������������������������� p.2

M. Lettino, F. Schiele

1.2 DYSPNEA �������������������������������������������������������������������� p.9

C. Müller

1.3 SYNCOPE ������������������������������������������������������������������� p.16

R. Sutton
 Initial assessment of patients with CHEST PAIN 1.1
P.2
Low likelihood High likelihood
of Acute Coronary Syndrome of Acute Coronary Syndrome

1. Presentation

2. ECG

3. Troponin

Other
4. Diagnosis Noncardiac UA Cardiac NSTEMI STEMI

Reference: Roffi et al. Eur Heart J 2015; eurheartj.ehv320.

 Factors to be considered in the evaluation
after the first call for CHEST PAIN 1.1
P.3

First call for

chest pain Higher death risk / probability for ACS Lower death risk / probability for ACS

Arguments • Cardiorespiratory arrest, syncope/ • Normal consciousness

for vital risk loss of consciousness, neurological defect • Normal breathing
• Dyspnea (see chapter 1.2 page 9) • Normal heart rhythm
• Arrhythmias – tachycardia
Context, CV risk Age >40 years, previous CV disease • Age <40 years,
(MI, stroke, PE), modifiable CV risk factors • No previous CV disease
(smoker, HTN, hypercholesterolemia, diabetes), • No CV risk factors
chronic CV treatment • No chronic treatment
Chest Pain Medial/lateral thoracic pain, intense, • Depends on position/palpation/
with dyspnea movements
• Variable intensity, short duration (<1 min)
• Hyperthermia
Cardiac Retro-sternal, constriction, jaw/cervical/arm/back • Lateral, abdominal irradiation
Ischemic irradiation, spontaneous, prolonged >20 min + • No neuro-vegetative symptoms
Pain dyspnea, sweating, lightheadedness, nausea
 Approach after first call for out-of-hospital CHEST PAIN 1.1
P.4
APPROACH AFTER FIRST CALL FOR OUT-OF-HOSPITAL CHEST PAIN
VITAL RISK? (see chapter 1.1 page 3)

Emergency transport Yes No

with trained medical team

Likelihood of ACS
Emergency care:
Resuscitation, hemodynamic or
rhythm restoration (see chapter 5)

High probability for ACS Low probability for ACS

 1.1
P.5

Emergency transport Emergency transport

with trained medical team

Hospital admission
to the ED/CPU
ECG, decision for reperfusion,
antithrombotics, immediate
transport to ED/CPU/ICCU/Cathlab
(see chapter 2) Cardiology Non-cardiology Discharge after
ward ward prolonged observation
 Factors to be considered in the evaluation
during the first medical contact for CHEST PAIN 1.1
P.6

First medical contact Higher death risk / probability for ACS Lower death risk / probability for ACS

Hemodynamic, • Cardiopulmonary arrest, hypotension, tachycardia, • Normal consciousness, no motion defects

respiratory, neurological shock • Normal HR and BP
distress • Dyspnea, hypoxemia, lung rales (Killip class >2) • Normal breathing and SpO2,
• ECG: ST-segment deviation no loss of pulse
Probability for ACS • Context, typical symptoms consistent • No CV risk, atypical symptoms,
with myocardial ischemia normal ECG
• ECG changes • Negative hs cTn only if onset of pain
• Hs cTn >3 hours (see chapter 2.1 page 24)

STEMI NSTE-ACS Normal ECG (repeat 12-lead ECG

ECG criteria for STEMI
Uncertain diagnosis
(see chapter 2.1 page 24) ST depression or normal ECG
Type of reperfusion • Primary PCI or thrombolysis? Primary PCI if delay
<120 min (preferably <90 min)
or <60 min if onset of pain <120 min
Consider age, anterior wall location
Time assessment • Relevant times: Symptom onset, first medical
contact (FMC). FMC → ECG/diagnosis; FMC → PCI;
FMC → thrombolysis
recording if symptoms persist/recur)
Other ST-segment abnormalities
• Primary PCI between 12-48 hours
in patients with ongoing ischemia,
symptoms or clinical/haemodynamic
or electrical instability
• No reperfusion if delay >12 hours
and stable, asymptomatic, without
ST-segment elevation
 FIRST MEDICAL CONTACT IN PATIENTS WITH CHEST PAIN (HOME-AMBULANCE)
First medical contact in patients with CHEST PAIN (home-ambulance) 1.1

Hemodynamic, respiratory or neurological distress?

P.7

Yes No

Resuscitation, hemodynamic
or respiratory support ECG <10 min → ACS ?
(see chapters 4 & 5)

High probability Low probability

ST-segment elevation No ST-segment elevation but Suspect ACS

other ECG changes or persistent pain Uncertain diagnosis

Type of reperfusion (primary PCI or fibrinolysis)

Record times (symptom onset, FMC) No antithrombotic treatment
Transfer to a proximity centre
Start recommended medical therapy (with or without cath-lab)
(including antithrombotic drugs)
Transfer to a centre with cath-lab
Acute cardiovascular disease other than ACS?
Non cardiovascular disease?
• Acute aortic syndrome (see chapter 7)
• Sepsis
• Pulmonary embolism (see chapter 7)
• Acute respiratory distress
• Acute pericarditis (see chapter 8)
• GI disease, bleeding, others
• Acute heart failure (see chapter 4)
 MANAGEMENT OF PATIENTS WITH CHEST PAIN (EMERGENCY ROOM)
Management of patients with CHEST PAIN (emergency room) 1.1

Hemodynamic, respiratory or neurological distress?

P.8

Other CVD
Yes No
or No ACS

STEMI,
Resuscitation, hemodynamic NSTE-ACS with persistent pain,
or respiratory support Hemodynamic distress
(see chapters 4 & 5)
Yes No

Direct transfer to cath-lab No direct transfer to cath-lab

→ ED, Chest Pain Unit,
cardiology ward, other wards
STEMI (see chapter 2) Complicated NSTEMI

• Diagnosis of NSTE-ACS (see chapter 2)

• Acute aortic syndrome (see chapter 7)
• Acute pulmonary embolism (see chapter 7) Repeat clinical and ECG examination
• Acute pericarditis (see chapter 8) Laboratory: cTn, renal function, Hb,
• Acute heart failure (see chapter 4) D-dimers
• Aortic stenosis, hyperthrophic cardiomyopathy Imaging: TTE, CT scan
• Acute gastro-oesophageal disease Diagnostic coronary angiography
• Acute pleuro-pulmonary disease
• Acute psychogenic disorders
 DYSPNEA: Diferential diagnosis 1.2
DYSPNEA: DIFERENTIAL DIAGNOSIS
P.9
50% have ≥ 2 diagnoses, which may result in acute respiratory failure*!

Basic measures Criteria for transfer to ICU

(despite treatment for 30 minutes)
• BP, HR, respiratory rate, SpO2 & temperature
• Start oxygen to target SpO2 94-98% • Respiratory rate >35/min • SBP <90 mmHg
• Start i.v. line & monitor patient • SpO2 <85% • HR >120 bpm

Investigations: • ECG • Chest X-ray • Blood count • cTn

• BNP • Venous BG • D-dimers if suspicion of PE

Acute heart Exacerbated COPD Pulmonary Other causes, including

failure Pneumonia • Asthma
or other chronic embolism
lung disease • Severe sepsis
Acute coronary • Tumor
syndrome • Pneumothorax
• Pleural effusion/ascites
* Defined as ≥1 criterion: • Anxiety disorder
• Respiratory rate ≥25/min • Anemia
• PaO2 ≤75 mmHg • Bronchitis
• SpO2 ≤92% in ambient air • Metabolic acidosis
• PaCO2 ≥45 mmHg with arterial pH ≤7.35 • Neurologic disease

Reference: Ray P et al. Acute respiratory failure in the elderly: etiology, emergency diagnosis and prognosis. Critical Care (2006); 10 (3):R82.
 DYSPNEA: Acute heart failure (see chapter 4.1) 1.2
BASIC WORK-UP P.10
• Immediate 12-lead ECG, cardiac monitor, BP, respiratory rate, • Chest X-ray (lung ultrasound)
pulse oximetry • Echocardiogram
• Clinical findings During admission (earlier if decompensated
Most commonly: lower extremity edema, jugular venous aortic stenosis or endocarditis are suspected)
distension, rales, work up for underlying cardiac disease and triggers • Coronary angiography
• Laboratory findings Emergent in patients with ACS; delayed in
Complete blood count, chemistries, cardiac enzymes, BNP, patients with suspected coronary artery disease
TSH, ABG as needed

• Positioning Keep head of bed elevated above level of legs

• Oxygen Up to 12 l/min via rebreather mask, titrate oxygen saturation to 94%
• Nitroglycerin 1-2 SL tablets or 2-3 patches 10 mg (1st choice). In pulmonary edema with severe shortness
of breath: NTG drip 0.05% (100 mg in 200 ml)
- Start with 25 µg/min = 3 ml/h, check BP after 5 and 10 min
- Increase dose by 25 µg/min at a time as long as SBP >90 mmHg
- Additional BP check 5 and 10 min after each increase in dosing
- Check BP every 20 min once a steady drip rate is reached
• Furosemide 40-120 mg i.v. (adjust based on kidney function and clinical findings; monitor creatinine)
• Morphine 2 mg i.v. (preceeded by 10 mg i.v. metoclopramide PRN) if patient is in severe dyspnoea
• Consider digoxin 0.5 (-1.0) mg i.v. in patients with atrial fibrillation
• Anticoagulation Therapeutic dosing in ACS and atrial fibrillation: Enoxaparin 1 mg/kg body weight as 1st dose
 1.2
P.11

Unstable after 30 minutes Stable after 30 minutes

CCU/ICU transfer Ward transfer

Reference: Ware L B and Matthay M A. Acute Pulmonary Edema. New Engl J Med (2005); 353:2788-2796.
 DYSPNEA: Acute pulmonary embolism (see chapter 7.2) 1.2
P.12
Priorities: 1. Vital signs 2. Diagnostic screening dependent upon clinical stratification

ABG, ECG, chest X-ray plus clinical assessment of PE probability (risk factors) plus monitoring

Hemodynamically unstable Hemodynamically stable

Initiate transfer to ICU Wells criteria for PE:

Score
• Clinical signs and symptoms of
deep vein thrombosis (DVT) + 3.0
• No alternative diagnosis (or alternative
Immediate TTE (if available)
diagnosis less likely than PE) + 3.0
• Heart rate >100/min + 1.5
• Immobilization or operation within
the last 4 weeks + 1.5
• Previous DVT or PE + 1.5
Result Right
• Hemoptysis + 1.0
inconclusive ventricular
• Malignant tumor with treatment within the
→ CT-angio dysfunction
last 6 months or palliative care + 1.0
 1.2
P.13
PE confirmed: Treatment
(see chapter 7.2)

Outpatient management possible? Low Intermediate High

→ Risk stratification probability probability probability
(see chapter 7.2) Total score <2 Total score 2-6 Total score >6

Copyright: Stein PD, Woodard PK, Weg JG, et al. Diagnostic pathways in acute pulmonary embolism: recommendations of the PIOPED II investigators.
Am J Med (2006); 119:1048–55. - Goldhaber SZ. Pulmonary embolism. Lancet (2004); 363 (9417) 1295-1305. - Agnelli G and Becattini C. Acute Pulmonary
Embolism. New Engl J Med (2010); 363:266-274.
 DYSPNEA: COPD exacerbation 1.2
DYSPNEA: COPD EXACERBATION P.14
• Verify diagnosis (DD: PE, acute heart failure, pneumothorax)
• Oxygen administration → SpO2 target 88-92% (Beware of carbonarcosis: ABC after 1 h)

Definition: • COPD classification

Known COPD and/or • Progressive dyspnea and/or (GOLD)
• Change in quantitiy and color of sputum and/or
• Heavy coughing • Etiology

• History, clinical examination (blood pressure, pulse, oxygen saturation, vigilance)

• Laboratory findings: Blood count, coagulation, ProCT, perhaps BNP, D-Dimers • Hospitalisation indicated?
• Chest X-ray; ECG (exclusion of differential diagnoses)
• Sputum cultures (always in case of hospitalisation or previous • Evaluate ICU criteria
outpatient antibiotic treatment) • NIV indicated?

• Oxygen therapy 2-(4) l; target saturation 90%

• Salbutamol/ipratropium inhalations ≥4-6 x/d, if needed long-term inhalation
• Systemic steroids prednisone 0.5 mg/kg of body weight for 5 days • Follow-up
• Antibiotic treatment should be considered; always indicated in stage Gold IV
• Physiotherapy

Copyright: Leuppi JD et al. JAMA. 2013 Jun 5; 309(21):2223-31.

 DYSPNEA: Community-acquired pneumonia 1.2
DYSPNEA: COMMUNITY-ACQUIRED PNEUMONIA
P.15
Objective: diagnostics, risk stratification & empirical immediate treatment <2(-4) hours

Definition

• Chest X-ray if dyspnea & cough

• Laboratory workup clinical chemistry; BGA; procalcitonin
• Sputum if patient admitted
• Blood cultures (2x2) if patient admitted
• Legionella antigen (urine) if Legionellosis suspected
• Pneumococcus antigen (urine) if no other pathogen isolated

Risk stratification → manageable on an outpatient basis?

- Pneumonia Severity Index
- CURB-65

• Treatment; procalcitonin guided treatment

• Consider outpatient treatment where PSI I-III or CURB65 0 or 1
• Minimum 5-day course of treatment and afebrile for 48-72h, 7-10 days,
14 days where intracellular organisms (e.g. Legionella) are present

Complications

Copyrights: Mandell LA et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired
pneumonia in adults. Clin Infect Dis. (2007); 44 Suppl 2:S27-72. - Halm EA and Teirstein AS. Management of Community-Acquired Pneumonia New Engl J Med
(2002); 347:2039-2045. - Woodhead M et al. Guidelines for the management of adult lower respiratory tract infections ERJ December 1, (2005); 26 (6) 1138-1180.
 SYNCOPE: Assessment of patients
with transient loss of conscioussness (TLOC) 1.3
P.16
Syncope is a transient loss of consciousness due to global cerebral hypoperfusion (usually, itself due to
period of low blood pressure) characterised by rapid onset, short duration, spontaneous and complete recovery.

The differentiation between syncope and non-syncopal conditions with real or apparent LOC can be achieved
in most cases with a detailed clinical history but sometimes can be extremely difficult. The following
questions should be answered:
• Was LOC complete?
• Was LOC transient with rapid onset and short duration?
• Did the patient recover spontaneously, completely and without sequelae?
• Did the patient lose postural tone?

If the answers to these questions are positive, the episode has a high likelihood of being syncope. If the answer to
one or more of these questions is negative, exclude other forms of LOC before proceeding with syncope evaluation.
No • Accidental • Fall
Loss of Consciousness?
• Other abnormal mental state
Yes
Transient, rapid onset, No • Coma • Metabolic disturbance
short time, self-terminating • Intoxication • Aborted sudden death
Yes

Trauma TLOC Not Trauma

Syncope Epilepsy Psychogenic

Reference: Sutton R. Clinical classification of syncope. - Prog Cardiovasc Dis. (2013); 55(4):339-44.
 SYNCOPE: Diagnostic criteria (1)
Diagnostic criteria with initial evaluation 1.3
P.17

Vasovagal syncope is diagnosed if syncope is precipitated by emotional distress or orthostatic stress

and is associated with typical prodrome.
Situational syncope is diagnosed if syncope occurs during or immediately after specific triggers.
Orthostatic syncope is diagnosed when it occurs after standing up and there is documentation
of orthostatic hypotension.
Arrhythmia related syncope is diagnosed by ECG when there is:
• Persistent sinus bradycardia <40 bpm in awake or repetitive sinoatrial block or sinus pauses >3 s
• Mobitz II 2nd or 3rd degree AV block
• Alternating left and right BBB
• VT or rapid paroxysmal SVT
• Non-sustained episodes of polymorphic VT and long or short QT interval
• Pacemaker or ICD malfunction with cardiac pauses
Cardiac ischemia related syncope is diagnosed when syncope presents with ECG evidence of acute ischemia
with or without myocardial infarction.
Cardiovascular syncope is diagnosed when syncope presents in patients with prolapsing atrial myxoma, severe
aortic stenosis, pulmonary hypertension, pulmonary embolus or acute aortic dissection.

Reference: Moya A et al. Eur Heart J(2009) 30, 2631–2671 (1).

 SYNCOPE: Evaluation and risk stratification of patients
with suspected syncope 1.3
Once syncope is considered to be the likely diagnosis, risk stratification is required to determine further management. P.18

Patients with suspected syncope presenting to ED or clinic

“Uncertain” or unexplained syncope Certain diagnosis of syncope

Initiate therapy
Inpatient SMU, outpatient SMU or
Risk stratification personal physician as appropriate

High risk Intermediate risk Low risk

Observation Unit Home

Home if stable, Outpatient SMU
Admit to hospital referral
if evidence of high risk

Hospital admission Outpatient SMU for diagnosis, treatment

Inpatient SMU and follow-up as appropriate

Copyright: Sutton R, Brignole M, Benditt DG. Key challenges in the current management of syncope. Nat Rev Cardiol. (2012 ); (10):590-8.
 SYNCOPE: Diagnostic criteria (2)
Diagnostic criteria with provocation maneuvers
Carotid sinus massage
Indications
• CSM is indicated in patients >40 years with syncope
of unknown aetiology after initial evaluation;
• CSM should be avoided in patients with previous MI,
TIA or stroke within the past 3 months and in
patients with carotid bruits (except if carotid Doppler
studies excluded significant stenosis)
Diagnostic criteria
• CSM is diagnostic if syncope is reproduced in presence
of asystole longer than 3 s and/or a fall in systolic
BP >50 mmHg
Reference: Moya A et al. Eur Heart J(2009) 30; 2631–2671 (2).
1.3
P.19
Orthostatic Hypotension
Recommendations: Active standing Indications
• Manual intermittent determination with
sphygmomanometer of BP supine and, when OH
is suspected, during active standing for 3 min is
indicated as initial evaluation;
• Continuous beat-to-beat non-invasive pressure
measurement may be helpful in cases of doubt
Diagnostic criteria
• The test is diagnostic when there is a symptomatic
fall in systolic BP from baseline value ≥20 mmHg
or diastolic BP ≥10 mmHg or a decrease in systolic BP
to <90 mmHg;
• The test should be considered diagnostic when there
is an asymptomatic fall in systolic BP from baseline
value ≥20 mmHg or diastolic BP >10 mmHg
or a decrease in systolic BP to <90 mmHg
 Treatment according to type of SYNCOPE (1) 1.3
P.20

Treatment of reflex syncope Treatment of orthostatic hypotension

• Explanation of the diagnosis, provision of reassurance and explanation • Adequate hydration and salt
of risk of recurrence are in all patients intake must be maintained
• Isometric PCM are indicated in patients with prodrome • Midodrine should be administered
• Cardiac pacing should be considered in patients with dominant as adjunctive therapy if needed
cardioinhibitory CSS • Fludrocortisone should be
• Cardiac pacing should be considered in patients with frequent recurrent reflex administered as adjunctive
syncope, age >40 years and documented spontaneous cardioinhibitory response therapy if needed
during monitoring • PCM may be indicated
• Midodrine may be indicated in patients with VVS refractory to lifestyle measures • Abdominal binders and/or support
• Tilt training may be useful for education of patients but long-term benefit depends stockings to reduce venous
on compliance pooling may be indicated
• Cardiac pacing may be indicated in patients with tilt-induced cardioinhibitory • Head-up tilt sleeping (>10°)
response with recurrent frequent unpredictable syncope and age >40 after to increase fluid volume
alternative therapy has failed may be indicated
• Triggers or situations inducing syncope must be avoided as much as possible • Triggers or situations inducing
• Hypotensive drugs must be modified or discontinued syncope must be avoided
as much as possible
• Cardiac pacing is not indicated in the absence of a documented cardioinhibitory
reflex • Hypotensive drugs administered
for concomitant conditions must
• Beta-adrenergic blocking drugs are not indicated
be discontinued or reduced
• Fluid consumption and salt in the diet should be increased

Copyright: Moya A et al. Eur Heart J(2009) 30; 2631–2671 (3).

 Treatment according to type of SYNCOPE (2)
Treatment of arrhythmic syncope
Cardiac Pacing
• Pacing is indicated in patients with sinus node disease in
whom syncope is demonstrated to be due to sinus arrest
(symptom-ECG correlation) without a correctable cause
• Pacing is indicated in sinus node disease patients with
syncope and abnormal CSNRT
• Pacing is indicated in sinus node disease patients with
syncope and asymptomatic pauses >3 sec. (with possible
exceptions of young trained persons, during sleep and in
medicated patients)
• Pacing is indicated in patients with syncope and 2nd degree
Mobitz II, advanced or complete AV block
• Pacing is indicated in patients with syncope,
BBB and positive EPS
• Pacing should be considered in patients with unexplained
syncope and BBB
• Pacing may be indicated in patients with unexplained
syncope and sinus node disease with persistent sinus
bradycardia itself asymptomatic
• Pacing is not indicated in patients with unexplained syncope
without evidence of any conduction disturbance
Copyright: Moya A et al. Eur Heart J(2009) 30; 2631–2671 (4).
1.3
P.21
Catheter ablation
• Catheter ablation is indicated in patients with symptom/
arrhythmia ECG correlation in both SVT and VT in the
absence of structural heart disease
(with exception of atrial fibrillation)
• Catheter ablation may be indicated in patients with syncope
due to the onset of rapid atrial fibrillation
Antiarrhythmic drug therapy
• Antiarrhythmic drug therapy, including rate control drugs,
is indicated in patients with syncope due to onset of rapid
atrial fibrillation
• Drug therapy should be considered in patients with
symptom/ arrhythmia ECG correlation in both SVT and VT
when catheter ablation cannot be undertaken or has failed
Implantable Cardioverter Defibrillator (ICD)
• ICD is indicated in patients with documented VT
and structural heart disease
• ICD is indicated when sustained monomorphic VT is induced
at EPS in patients with previous myocardial infarction
• ICD should be considered in patients with documented VT
and inherited cardiomyopathies or channelopathies
 2

CHAPTER 2
ACUTE CORONARY SYNDROMES

2.1 GENERAL CONCEPTS ������������������������������������������������������ p.24

H. Bueno

2.2 NON ST-SEGMENT ELEVATION ACS ��������������������������������������� p.29

H. Bueno

2.3 ST-SEGMENT ELEVATION MI (STEMI) �������������������������������������� p.35

P. Vranckx, B. Ibañez
 ACUTE CORONARY SYNDROMES: Diagnosis (1)
ACUTE CORONARY SYNDROMES: DIAGNOSIS 2.1
CHEST PAIN P.24
or symptoms sugestive of myocardial ischemia

ECG

ST elevation Repolarization not interpretable ST/T abnormalities Normal ECG

(persistent) (i.e. LBBB, pacemaker...)

Pain resolves with Yes

nitroglycerin 1st hsTn

No hs-cTn>ULN hs-cTn<ULN
Potential
Consider noncardiac
STEMI causes for Pain onset <6 h Pain onset >6 h
abnormal Tn
hs-cTn >x5 ULN Re-test hs-cTn (3h later)
or See next page for 1 h rule-in & rule-out algorithm
clinical
diagnosis
clear ∆ hs-cTn hs-cTn
(1 value >ULN) no change
STEMI

References: Roffi M. Eur Heart J 2016; 37:267-315.

Work-up
NSTEMI Unstable Angina differential diagnoses
Ibañez B. Eur Heart J 2018; 39:119-177.
 ACUTE CORONARY SYNDROMES: Diagnosis (2)
0-1 H Rule-in & rule out test for NSTEMI 2.1
P.25
Suspected NSTEMI

0h<B ng/l 0h≥D ng/l

0h<A ng/l or and Other or
0-1h<Cng/l 0-1h≥ E ng/l

Rule-out Observe Rule-in

A B C D E
hs-cTnT (Elecsys)* 5 12 3 52 5
hs-cTnl (Architect)* 2 5 2 52 6
hs-cTnl (Dimension Vista)* 0,5 5 2 107 19
*Cut-off levels are assay-specific.

• NSTEMI can be ruled-out at presentation, if hs-cTn concentration is very low

• NSTEMI can be ruled out by the combination of low baseline levels and the lack of a relevant increase within 1 h
• NSTEMI is highly likely if initial hs-cTn concentration is at least moderately elevated or hs-cTn concentrations
show a clear rise within the first hour
Reference: Roffi M. Eur Heart J 2016; 37:267-315.
 ACUTE CORONARY SYNDROMES: Differential diagnosis (1)
Causes of chest pain
Not related to ACS
Primary cardiovascular
• Acute pericarditis, pericardial effusion
• Acute myocarditis
• Severe hypertensive crisis
• Stress cardiomyopathy (Tako-Tsubo syndrome)
• Hypertrophic cardiomyopathy, aortic stenosis
• Severe acute heart failure
• Acute aortic syndrome (dissection, hematoma)
• Pulmonary embolism, pulmonary infarction
• Cardiac contusion
Primary non-cardiovascular
• Oesophageal spasm, oesophagitis, Gastro
Esophageal Reflux (GER)
• Peptic ulcer disease, cholecystitis, pancreatitis
• Pneumonia, bronchitis, asthma attack
• Pleuritis, pleural effusion, pneumothorax
• Pulmonary embolism, severe pulmonary
hypertension
• Thoracic trauma
• Costochondritis, rib fracture
• Cervical / thoracic vertebral or discal damage
• Herpes Zoster
2.1
P.26
Causes of troponin elevation
Not related to ACS
Primary cardiovascular
• Acute myo(peri)carditis
• Severe hypertensive crisis
• Pulmonary edema or severe congestive heart failure
• Stress cardiomyopathy (Tako-Tsubo syndrome)
• Post- tachy- or bradyarrhythmias
• Cardiac contusion or cardiac procedures
(ablation, cardioversion, or endomyocardial biopsy)
• Aortic dissection, aortic valve disease or hypertrophic cardiomyopathy
• Pulmonary embolism, severe pulmonary hypertension
Primary non-cardiovascular
• Renal dysfunction (acute or chronic)
• Critical illness (sepsis, repiratory failure…)
• Acute neurological damage (i.e. stroke, subarachnoid hemorrhage)
• Severe burns (affecting >30% of body surface area)
• Rhabdomyolysis
• Drug toxicity (chemotherapy with adriamycin, 5-fluorouracil,
herceptin, snake venoms…)
• Inflammatory or degenerative muscle diseases
• Hypothyroidism
• Infiltrative diseases (amyloidosis, hemochromatosis, sarcoidosis)
• Scleroderma
 ACUTE CORONARY SYNDROMES: Differential diagnosis (2)
Causes of repolarisation abnormalities in the ECG not related to ACS 2.1
P.27
ST-segment elevation Negative T waves

Fixed • Normal variants, i.e. women

• LV aneurysm (right precordial leads),
• LBBB, WPW, hypertrophic cardiomyopathy, LVH children, teenagers
• Pacemaker stimulation • Evolutive changes post
• Early repolarisation (elevated J-point) myocardial infarction
Dynamic • Chronic ischemic heart disease
• Acute (myo)pericarditis • Acute (myo)pericarditis,
• Pulmonary embolism cardiomyopathies
• Electrolyte disturbances (hyperkalemia) • BBB, LVH, WPW
• Acute brain damage (stroke, subarachnoid haemorrhage) • Post-tachycardia or
• Tako Tsubo syndrome pacemaker stimulation
• Metabolic or ionic disturbances

ST-segment depression Prominent T waves

Fixed
• Abnormal QRS (LBBB, WPW, pacemaker stimulation…)
• LVH, hypertrophic cardiomyopathy
• Chronic ischemic heart disease
Dynamic
• Acute (myo)pericarditis
• Acute pulmonary hypertension
• Electrolyte disturbances (hyperkalemia)
• Intermitent LBBB, WPW, pacing
• Post-tachycardia / cardioversion
• Normal variants, i.e.
early repolarisation
• Metabolic or ionic disturbances
(i.e. hyperkalemia)
• Acute neurological damage
•S evere hypertensive crisis (stroke, subarachnoid haemorrhage)
• Drug effects (digoxin)
• Shock, pancreatitis
• Hyperventilation
• Tako Tsubo syndrome
 GENERAL APPROACH
to the patient with chest pain/suspected ACS 2.1
GENERAL APPROACH TO THE PATIENT WITH CHEST PAIN / SUSPECTED ACS
P.28
1 2 3 4 5
Clinical ECG Diagnosis / Medical Invasive
Evaluation (<10 min) Risk assessment Treatment Strategy

STEMI (see chapter 2.3) Primary

PCI
Thrombolysis
for STEMI if
primary PCI not
• Clinical presentation timely available Emergent
(BP, HR) <2 hours
Quality of • ECG presentation
chest pain • Past history Anti-ischemic Urgent
Clinical • Ischemic risk therapy 2-24 hours
context (i.e. GRACE, TIMI scores)
ECG NSTE ACS Antiplatelet
Probability (see chapter 2.2) • Bleeding risk therapy
of CAD Early
(i.e. CRUSADE score) Anticoagulation 24-72 hours
Physical
examination • Additional information
(labs, imaging...) optional
No /
ACS unclear Elective
(Rule out ACS) Chest Pain Unit (see chapter 1.1)

No ACS Rule out noncardiac causes

 NON ST-SEGMENT ELEVATION ACS: Risk stratification (1) 2.2
P.29
Ischemic risk
GRACE risk score TIMI risk score
Predictive Factors Predictive Factors
• Age • Age 65 years
• HR* • At least 3 risk factors for CAD
• SBP* • Significant (>50%) coronary stenosis
• Creatinine (mg/dl)* Probability of all-cause mortality from
• Killip class*
hopital discharge to 6 months (%) • ST deviation
• Cardiac arrest*
50 • Severe anginal symptoms (>2 events in last 24h)
• ST-segment deviation 40 • Use of aspirin in last 7 days
• Elevated cardiac markers • Elevated serum cardiac markers
30

Outcomes 20 Outcome 50 Risk of 14 days events (%)

In-hospital, 6-month, 10
All-cause mortality/new 40
1-year and 3-year mortality or recurrent MI/severe 30
1-year death/MI 0
recurrent ischemia requiring 20
70 90 110 130 150 170 190 210

GRACE Risk Score urgent revascularisation at 10

14 days 0
0-1 2 3 4 5 >=6
TIMI Risk Score
Risk calculation Risk calculation
http://www.gracescore.org/WebSite/WebVersion.aspx http://www.timi.org/index.php?page=calculators

* At admission.
 NON ST-SEGMENT ELEVATION ACS: Risk stratification (2) 2.2
P.30
Bleeding risk
CRUSADE risk score
Predictive Factors Risk calculation
• Sex www.crusadebleedingscore.org
• HR*
• SBP* Probability of in-hospital major bleeding(%)
• Creatinine (mg/dl)* 50

• Baseline hematocrit* 40
• GFR: Cockcroft-Gault*
30
• Diabetes
• Prior vascular disease 20

• Signs of congestive heart failure* 10

Outcome 0
0 20 40 60 80 100
In-hospital major bleeding
CRUSADE Bleeding Score

* At admission.

Copyrights: Eagle KA et al. A validated prediction model for all forms of acute coronary syndrome: estimating the risk of 6-month post-discharge death
in an international registry. JAMA. (2004); 291(22):2727-33. - Antman EM, et al. The TIMI risk score for unstable angina/non-ST elevation MI: A method
for prognostication and therapeutic decision making. JAMA. (2000); 284(7):835-42. - Subherwal S, et al Baseline risk of major bleeding in non-ST-segment-
elevation myocardial infarction: the CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation
of the ACC/AHA Guidelines) Bleeding Score. Circulation (2009); 119(14):1873-82.
 NON ST-SEGMENT ELEVATION ACS: Treatment (1)
General overview 2.2
P.31
Initial treatment*
• Nitrates Pharmacological Myocardial
• Morphine treatment* revascularisation
• Oxygen (if SpO2 <90%)

Antithrombotic Anti ischemic Other preventive

therapy treatment therapies
PCI
• Nitrates • Statins CABG
• Beta-blockers • ACE inh. (or ARB)
• Calcium antagonists • Aldosterone inhibitors

Anticoagulation Antiplatelets
One of the following: Aspirin + one of: Optionally:
• Fondaparinux • Ticagrelor • GP IIb/IIIa inhibitors
• Enoxaparin • Prasugrel • Cangrelor
• UFH • Clopidogrel
• Bivalirudin

*
For more information on individual drug doses and indications,
SEE CHAPTER 3 SECONDARY PREVENTION AFTER ACS & CHAPTER 9 DRUGS USED IN ACUTE CARDIOVASCULAR CARE
 NON ST-SEGMENT ELEVATION ACS: Treatment (2)
Risk criteria mandating invasive strategy in NSTE-ACS 2.2
P.32

Very-high-risk • Haemodynamic instability or cardiogenic shock

criteria • Recurrent or ongoing chest pain refractory to medical treatment
• Life-threatening arrhythmias or cardiac arrest
• Mechanical complications of MI
• Acute heart failure
• Recurrent dynamic ST-T wave changes, particularly with intermittent ST-elevation

High-risk criteria • Rise or fall in cardiac troponin compatible with MI

• Dynamic ST- or T-wave changes (symptomatic or silent)
• GRACE score >140
Intermediate-risk • Diabetes mellitus
criteria • Renal insufficienty (eGFR <60 ml/min/1.73 m2)
• LVEF <40% or congestive heart failure
• Early post-infarction angina
• Prior PCI
• Prior CABG
• GRACE risk score >109 and <140

Low-risk criteria • Any characteristics not mentioned above

Reference: Roffi M. Eur Heart J 2016; 37:267-315.

 NON ST-SEGMENT ELEVATION ACS: Treatment (3)
Timing and strategy for invasive management 2.2
P.33
Symptoms Onset

First medical contact NSTE-ACS diagnosis

PCI centre EMS or Non–PCI centre

Immediate transfer to PCI centre

Very high Very high
Risk stratification

Same-day transfer
High High

Transfer
Intermediate Intermediate

Transfer optional
Low Low
Therapeutic
strategy

Immediate Early invasive Invasive Non-invasive

Invasive (<2 hr) (<24 hr) (<72 hr) testing if appropriate

Reference: Roffi M. Eur Heart J 2016; 37:267-315.

 STEMI Treatment (1):
Reperfusion strategy 2.3
Time to PCI? P.34

ECG STEMI diagnosis ≤120min >120min

0

Alert & transfer Primary PCI Fibrinolysis

to PCI centre strategy strategya

Bolus of
10 min
fibrinolyticb
Strategy clock

Transfer

60-90min
to PCI centre
Wire crossing
90 min

≥120min
(reperfusion)

Rescue No Meet reperfusion Yes

PCI criteria?

2 hours
Routine PCI strategy
24 hours
a
If fibrinolysis is contra-indicated, direct for primary PCI strategy regardless of time to PCI.
b
10 min is the maximum target delay time from STEMI diagnosis to fibrinolytic bolus administration, however, it should be given as soon as
possible after STEMI diagnosis (after ruling out contra-indications).
Reference: Ibañez B. Eur Heart J 2018; 39:119-177.
 STEMI Treatment (2): 2.3
Medical management of patients treated with primary PCI
P.35
Oxygen when SpO2 <90%
STEMI Aspirin Prasugrel or ticagrelor loading
i.v. Beta-blocker
diagnosis Loading (clopidogrel as alternative)
i.v. Opioids/tranquilizer

Wire crossing DURING PCI: radial access, UFH (enoxaparin/bivalirudin as alternatives)

(reperfusion)

High dose statin

(e.g. atorvastatin 80 mg or rosuvastatin 40 mg)
Hospital
Admission
Oral β-blocker

ACE inhibitor

Hospital Mineralocorticoid receptor antagonist

Discharge (if LVEF <40% and heart failure)
Aspirin Prasugrel or ticagrelor maintenance
maintenance (clopidogrel as alternative)

Reference: Ibañez B. Eur Heart J 2018; 39:119-177.

 STEMI Treatment (3): 2.3
Medical management of patients treated with fibrinolysis
P.36
Oxygen when SpO2 <90%
STEMI Fibrinolysis bolus Enoxaparin
diagnosis i.v. Opioids/tranquilizer

Aspirin Clopidogrel
10min
loading loading

High dose statin

(e.g. atorvastatin 80 mg or rosuvastatin 40 mg)
Hospital Coronary angiography ± PCI
Admission (2-24h)
Oral β-blocker

ACE inhibitor

Hospital Mineralocorticoid receptor antagonist

Discharge (if LVEF <40% and heart failure)
Aspirin Clopidogrel
maintenance maintenance

Reference: Ibañez B. Eur Heart J 2018; 39:119-177.

 3
P.37
CHAPTER 3
SECONDARY PREVENTION
AFTER ACS
3.1 GENERAL SECONDARY PREVENTION STRATEGIES
AND LIPID LOWERING ����������������������������������������������������� p.38
H. Bueno, S. Halvorsen

3.2 ANTITHROMBOTIC TREATMENT ������������������������������������������� p.41

F. Costa, S. Halvorsen
 SECONDARY PREVENTION STRATEGIES after ACS 3.1
P.38

Hospitalization Acute Coronary Syndrome

1- Acute care
• Drug therapy
• Coronary revascularisation
2- Cardiovascular risk assessment (e.g. concealed and uncontrolled risk factors)
3- Initiate secondary prevention and set treatment goals

Plan and schedule Education Cardioprotective drugs

Cardiac Rehabilitation and counselling in secondary prevention

• Risk factor control (e.g. Antithrombotic Lipid BP/LVD/ Glucose

weight control, smoking cessation,
therapy lowering HF control control
blood pressure and lipid control)
• Diet/nutritional counseling Aspirin + P2Y12 High intensity ACEI / ARB*, Metformin
• Physical activity counseling/ inhibitor statin therapy Beta-blockers*, Insulin*
excercise training
(12 months) MRA*
Cardiac • Psychosocial management,
Rehabilitation sex advice
programme • Vocational advice
 3.1
P.39

Re-evaluate lifestyle, control of risk factors, psychosocial factors and adherance to therapy
Adjustment of secondary prevention therapies. Consider polypill, if needed

Reinforce education
Psychosocial support After 12 months Consider adding Consider Consider
consider*: Ezetimibe* dose adjustment SGLT2 inhibitor*
After Discharge Ticagrelor PCSK9 inhibitor* Consider ARNI* GLP-1 agonists*
60 mg bid

Anticoagulation?**

* When individually indicated and without specific contraindications. - ** Rivaroxaban 2.5 mg bid pending approval for indication in chronic CAD.

Reference modified from Cortés-Beringola A. Eur J Prev Cardiol 2017; 24(3 suppl): 22-28.
 After ACS: POTENTIAL STRATEGIES
TO OPTIMIZE SECONDARY PREVENTION THERAPY 3.1
P.40

Potential strategies to optimize secondary prevention therapy after ACS

• Participation in a comprehensive, multi-disciplinary cardiac
rehabilitation programme after hospital discharge

• Coordination with primary care provider

(and other specilaists) in therapeutic plan and objectives

• Re-check and reinforce advise on all lifestyle changes

(diet, physical activity, smoking cessation…) during follow-up visits

• Check and optimise doses of all indicated secondary prevention drugs

• Use of specialist support, nicotine replacement therapies, varenicline,

and/or bupropion individually or in combination
for patients who do not quit or restart smoking

• Use of ezetimibe and/or a PCSK9 inhibitor in patients

who remain at high risk with LDL-cholesterol >70 mg/dl despite
apropriate diet and maximally tolerated doses of statins

• Use of a polypill or combination therapy in patients

with suboptimal adherence to drug therapy
 ANTITHROMBOTIC TREATMENT:
Dual antiplatelet therapy duration in patients with ACS (1) 3.2
P.41
PCI

Treatment Stable CAD ACS

indication

Device used DES/BMS or DCB BRS DES/BMS or DCB

High Bleeding Risk High Bleeding Risk

No Yes No Yes
Time
AC AC AP A T AP A T AC A T
1mo 1mo DAPT Class IIb C or or
2 3
6mo DAPT 3mo DAPT Class IIa B
AC AC 6mo DAPT
3mo Class I A1 Class IIa B

≥12mo DAPT 12mo DAPT

6mo Class IIa C Class I A
AC
12mo DAPT >6mo
Class IIb A A T or A P A C
4

30mo >12mo DAPT

Class IIb B

Reference: Valgimigli M, et al. Eur Heart J. 2018; 39:213-260. A = Aspirin C = Clopidogrel P = Prasugrel T = Tricagrelor
 ANTITHROMBOTIC TREATMENT:
Dual antiplatelet therapy duration in patients with ACS (2) 3.2
P.42
CABG Medical Treatment Alone

Treatment Stable CAD ACS Stable CAD ACS

indication

Device used No indication No indication

for DAPT unless for DAPT unless
concomitant or concomitant or
prior indication High Bleeding Risk prior indication High Bleeding Risk
overrides No Yes overrides No Yes
Time
3
AP A T AC A T A T AC AC
1mo or or
3
AC 6mo DAPT >1mo DAPT
3mo Class IIa C Class IIa C
12mo DAPT 12mo DAPT
6mo Class I C Class I C

12mo
A T or A T or A C
30mo AP AC
>12mo DAPT >12mo DAPT
Class IIb C Class IIb C

Reference: Valgimigli M, et al. Eur Heart J. 2018; 39:213-260. A = Aspirin C = Clopidogrel P = Prasugrel T = Tricagrelor
 ANTITHROMBOTIC TREATMENT:
Switching between P2Y12 inhibitors for DAPT after ACS (1) 3.2
P.43

CLOPIDOGREL

irr
l
re

Ti ct in
os lop g)

es t
og

ca ic g
dd rc m

pe im
ing id

gr e o an
an prio (60

elo f p d d
r L rio os
ing of LD

Cl aft

D r c ing
24
tim tice rel

el g)

op er

(18 lo
se

h
gr m
c g

ido la
do
pe su

0 pid
su 0

gr st
es Pra

mg og
ra 60

el tic
tp (

) rel
LD ag
as LD

(6 relo
r l el
irr

00 r
fte og
h a pid

mg dos
ACCUTE SETTING
24 Clo

) e
ALWAYS RELOAD

Ticagrelor LD (180 mg)

24h after last prasugrel dose
PRASUGREL TICAGRELOR

Prasugrel LD (60 mg)

24h after last ticagrelor dose

Reference: Valgimigli M, et al. Eur Heart J. 2018;39:213-260.

 ANTITHROMBOTIC TREATMENT:
Switching between P2Y12 inhibitors for DAPT after ACS (2) 3.2
P.44

CLOPIDOGREL

Tr h a
el .)

24
ica fte
se
gr q.d
do

gr r l
ido mg

elo as
r M t cl
lop 0

do .)
t c (1

el .d

D pi
se
as D

Cl aft
gr g q

24

(9 do
rl lM

op er
su m

0 gr
h

o
fte gre

ido la

mg el
ra 5
t p (7

gr st
h a su

b.i dos
el tic
as D
24 Pra

rl lM

.d. e
LD ag

)
fte gre

(6 relo
h a do

00 r
i

CHRONIC
24 op

mg dos
Cl

) e
SETTING

Ticagrelor LD (90 mg b.i.d.)

PRASUGREL 24h after last prasugrel dose TICAGRELOR

Prasugrel LD (60 mg)

24h after last ticagrelor dose

Reference: Valgimigli M, et al. Eur Heart J. 2018;39:213-260.

 ANTITHROMBOTIC TREATMENT:
Risk scores validated for DAPT duration decision-making 3.2
P.45
PRECISE-DAPT score DAPT score
Time of use At the time of coronary stenting After 12 months of uneventful DAPT
DAPT duration Short DAPT (3-6 months) Standard DAPT (12 months)
strategies assessed vs. Standard/long DAPT (12-24 monts) vs. Long DAPT (30 months)
Score calculation Age
HB
≥75 — 2  pt
65 to <75 — 1  pt
WBC <65 0 pt
Cigarette smoking + 1  pt
Age
Diabetes mellitus + 1  pt
MI at presentation + 1  pt
CrCl
Prior PCI or prior MI + 1  pt
Prior Paclitaxel-eluting stent + 1  pt
Bleeding Stent diameter <3 mm + 1  pt
Score CHF or LVEF <30% + 2  pt
Points Vein graft stent + 2  pt

Score range 0 to 100 points — 2 to 10 points

Decision making Score ≥25 → Short DAPT Score ≥2 → Long DAPT
cut-off Score <25 → Standard/long DAPT Score <2 → Standard DAPT
Electronic calculator www.precisedaptscore.com www.daptstudy.org
 ANTITHROMBOTIC TREATMENT in patients with concomitant
indication for DAPT and chronic oral anticoagulation (1) 3.2
P.46
• HIGH RISK OF BLEEDING?
*
In case of
High HAS-BLED: Hypertension, abnormal liver/renal function, prior stroke, bleeding diathesis, labile INR if on VKA, age >65, drugs selecting
assessment
Patient risk

dual therapy
STEP 1:

(e.g. NSAIDs or antiplatelets), alcohol abuse, ABC score: Age, Biomarkers (GDF-15, hs cTnT, Hb) and Clinical history of prior bleeding
• HIGH RISK OF RECURRENT CORONARY ISCHEMIC EVENTS? immediately after
ACS at presentation, prior ST, stenting of last remaining vessel, CrCL <60 ml/min, ≥3 stents implanted or lesions treated, stent implantation
bifurcation with 2 stents, overall stentlengh >60 mm, treatment of CTO clopidogrel should
be selected as
single antiplatelet
OAC: • NOAC* (preferable) agent. Aspirin
DUAL SAPT: • Clopidogrel 75 mg q.d. - Apixaban 5 mg b.i.d. (reduce to 2.5 mg b.i.d. (1) should however
THERAPY (preferable)* - Dabigatran 110 mg b.i.d. (preferable while on DAPT) be administered
Treatment type

or or 150 mg b.i.d. at the time of the

STEP 2:

- Edoxaban 60 mg q.d. (reduce to 30 mg q.d. (2)

(If High BR Low IR)
TRIPLE DAPT: • Clopidogrel 75 mg q.d.
THERAPY
(If High BR High IR)
or
(If Low BR High IR)
Treatment duration
• Aspirin 75-100 mg q.d. intervention.
- Rivaroxaban 20 mg q.d. (reduce to 15 mg q.d. (3) or 15 mg
(may be considered DAPT/SAPT)
or Age ≥80 years,
(1) 
and • VKA dose ajusted: consider maintaining INR in the lower body weight ≤60 kg
• Aspirin 75-100 mg q.d. part of the recommended target range (e.g. 2.0-2.5 for AF or serum creatinine
and MV in aortic position, 2.5-3.0 for MV in mitral position)
level ≥1.5 mg/dL.
(2) 
CrCl of
30–50 ml/min,

DUAL THERAPY strategy: DUAL (12 mo.) OAC alone

body weight
≤60 kg,
STEP 3:

BR>IR TRIPLE (for 1 mo.) DUAL (up to 12 mo.) OAC alone concomitant use
TRIPLE THERAPY strategy: of verapamil,
DUAL quinidine or
BR<IR TRIPLE (up to 6 mo.) (up to 12 mo.) OAC alone dronedarone.
(3) 
CrCl 30-49 ml/min.

Reference adapted from Valgimigli M et al. Eur Heart J. 2018;39:213-260.

 ANTITHROMBOTIC TREATMENT:
Management of DAPT after ACS in patients 3.2
with indication for surgery P.47

PRASUGREL PRASUGREL(2)
STOP
CLOPIDOGREL SURGERY CLOPIDOGREL
STOP
TICAGRELOR TICAGRELOR(2)
STOP
ASPIRIN(1)

//••••••9••••••8••••••7••••••6••••••5••••••4••••••3••••••2••••••1•••••• 0••••••••••••••••••1-4

Minimal delay for P2Y12 interruption Days after surgery

= Expected average platelet function recovery

Decision to stop aspirin throughout surgery should be made on a single case basis taking into account the surgical bleeding risk
(1) 

In patients not requiring OAC

(2) 

Reference: Valgimigli et al. Eur Heart J.2018; 39:213-260.

 ANTITHROMBOTIC TREATMENT:
Management of acute bleeding after ACS
ANTITHROMBOTIC TREATMENT LIFE-THREATENING BLEEDING
e.g. massive overt genitourinary,
MANAGEMENT DURING BLEEDING respiratory or upper/lower
gastrointestinal bleeding,
Active bleeding and unstable hemodynamic active intracranial, spinal
putting patient’s life immediately at risk? Yes or intraocular haemorrhage,
or any bleeding
No
SEVERE BLEEDING
e.g. severe genitourinary,
Hospitalization required? Hb loss >5 g/dl respiratory or upper/lower
Yes
gastrointestinal bleeding
Hb loss <5 g/dl
MODERATE BLEEDING
No e.g. genitourinary, respiratory
or upper/lower gastrointestinal
bleeding with significant blood
Significant blood loss (>3 g/dl) ? loss or requiring transfusion
Yes
No MILD BLEEDING
e.g. not self resolving epistaxis,
moderate conjunctival bleeding,
Requires medical intervention genitourinary or upper/lower
or further evaluation? Yes gastrointestinal bleeding
without significant blood loss,
mild haemoptysis
No
TRIVIAL BLEEDING e.g. skin bruising or ecchimosis,
self-resolving epistaxis, minimal conjunctival bleeding
3.2
P.48
STOP ALL ANTITHROMBOTIC MEDICATIONS
and reverse OAC. Once bleeding has ceased, re-evaluate the need
for DAPT or SAPT, preferably with the P2Y12 inhibitor
especially in case of upper GI bleeding
CONSIDER STOPPING DAPT
and continue with SAPT, preferably with the P2Y12 inhibitor
especially in case of upper GI bleeding. Once bleeding has ceased,
re-evaluate the need for DAPT or SAPTa
CONSIDER STOPPING OAC
or even reversal until bleeding is controlled, unless prohibitive thrombotic risk
(i.e. mechanical heart valve in mitral position, cardiac assist device )b-c-d
Reinitiate treatment within one week if clinically indicated.
If Bleeding persist despite treatment, or treatment is not possible
CONSIDER STOPPING ALL ANTITHROMBOTIC MEDICATIONS
CONSIDER STOPPING DAPT
and continue with SAPT, preferably with the P2Y12 inhibitorespecially in case
of upper GI bleeding Reinitiate DAPT as soon as deemed safea
CONSIDER STOPPING OAC
or even reversal until bleeding is controlled, unless very high thrombotic risk
(i.e. mechanical heart valves, cardiac assist device, CHA2DS2-VASc ≥4 ).b-c-d
Reinitiate treatment within one week if clinically indicated.
CONTINUE DAPT a , CONTINUE OAC c
CONTINUE DAPT, CONTINUE OAC Consider skipping one single next pill

a
Consider shortening DAPT duration or switching to less potent P2Y12 inhibitor (i.e. from ticagrelor/prasugrel to clopidogrel), especially if recurrent bleeding occurs
Reinitiate treatment within one week if clinically indicated. For Vitamin-K antagonist consider a target INR of 2.0-2.5 unless overriding indication (i.e. mechanical
b 

heart valves or cardiac assist device) for NOAC consider the lowest effective dose. - c In case of triple therapy consider downgrading to dual therapy, preferably with
clopidogrel and OAC. - d If patients on dual therapy, consider stopping antiplatelet therapy if deemed safe.
Reference: Valgimigli et al. Eur Heart J.2018; 39:213-260.
 ANTITHROMBOTIC TREATMENT:
Management of antiplatelet therapy after acute GI bleeding 3.2
P.49

Acute upper GI haemorrhage in patient using antiplatelet agent(s) (APT)

Upper GI endoscopy demonstrates a nonvariceal source of bleeding (e.g. peptic ucler bleed)

High risk endoscopic stigmata identified Low risk endoscopic stigmata identified
(Forrest classification* Ia, Ib, IIa, IIb) (Forrest classification* IIc, III)

APT used for secondary prophylaxis APT used for secondary prophylaxis
(known cardiovascular disease) (known cardiovascular disease)

Patients on low dose ASA alone
• Resume low-lose ASA by day 3 following in dex endoscopy
• Second-look endoscopy at the discretion
of the endoscopist may be considered
Paptients on dual antiplatelet therapy (DAPT)
• Continue low dose ASA without interruption
• Early cardiology consultation for recommendation
of second resumption/ continuation of second APT
• Second-look endoscopy at the discretion of the
endoscopoist may be considered
Patients on low dose ASA alone
• Continue low-dose ASA without interruption
Paptients on dual antiplatelet therapy (DAPT)
• Continue DAPT without interruption
*The Forrest classification in defined as follows: Ia spuring
hemorrhage, Ib oozing hemorrhage, IIa nonbleeding visible
vessel, IIb an adherent clot, IIc flat pigmented spot, and III clean
base ucler.
Reference: Halvorsen et al. Eur Heart J 2017; 38: 1455-62.
 4

CHAPTER 4
ACUTE HEART FAILURE

4.1 WET-AND-WARM HEART FAILURE PATIENT ������������������������������ p.52

V.P. Harjola, O. Miró

4.2 CARDIOGENIC SHOCK (WET-AND-COLD) ����������������������������������� p.61

P. Vranckx, U. Zeymer
 Clinical profiles of patients with acute heart failure 4.1
Clinical profiles of patients with acute heart failure P.52
based on the presence/absence of congestion and/or hypoperfusion

CONGESTION (-) CONGESTION (+)

Pulmonary congestion, orthopnoea/paroxismal,
nocturnal dyspnoea, peripheral (bilateral) oedema,
jugular venous dilatation, congested hepatomegaly,
gut congestion, ascites, hepatojugular reflux

HYPOPERFUSION (-) WARM-DRY WARM-WET

HYPOPERFUSION (+)
Cold sweaty extremities, Oliguria,
COLD-DRY COLD-WET
Mental confusion, Dizziness,
Narrow pulse pressure

Hypoperfusion is not synonymous with hypotension, but often hypoperfusion is accompanied by hypotension.

Reference: Ponikowski P et al. Eur J Heart Fail. 2016; 18(8):891-975. DOI: 10.1002/ejhf.592.
 ACUTE HEART FAILURE: Diagnosis and causes (2)
1 Symptoms: Dyspnea (on effort or at rest)/
breathlessness, fatigue, orthopnea, cough,
weight gain/ankle swelling.
2 Signs: Tachypnea, tachycardia, low or normal blood
pressure, raised jugular venous pressure,
3rd/4th heart sound, rales, oedema, intolerance
of the supine position.
3 Cardiovascular risk profile: Older age, HTN, diabetes,
smoking, dyslipidemia, family history, history of CVD.
4 Precipitants/causes that need urgent management
(CHAMP): Acute coronary syndrome. Hypertensive
emergency. Rapid arrhythmias or severe
bradyarrhythmia/conduction disturbance. Mechanical
causes. Pulmonary embolism.
5 Differential diagnosis: Exacerbated pulmonary disease,
pneumonia, pulmonary embolism, pneumothorax,
acute respiratory distress syndrome, (severe) anaemia,
hyperventilation (metabolic acidosis), sepsis/septic
shock, redistributive/hypovolemic shock.
Reference: McMurray JJ et al. Eur Heart J (2012); 33:1787-847.
Ponikowski P et al. Eur J Heart Fail. 2016; 18:891-975.
4.1
P.53
FACTORS TRIGGERING ACUTE HEART FAILURE
• Acute coronary syndrome
• Tachyarrhythmia (e.g. atrial fibrillation, ventricular tachycardia)
• Excessive rise in blood pressure
• Infection (e.g. pneumonia, infective endocarditis, sepsis).
• Non-adherence with salt/fluid intake or medications
• Toxic substances (alcohol, recreational drugs)
• Drugs (e.g. NSAIDs, corticosteroids, negative inotropic
substances, cardiotoxic chemotherapeutics)
• Exacerbation of chronic obstructive pulmonary disease
• Pulmonary embolism
• Surgery and perioperative complications
• Increased sympathetic drive, stress-related cardiomyopathy
• Metabolic/hormonal derangements (e.g. thyroid dysfunction,
diabetic ketosis, adrenal dysfunction, pregnancy and
peripartum related abnormalities)
• Cerebrovascular insult
• Acute mechanical cause : myocardial rupture complicating
ACS (free wall rupture, ventricular septal defect, acute
mitral regurgitation), chest trauma or cardiac intervention,
acute native or prosthetic valve incompetence secondary
to endocarditis, aortic dissection or thrombosis
 Initial management of a patient with ACUTE HEART FAILURE 4.1
Patient with suspected AHF P.54
Circulatory support
1. Cardiogenic shock ? • pharmacological
Urgent phase after Yes • mechanical
first medical contact No
2. Respiratory failure ? Ventilatory support
Yes • oxygen
No • non-invasive positive
pressure ventilation (CPAP, BiPAP)
• mechanical ventilation

Immediate phase Immediate stabilization

(initial 60-120 minutes) and transfer to ICU/CCU

Indentification of acute aeticology :

C = Acute Coronary syndrome
H = Hypertension emergency
A = Arrhythmia
M = Acute Mechanical cause
P = Pulmonary embolism

No Yes Immediate initiation

of specific treatement
Diagnostic work-up to confirm AHF
Clinical evaluation to select optimal management

Reference: Ponikowski P et al. Eur J Heart Fail. 2016; 18(8): 891-975. DOI: 10.1002/ejhf.592.
 ACUTE HEART FAILURE: Airway (A) and breathing (B)
Oxygen therapy and ventilatory support in acute heart failure 4.1

Upright position P.55

Pre-hospital or
emergency room No RESPIRATORY DISTRESS? Yes
SpO2 <90%, RR>25,
Work of breathing, orthopnea

Conventional oxygen therapy CPAP

Intubation

In hospital No
"PERSISTENT" RESPIRATORY DISTRESS?
Yes
Venous/Arterial blood gases

SIGNIFICANT HYPERCAPNIA NORMAL pH

AND ACIDOSIS AND pCO2

Conventional Intolerance
oxygen therapy PS-PEEP CPAP
Intubation
After Weaning
60-90 min SUCCESS FAILURE
Room air

Reference adapted from Mebazaa A et al. Eur J Heart Fail. (2015); 17:544-58.
 ACUTE HEART FAILURE: Initial diagnosis (CDE) 4.1
P.56
C - CIRCULATION *

HR (bradycardia [<60/min], normal [60-100/min], tachycardia [>100/min]), rhythm (regular, irregular), SBP (very low
[<90 mmHg], low, normal [110-140 mmHg], high [>140 mmHg]), and elevated jugular pressure should be checked.

INSTRUMENTATION & INVESTIGATIONS: ACTIONS:

Intravenous line (peripheral/central) and BP monitoring (arterial line in shock
and severe ventilatory/gas-exchange disturbances) Rule in/out
Laboratory measures acute heart failure
• Cardiac markers (troponin, BNP/NT-proBNP/MR-proANP) as cause of symptoms
•C omplete blood count, electrolytes, creatinine, urea, glucose, and signs
inflammation, TSH
•C onsider arterial or venous blood gases, lactate, D-dimer Determine
(suspicion of acute pulmonary embolism)  clinical profile
Standard 12-lead ECG
• Rhythm, rate, conduction times? Start as soon as
• Signs of ischemia/myocardial infarction? Hypertrophy? possible treatment of
Echocardiography both heart failure and
a) Immediately in haemodynamically unstable patients the factors identified
b) W ithin 48 hours when cardiac structure and function are either not known or as triggers
may have changed since previous studies
Establish cause
Ventricular function (systolic and diastolic)? Estimated left-and right-side filling
pressures? Lung ultrasound? Presence of valve dysfunction (severe stenosis/
insufficiency)? Pericardial tamponade?
 4.1
P.57

D – DISABILITY DUE TO NEUROLOGICAL DETERIORATION

• Normal consiousness/altered mental status?
Measurement of mental state with AVPU (alert, visual, pain or unresponsive) o
 r Glasgow
• Coma Scale: EMV score <8 Consider endotracheal intubation and mechanical ventilation
• Anxiety, severe dyspnea? Consider cautious administration of morphine 2 mg i.v. bolus,
preceded by antiemetic as needed

E – EXPOSURE & EXAMINATION

• Temperature/fever: central and peripheral
• Weight
• Skin/extremities: circulation (e.g. capilary refill), color
• Urinary output (<0.5 ml/kg/hr) Consider inserting indwelling catheter;
the benefits should outweigh the risks of infection and long-term complications

References: Mebazaa A et al. Intensive Care Med. (2016); 42(2):147-63; Mueller C et al. Eur Heart J Acute Cardiovasc Care. (2017); 6(1):81-6.
ACUTE HEART FAILURE: Management of patients with acute heart
failure based on clinical profile during an early phase 4.1
P.58

Patient with AHF

Bedside assessment to identify haemodynamic profiles

PRESENCE OF CONGESTIONa?

Yes No
(95% of all AHF patients) (5% of all AHF patients)

"WET" patient "DRY" patient

ADEQUATE PERIPHERAL PERFUSION?

Yes Yes No

"DRY" and "WARM" "DRY" and "COLD"

"WET" and "WARM"
patient (typically elevated
or normal systolic blood
pressure)
Adequately perfused Hypoperfused, hypovolemic
No ≈ Compensated
Consider fluid challenge
Adjust oral therapy Consider inotropic agent if still hypoperfused
 4.1
P.59

"WET" and "COLD" patient

Systolic blood pressure <90 mmHg

Yes No
Vascular type-fluid Cardiac type-fluid
redistribution accumulation
Hypertension predominates Congestion predominates
• Inotropic agent • Vasodilators
• Consider vasopressor • Diuretics
in refractory cases • Consider inotropic agent
• Vasodilator • Diuretic • Diuretic In refractory cases
• Diuretic • Vasodilator (when perfusion corrected)
• Ultrafiltration • Consider machanical circulatory
(consider if diuretic resistance) support if no response to drugs

Symptoms/signs of congestion: orthopnoea, paroxysmal nocturnal dyspnoea, breathlessness, bi-basilar rales, abnormal blood pressure response to the
a 

Valsalva maneuver (left-sided); symptoms of gut congestion, jugular venous distension, hepatojugular reflux, hepatomegaly, ascites, and peripheral
oedema (right-sided).

For more information on individual drug doses and indications,

SEE CHAPTER 9 DRUGS USED IN ACUTE CARDIOVASCULAR CARE

Reference: Ponikowski P et al. Eur J Heart Fail. 2016; 18(8):891-975. DOI: 10.1002/ejhf.592.
 ACUTE HEART FAILURE: Management of acute heart failure 4.1
P.60
DIAGNOSTIC TESTS
OBSERVATION UP TO 120 min

No acute heart failure Confirmed acute heart failure

MONITORING TREATMENT OBJECTIVES to prevent organ dysfunction:

Dyspnea (VAS, RR), BP, SpO2, HR and Improve symptoms, maintain SBP >90 mmHg and peripheral
rhythm, urine output, peripheral perfusion perfusion, mantain SpO2 >90% (see table in pages 63-64)

REASSESSMENT
Clinical, biological and psychosocial parameters by trained nurses
ADMISSION/DISCHARGE

Observation unit (<24h) Ward (cardiology, internal ICU/CCU

medicine, geriatrics)
Risk stratification: ensure patient
is at low risk before direct discharge

Discharge home

Visit to cardiologist Rehabilitation Palliative care

<1-2 weeks program hospitals
Reference adapted from Mebazaa A et al. Eur J Heart Fail. (2015); 17: 544-58 and Miró Ò et al. Ann Intern Med (2017); 167:698-705.
 ACUTE HEART FAILURE: Treatment (C) and preventive measures 4.0
4.1
Management of oral therapy in AHF in the first 48 hours P.61

Normotension/ Hypotension Low heart rate Potassium Renal impairment

Hypertension <100 >90 <90 <60 <50 bpm ≤3.5 >5.5 Cr <2.5, Cr >2.5,
mmHg mmHg ≥50 bpm mmol/L mmol/L eGFR >30 eGFR <30

ACE-I/ARB Review/ Reduce/ Stop No No Review/ Stop Review Stop

increase stop change change increase
Beta-blocker No change Reduce/ Stop Reduce Stop No No No No
stop change change change change
MRA No change No Stop No No Review/ Stop Reduce Stop
change change change increase
Diuretics Increase Reduce Stop No No Review/ Review/ No Review
change change No increase change
change
Sacubitril/ Review/ Stop Stop No No Review/ Stop Review Stop
Valsartan increase change change increase

Reference adapted from Mebazaa A et al. Eur J Heart Fail. (2015); 17(6):544-58.
 ACUTE HEART FAILURE: Treatment (C) and preventive measures (Cont.) 4.1
Management of oral therapy in AHF in the first 48 hours P.62

Normotension/ Hypotension Low heart rate Potassium Renal impairment

Hypertension <100 >90 <90 <60 <50 bpm ≤3.5 >5.5 Cr <2.5, Cr >2.5,
mmHg mmHg ≥50 bpm mmol/L mmol/L eGFR >30 eGFR <30

Other Increase Reduce/ Stop No No No No No No

vasodilators stop change change change change change change
(nitrates)

Other heart rate Review Reduce/ Stop Reduce/ Stop Review/ No No No

slowing drugs stop stop stop(*) change change change
(amiodarone,
non-dihydropyridine
CCB, ivabradine)

Thrombosis prophylaxis should be started in patients not anticoagulated.

(*) Amiodarone.

Reference adapted from Mebazaa A et al. Eur J Heart Fail. (2015); 17(6):544-58.

 CARDIOGENIC SHOCK: Definition 4.2
P.63
Clinical condition defined as the inability of the heart to deliver an adequate amount of blood
to the tissues to meet resting metabolic demands as a result of impairment of its pumping function.
Cardiogenic shock is equal to wet-cold phenotype. The clinical signs of hypoperfusion are listed in page 65.
In addition, blood lactate is typically elevated above 2 mmol/L.

Hemodynamic criteria to define cardiogenic shock

• Systolic blood pressure <80 to 90 mmHg

or mean arterial pressure 30 mmHg lower than baseline

• Severe reduction in cardiac index:

<1.8 l/min/m2 without support
or <2.0 to 2.2 l/min/m2 with support

• Adequate or elevated filling pressure:

Left ventricular end-diastolic pressure >18 mmHg
or Right atrial pressure >10 to 15 mmHg
 CARDIOGENIC SHOCK: Causes
4.2
LV pump failure is the primary insult in most forms of CS, but other parts of the circulatory system
contribute to shock with inadequate compensation or additional defects P.64
 CARDIOGENIC SHOCK: Initial triage and management
This protocol should be initiated as soon as cardiogenic shock/end organ hypoperfusion is recognised
and should not be delayed pending intensive care admission.
EARLY TRIAGE & MONITORING
EMERGENCY DEPARTMENT
0 min Start high flow O2
Establish i.v. access
5 min
INITIAL RESUSCITATION
•A
 rterial and a central venous
catheterization with a catheter
15 min capable of measuring central venous
CARDIAC INTENSIVE CARE UNIT
oxygen saturation
•S
 tandard transthoracic
echocardiogram to assess left (and
right) ventricular function and for
the detection of potential mechanical
complications following MI
60 min •E
 arly coronary angiography in
specialized myocardial intervention
centre when signs and/or symptoms
of ongoing myocardial ischemia
(e.g. ST-segment elevation myocardial
infarction).
4.2
P.65
• Age: 65–74, ≥75
• Heart rate >100 beats per minute
• Systolic blood pressure <100 mmHg
• Proportional pulse pressure ≤25 % (CI <2.2 l/min/m2)
• Orthopnea (PCWP >22 mmHg)
• Tachypnea (>20/min), >30/min (!)
• Killip class IV
•C linical symptoms of tissue hypoperfusion/hypoxia:
- cool extremities - decreased urine output (urine output <40 ml/h)
- decreased capillary refill or mottling - alteration in mental status
• CORRECT: hypoglycemia & hypocalcemia,
• TREAT: sustaned arrhythmias: brady- or tachycardia
• Isotonic saline-fluid challenge - 200-300 ml
over 30 min period to achieve a central venous pressure of 8 to 12 mmHg
or until perfusion improves (with a maximum of 500 ml)
• CONSIDER NIMV for comfort (fatigue, distress) or as needed:
- To correct acidosis - To correct hypoxemia
• INOTROPIC SUPPORT (dobutamine, levosimendan and/or vasopressor support)
TREATMENT GOALS
• a mean arterial pressure of 60 mmHg or above,
• a mean pulmonary artery wedge pressure of 18 mmHg or below,
• a central venous pressure of 8 to 12 mmHg,
• a urinary output of 0,5 ml or more per hour per kilogram of body weight
• an arterial pH of 7.3 to 7.5
• a central venous saturation (ScvO2) ≥70% (provided SpO2 ≥93%
and Hb level ≥9 g/dl)
In persistent drug-resistant cardiogenic shock,
consider mechanical circulatory support
 CARDIOGENIC SHOCK: Treatment and ventilator procedures 4.2
P.66
For more informations on individual drug doses and indications:

Ventilator mode Pressure assist/control

Tidal Volume goal Reduce tidal volume to 6-8 ml/kg lean body weight
Plateau Pressure goal ≤30 cm H2O
Anticipated PEEP levels 5-10 cm H2O
Ventilator rate and pH goal 12-20, adjusted to achieve a pH ≥7.30 if possible
Inspiration: Expiration time 1:1 to 1:2
Oxygenation goal:
• PaO2 50-80 mmHg
• SpO2 >90%

Predicted body weight calculation:

• Male: 50 + 0.91 (height in cm - 152.4)
• Female: 45.5 + 0.91 (height in cm - 152.4)

Some patients with CS will require increased PEEP to attain functional residual capacity and maintain oxygenation,
and peak pressures above 30 cm H2O to attain effective tidal volumes of 6-8 ml/kg with adequate CO2 removal.

For more information on individual drug doses and indications,

SEE CHAPTER 9 DRUGS USED IN ACUTE CARDIOVASCULAR CARE
 CARDIOGENIC SHOCK:MANAGEMENT
CARDIOGENIC SHOCK: managementFOLLOWING
following STEMI
STEMI 4.2
P.67
Assess volume status
Treat sustained arrhythmias: brady - or tachy -
Consider mechanical ventilation for comfort (during PCI) and/or as needed:
• to correct acidosis
• to correct hypoxemia
Inotropic support (dobutamine and/or vasopressor support)

Signs (ST-segment elevation or new LBBB) Emergency echocardiography

and/or clinical symptoms of ongoing No ± Tissue doppler imaging
myocardial ischemia NSTEACS, ± Color flow imaging
Delayed CS
Yes

Early coronary angiography Pump failure • Acute severe mitral valve regurgitation Aortic
± Pulmonary artery catheter RV, LV, both • Ventricular septum rupture dissection
Short-term mechanical

± IABP in selected patients • Severe aortic/mitral valve stenosis Pericardial

circulatory support

in a specialised Myocardial tamponade

Intervention Centre

Operating theater ± coronary angiography

PCI ± stenting CABG

of the culprit lesion + correct mechanical complications
 CARDIOGENIC SHOCK:
Mechanical circulatory support, basic characteristics 4.2
P.68

1-month ...
2-weeks

72-hrs
IABP Impella 2.5 Impella 5.0 Tandem- Levitronix ECMO Implantable
heart
Left ventricular support BiVentricular support

Partial support Full support

Pulmonary support

Level of support
 4.2
P.69
Type Support Access
Intra-aortic balloon Balloon Pulsatile flow <0.5 L Arterial: 7.5 French
pump counterpulsation
Impella Recover Axial flow Continuous flow
 LP 2.5  <2.5 L Arterial: 12 French
 CP  <4.0 L Arterial: 14 French
 LP 5.0  <5.0 L Arterial: 21 French
Tandemheart  <5.0 L Venous: 21 French
Arterial: 15-17 French
Cardiohelp Centrifugal flow Continuous flow
Venous: 15-29 French
 <5.0 L Arterial: 15-29 French

Different systems for mechanical circulatory support are available to the medical community.
The available devices differ in terms of the insertion procedure, mechanical properties, and
mode of action. A minimal flow rate of 70 ml/kg/min, representing a cardiac index of at least
2.5 L/m2, is generally required to provide adequate organ perfusion. This flow is the sum
of the mechanical circulatory support output and the remaining function of the heart.

The SAVE-score may be a tool to predict survival for patients receiving ECMO for refractory
cardiogenic shock (www.save-score.com).
 5
P.71
CHAPTER 5
CARDIAC ARREST AND
CARDIOPULMONARY RESUSCITATION
N. Nikolaou, L. Bossaert

THE CHAIN OF SURVIVAL

Monsieurs KG, et al. European Resuscitation Council Guidelines for Resuscitation 2015. Section 1
Executive Summary. Resuscitation 2015; 95C:1-80, DOI:10.1016/j.resuscitation.2015.07.038
 OUT
OUT OF HOSPITAL
OF HOSPITAL CARDIAC
CARDIAC ARREST: ARREST:
Assessment
ASSESSMENT of a collapsed
OF A COLLAPSED VICTIMvictim andTREATMENT
AND INITIAL initial treatment 5
P.72
VICTIM COLLAPSES

Approach safely
Check response
Victim responds
Victim unresponsive

Leave victim as found

Find out what is wrong Shout for help
Reassess victim regularly Open airway
Assess breathing
Breathing normally

Put victim in recovery position Not breathing normally

and call for an ambulance
Call for an ambulance
Start CPR 30:2
Send or go for an AED
AED not available

30 chest compressions: As soon as AED arrives

2 rescue breaths
Start AED,
listen to and follow voice prompts

AED Assesses rhythm

 5
P.73
Shock advised No shock advised

1 shock Immediately resume

CPR 30:2 for 2 min
Immediately resume
CPR 30:2 for 2 min

Continue until victim starts to wake up: to move, open eyes, and breathe normally
 IN-HOSPITAL
IN-HOSPITAL CARDIAC ARREST:
CARDIAC ARREST:
Assessment 5
ASSESSMENT OFofAaCOLLAPSED
collapsed victim and INITIAL
VICTIM AND initial treatment
TREATMENT
P.74

Collapsed/sick patient

Shout for HELP & assess patient

No Signs of life? Yes

Call resuscitation
team
Assess ABCDE
Recognise & treat
oxygen; monitoring, i.v. access
CPR 30:2
with oxygen and airway adjuncts
 5
Apply pads/monitor Call resuscitation team P.75
Attempt defibrillation if appropriate
if appropriate

Advanced Life Support Handover to resuscitation team

when resuscitation team arrives
 IN-HOSPITAL
IN-HOSPITAL CARDIAC ARREST:
CARDIAC ARREST: Advanced
ADVANCED life
LIFE support
SUPPORT 5
P.76
Unresponsive
and not breathing
normally ?

Call resuscitation
team

CPR 30:2
Attach defibrillator/monitor
Minimise interruptions

Assess
rhythm

Shockable Non-shockable
(VF/Pulseless VT) (PEA/Asystole)

1 Shock
Immediately resume:
CPR for 2 min
Minimise interruptions
DURING CPR
• Ensure high-quality
chest compressions
• Minimise interruptions
to compressions
• Give Oxygen
• Use waveform capnography
• Continuous chest compressions
when advanced airway in place
• Vascular access (intravenous,
intraosseous)
• Give adrenaline every 3-5 min
• Give amiodarone after 3 shocks
• Correct reversible causes
5
Return of
P.77
spontaneous circulation
Immediately resume:
IMMEDIATE POST CPR for 2 min
CARDIAC Minimise interruptions
ARREST TREATMENT
• Use ABCDE approach
• Aim for SaO2 94-98%
• Aim for normal PaCO2 REVERSIBLE CAUSES
• 12-lead ECG • Hypoxia
• Treat precipitating cause • Hypovolaemia
• Temperature control / • Hypo-/hyperkalaemia/metabolic
• Hypothermia
Therapeutic hypothermia
• Thrombosis
CONSIDER • Tamponade - cardiac
• Ultrasound imaging • Toxins
• Mechanical chest • Tension pneumothorax
compressions to facilitate
transfer/treatment
• Coronary angiography
and PCI
• Extracorporeal CPR
 IN-HOSPITAL CARDIAC ARREST:
Drug therapy during advanced life support 5
P.78
IN-HOSPITAL CARDIAC ARREST: DRUG THERAPY DURING ADVANCED LIFE SUPPORT
Cardiac Arrest

Shockable rhythm Non-shockable

(VF, pulseless VT) rhythm

Give adrenaline and amiodarone Adrenaline: 1mg i.v. (10 ml 1:10,000 or 1 ml 1:1000)
after 3rd shock given as soon as circulatory access is obtained
Repeat every 3-5 min (alternate loops)
Give without interrupting chest compressions

Adrenaline: 1 mg i.v. Amiodarone

(10 ml 1:10,000 or 1 ml 1:1000) 300 mg bolus i.v.
repeated every 3-5 min Second bolus dose of 150 mg i.v.
(alternate loops) if VF/VT persists
given without interrupting followed by infusion of
chest compressions 900 mg over 24 h
 6

CHAPTER 6
RHYTHM DISTURBANCES

6.1 SUPRAVENTRICULAR TACHYCARDIAS AND ATRIAL FIBRILLATION ���� p.80

J. Brugada

6.2 VENTRICULAR TACHYCARDIAS ������������������������������������������ p.84

M. Santini, C. Lavalle, S. Lanzara

6.3 BRADYARRHYTHMIAS ���������������������������������������������������� p.87

B. Gorenek
 TACHYARRHYTHMIAS: Diagnostic criteria 6.1
TACHYARRHYTHMIAS: DIAGNOSTIC CRITERIA
Tachycardia
P.80
>100 beats/min

Regular Irregular

QRS morphology similar to QRS morphology QRS morphology similar to QRS morphology
in sinus rhythm? in sinus rhythm?

YES NO YES NO

QRS complex QRS complex QRS complex QRS complex QRS complex QRS complex Variable QRS
<120 msec >120 msec <120 msec >120 msec <120 msec >120 msec morphology

Supraventr. Supraventr. Fascicular Ventricular AF AF + BBB AF Irregular

Tachycardia Tachycardia Tachycardia Tachycardia conducting or + Ventricular
+ BBB or SVT with or SVT with over AVN AF + WPW WPW Tachycardia
aberrant aberrant
conduction conduction
 TACHYARRHYTHMIAS: Diagnostic maneuvers 6.1
P.81
Regular tachycardia

Vagal maneuvers
or
i.v. adenosine

Tachycardia AV relation No change

terminates changes

More As More Vs Wide Narrow

than Vs than As QRS complex QRS complex

• Concordant precordial pattern

(all leads + or all leads –) Typical
• No RS pattern in precordial leads morphology
• RS pattern with beginning in V1 & V6
of R wave to nadir Consider
of S wave >100 msec Sinus tachycardia
or non proper
Consider administration
SVT using Atrial flutter of adenosine
the AV node or atrial Ventricular Ventricular Ventricular (too slow, insufficient
(AVNRT, AVNT) tachycardia Tachycardia Tachycardia Tachycardia dose, etc)
 TACHYARRHYTHMIAS: Therapeutic algorithms (1) 6.1
TACHYARRHYTHMIAS:
TACHYARRHYTHMIAS:
THERAPEUTIC
THERAPEUTIC
ALGORITHMS
ALGORITHMS
(1) (1) P.82
Regular
Regular
Supraventricular
Supraventricular
Tachycardias
Tachycardias Irregular
Irregular
and narrow
and narrow
QRS complex
QRS complex
with or
with
without
or without
bundlebundle
branchbranch
block block Tachycardia
Tachycardia

Hemodynamically
Hemodynamically Hemodynamically
Hemodynamically Less than
Less48thanhours
48 hours Hemodynamically non-stable
Hemodynamically non-stable
non-stable
non-stable stablestable since since
initiation
initiation
AND AND Immediate electrical
Immediate electrical
hemodynamically
hemodynamically
stablestable Cardioversion
Cardioversion
Immediate
Immediate
electrical
electrical VagalVagal
maneuvers
maneuvers
cardioversion
cardioversion and/orand/or
i.v. Adenosine
i.v. Adenosine Cardioversion
Cardioversion If no cardioversion
If no cardioversion
Electrical
Electrical or pharmacological is considered:
or pharmacological rate control
is considered: rate control
using using
oral ororali.v. or i.v. flecainide
flecainide using using
betablockers
betablockers
or or
(only in
(only
normal
in normal
heart)heart) calcium calcium
antagonists,
antagonists,
or i.v. or i.v. vernakalant
vernakalant togethertogether
with proper
with proper
No termination
No termination Termination
Termination
anticoagulation, if required
anticoagulation, if required
Anticoagulation
Anticoagulation
is initiated
is initiated
using using
i.v. heparine
i.v. heparine

NarrowNarrow
QRS QRS Wide QRS
Wide QRS
complex
complex
tachycardia
tachycardia complex
complex
tachycardia
tachycardia More More
than 48
than hours
48 hours
OR OR
unknown
unknown
time oftime
initiation,
of initiation,
Reconsider
Reconsider
diagnosis:
diagnosis: Reconsider
Reconsider
the diagnosis
the diagnosis
of of AND AND
sinus sinus
tachycardia,
tachycardia, Ventricular
Ventricular
Tachycardia even even
Tachycardia Patient
Patient
chronically
chronically
anticoagulated
anticoagulated
atrial atrial
tachycardia
tachycardia if hemodynamically
if hemodynamically
stablestable OR OR
a TEEashowing
TEE showing
no thrombus
no thrombus
If no evidence:
If no evidence: Do not
Doadminister
not administer
Intravenous
Intravenous
verapamil
verapamil verapimil
verapimil Electrical
Electrical
or pharmacological
or pharmacological
Cardioversion
Cardioversion
 TACHYARRHYTHMIAS: Therapeutic algorithms (2) 6.1
P.83
TACHYARRHYTHMIAS: THERAPEUTIC ALGORITHMS (2)
Irregular and wide QRS complex Tachycardia

Hemodynamically More than 48 hours Less than 48 hours since initiation

non-stable
Immediate electrical
Cardioversion
If no cardioversion is considered:
rate control using betablockers or
calcium antagonists (only if VT and
AF+WPW is excluded), together
with proper anticoagulation
if required
or unknown initiation, AND
AND hemodynamically stable
patient chronically anticoagulated
or a TEE showing no thrombus Cardioversion
electrical or pharmacological
Electrical or pharmacological using oral or i.v. flecainide
Cardioversion (only in normal heart)
or i.v. amiodarone
Anticoagulation
is initiated using i.v. heparin
 VENTRICULAR TACHYSCARDIAS:
Diferential diagnosis of wide QRS tachyscardias 6.2
VENTRICULAR TACHYCARDIAS: DIFERENTIAL DIAGNOSIS OF WIDE QRS TACHYCARDIA
P.84

EKG signs of atrio-ventricular dissociation

Yes
1st Step Random P waves unrelated to QRS complexes
Capture beats / fusion beats / second degree V-A block

No

Concordant pattern in precordial leads Yes

2nd Step No RS morphology in any of the precordial leads VT
No

An interval >100 ms from the beginning of the Yes

3rd Step QRS complex to the nadir of S in a precordial lead

No

Morphology in precordial leads Morphology

in aVR lead
 6.2
P.85
RBBB morphology LBBB morphology Yes
Initial R wave
No
Yes Initial R wave
V1: qR, R, R’ V1: rsR’, RSR’ V6: R V1: rS; R >30 ms, V6: qR, QS
or q >40 msec
V6: rS,QS V6: qRs S nadir >60 ms,
notching of the No
S wave
Notch in the
Yes descending
Q wave limb

No

Yes
VT Aberrant conduction VT Vi/Vt ≤1

No

Aberrant conduction
 Management of wide QRS TACHYSCARDIAS 6.2
MANAGEMENT OF WIDE QRS TACHYCARDIAS
P.86
Hemodynamic Tolerance

Non-stable Stable

Pulseless With pulse Irregular rhythm Regular rhythm

ACLS Resuscitation algorithm • Sedation Differential Diagnosis Vagal maneuver

• Immediate high- energy or analgesia and/or
No
defibrillation (200 J biphasic • Synchronised Yes i.v. adenosine (push)
or 360 monophasic) cardioversion
• Resume CPR and continue AF with aberrant
100 to 200 J ventricular conduction
according to the ACLS algorithm (monophasic)
• β-blockers Interruption or
or 50-100 J slow down HR
Drugs used in the ACLS algorithm (biphasic) • i.v.
• Epinephrine 1 mg i.v./i.o. • Verapamil or diltazem No Yes
(repeat every 3-5 min)
• Vasopressin 40 i.v./i.o. Pre excited AF
Differential SVT
• Amiodarone 300 mg i.v./i.o. • Class 1 AADs Diagnosis
once then consider an additional (see chapter 6.1
150 mg i.v./i.o. dose Polymorphic VT page 81)
• Lidocaine 1-1.5 mg/kg first dose • Amiodarone
then 0.5-0-75 mg/kg i.v./i.o.
for max 3 doses or 3 mg/kg
Amiodarone 150 mg i.v.
• Magnesium loading dose 1-2 gr
(can be repeated up to
i.v./i.o. for torsade des pointes
a maximum dose of 2.2 g in 24 h)
Synchronised cardioversion
 BRADYARRHYTHMIAS: Definitions and diagnosis
Sinus node dysfunction
• Sinus bradycardia: It is a rhythm that originates
from the sinus node and has a rate of under 60 beats
per minute
• Sinoatrial exit block: The depolarisations that occur in
the sinus node cannot leave the node towards the atria
• Sinus arrest: Sinus pause or arrest is defined as the
transient absence of sinus P waves
on the ECG
6.3
P.87
Atrioventricular (AV) blocks
• First degree AV block: Atrioventricular impulse
transmission is delayed, resulting in a PR interval
longer than 200 msec
• Second degree AV block: Mobitz type I (Wenckebach
block): Progressive PR interval prolongation, which
precedes a nonconducted P wave
• Second degree AV block: Mobitz type II: PR interval
remains unchanged prior to a P wave that suddenly fails
to conduct to the ventricles
• Third degree (complete) AV block:
No atrial impulses reach the ventricle
 BRADYARRHYTHMIAS: Treatment (1) 6.3
P.88

• Rule out and treat any underlying causes of bradyarrhythmia

• Treat symptomatic patients only

For more information on individual drug doses and indications,

SEE CHAPTER 9 DRUGS USED IN ACUTE CARDIOVASCULAR CARE

Temporary transvenous pacing

Be Careful!
• Complications are common!
• Shall not be used routinely
• Use only as a last resource when chronotropic drugs are insufficient
• Every effort should be made to implant a permanent pacemaker
as soon as possible, if the indications are established.

Indications limited to:

• High-degree AV block without escape rhythm
• Life threatening bradyarrhythmias, such as those that occur during interventional
procedures, in acute settings such as acute myocardial infarction, drug toxicity.
 BRADYARRHYTHMIAS: Treatment (2)
Pacemaker therapies in sinus node dysfunction 6.3
P.89

Permanent pacemaker is indicated in the following settings:

• Documented symptomatic bradycardia, including frequent sinus pauses that produce symptoms
• Symptomatic chronotropic incompetence
• Symptomatic sinus bradycardia that results from required drug therapy for medical conditions

Permanent pacemaker is not recommended in the following settings:

• Asymptomatic patients
• Patients for whom the symptoms suggestive of bradycardia
have been clearly documented to occur in the absence of bradycardia
• Symptomatic bradycardia due to nonessential drug therapy
 BRADYARRHYTHMIAS: Treatment (3)
Pacemaker therapies in atrioventricular blocks 6.3
P.90

Permanent pacemaker therapy is indicated in the following settings regardless of associated symptoms:

• Third-degree AV block
• Advanced second-degree AV block
• Symptomatic Mobitz I or Mobitz II second-degree AV block
• Mobitz II second-degree AV block with a wide QRS or chronic bifascicular block
• Exercise-induced second- or third-degree AV block
• Neuromuscular diseases with third- or second-degree AV block
• Third- or second-degree (Mobitz I or II) AV block after catheter ablation or valve surgery
when block is not expected to resolve

Permanent pacemaker is not recommended in the following settings:

• Asymptomatic patients
• Patients for whom the symptoms suggestive of bradycardia have been clearly documented
to occur in the absence of bradycardia
• Symptomatic bradycardia due to nonessential drug therapy
 7

CHAPTER 7
ACUTE VASCULAR SYNDROMES

7.1 ACUTE AORTIC SYNDROMES ���������������������������������������������� p.92

A. Evangelista

7.2 ACUTE PULMONARY EMBOLISM ������������������������������������������ p.102

A. Torbicki
ACUTE AORTIC SYNDROMES: Concept and classification (1)
Types of presentation 7.1
P.92

Classic aortic dissection

Separation of the aorta media with presence
of extraluminal blood within the layers of the aortic wall.
The intimal flap divides the aorta into two lumina, the true and the false

Intramural hematoma (IMH)

Aortic wall hematoma with no entry tear
and no two-lumen flow
Penetrating aortic ulcer (PAU)
Atherosclerotic lesion penetrates
the internal elastic lamina of the aorta wall

Aortic aneurysm rupture

(contained or not contained)
 ACUTE AORTIC SYNDROMES: Concept and classification (2)
Anatomic classification and time course 7.1
P.93
DeBakey’s Classification
• Type I and Type II dissections both originate in the ascending aorta
In type I, the dissection extends distally to the descending aorta
In type II, it is confined to the ascending aorta
• Type III dissections originate in the descending aorta

Stanford Classification
De Bakey Type I Type II Type III
• Type A includes all dissections involving the ascending
aorta regardless of entry site location
• Type B dissections include all those distal to the
brachiocephalic trunk, sparing the ascending aorta

Time course
• Acute: <14 days
• Subacute: 15-90 days
• Chronic: >90 days
Stanford Type A Type A Type B
Adapted with permission from Nienaber CA, Eagle KA,
Circulation 2003;108(6):772-778. All rights reserved.

Copyright: Nienaber CA, Eagle KA. Aortic dissection: new frontiers in diagnosis and management: Part II: therapeutic management and follow-up.
Circulation (2003); 108(6),772-778.
 ACUTE AORTIC SYNDROME:
Clinical suspicion and differential diagnosis 7.1
P.94

SYMPTOMS AND SIGNS DIFFERENTIAL DIAGNOSIS

SUGGESTIVE OF AAS

• Abrupt and severe chest/back pain with • Acute coronary syndrome

maximum intensity at onset (with/without ST-segment elevation)
• Pulse/pressure deficit • Aortic regurgitation without dissection
- Peripheral or visceral ischemia • Aortic aneurysms without dissection
- Neurological deficit • Musculoskeletal pain
• Widened mediastinum on chest X -ray • Pericarditis
• Risk factors for dissection • Pleuritis
• Other • Mediastinal tumours
- Acute aortic regurgitation • Pulmonary embolism
- Pericardial effusion • Cholecystitis
- Hemomediastinum/hemothorax • Atherosclerosis or cholesterol embolism
 General approach to the patient
with suspected ACUTE AORTIC SYNDROME 7.1
P.95
Consider acute aortic dissection in all patients presenting with:

• Chest, back or abdominal pain

• Syncope
• Symptoms consistent with perfusion deficit
(central nervous system, visceral myocardial or limb ischemia)

Pre-test risk assessment for acute aortic dissection

High-risk conditions High-risk pain features High-risk exam features

• Marfan’s syndrome Chest, back or abdominal pain • Perfusion deficit:

• Connective tissue disease described as: - Pulse deficit
• Family history of aortic disease - SBP differential
• Aortic valve disease Abrupt at onset, severe in intensity, - Focal neurological deficit
• Thoracic aortic aneurysm and ripping/sharp or stabbing quality • Aortic regurgitation murmur
• Hypotension or shock

Copyright: Hiratzka et al. 2010 Guidelines on Thoracic Aortic Disease. Circulation. (2010) ; 121: page-310 (fig 25 step 2).
 Laboratory tests required for patients
with ACUTE AORTIC dissection 7.1
P.96
Laboratory tests To detect signs of:
Red blood cell count Blood loss, bleeding, anaemia
White blood cell count Infection, inflammation (SIRS)
C-reactive protein Inflammatory response
ProCalcitonin Differential diagnosis between SIRS and sepsis
Creatine kinase Reperfusion injury, rhabdomyolysis
TroponinIorT Myocardial ischaemia, myocardial infarction
D-dimer Aortic dissection, pulmonary embolism, thrombosis
Creatinine Renal failure (existing or developing)
Aspartate transaminase / alanine aminotransferase Liver ischaemia, liver disease
Lactate Bowel ischaemia, metabolic disorder
Glucose Diabetes mellitus
Blood gases Metabolic disorder, oxygenation

Reference: Eur Heart J 2014; eurheartj.ehu281.

 ACUTE
ACUTECHEST PAIN
CHEST PAIN 7.1
P.97
Medical history + clinical examination + ECG STEMI a : see ESC guidelines 169

UNSTABLE HAEMODYNAMIC STATE STABLE

TTE + TOE/CT° Low probability (score 0-1) High probability (score 2-3)
or typical chest pain

AAS AAS D-dimers d,e + TTE + Chest X-ray TTE

confirmed excluded
Consider
alternate Definite Inconclusive
diagnosis Type A -ADc
No argument Signs Widened
for AD of AD media-
a
STEMI can be associated with AAS in rare cases. stinum
b
 ending local availability, patient
P Refer on emergency CT (or TOE)
Consider to surgical team and
characteristics, and physician experience. alternate pre-operative TOE
diagnosis
c
 roof of type-A AD by the presence of flap, aortic
P
regurgitation, and/or pericardial effusion. CT (MRI or TOE) b AAS Consider
d
Preferably point-of-care, otherwise classical. confirmed alternate
diagnosis
e
 lso troponin to detect non–ST-segment
A AAS Consider repeat CT
confirmed alternate if necessary
elevation myocardial infarction.
diagnosis

Flowchart for decision-making based on pre-test sensitivity of acute aortic syndrome. Reference: Eur Heart J 2014; eurheartj.ehu281.
 Details required from imaging in ACUTE AORTIC dissection 7.1
P.98

Aortic dissection • Visualization of intimal flap

• Extent of the disease according to the aortic anatomic segmentation
• Identification of the false and true lumens (if present)
• Localization of entry and re-entry tears (if present)
• Identification of antegrade and/or retrograde aortic dissection
• Identification grading, and mechanism of aortic valve regurgitation
• Involvement of side branches
• Detection of malperfusion (low flow or no flow)
• Detection of organ ischaemia (brain, myocardium, bowels, kidneys, etc.)
• Detection of pericardial effusion and its severity
• Detection and extent of pleural effusion
• Detection of peri-aortic bleeding
• Signs of mediastinal bleeding
Intramural • Localization and extent of aortic wall thickening
haematoma • Co-existence of atheromatous disease (calcium shift)
• Presence of small intimal tears
Penetrating aortic • Localization of the lesion (length and depth)
ulcer • Co-existence of intramural haematoma
• Involvement of the peri-aortic tissue and bleeding
• Thickness of the residual wall
In all cases • Co-existence of other aortic lesions: aneurysms, plaques, signs of inflammatory disease, etc.
ACUTE AORTIC SYNDROMES MANAGEMENT: General approach 7.1
ACUTE AORTIC SYNDROMES MANAGEMENT: GENERAL APPROACH
P.99
ACUTE AORTIC DISSECTION

Type A Type B
(Ascending aorta (No ascending
involvement) aorta involvement)

Complicated
Uncomplicated (malperfusion,
rupture)

Open Surgery Medical Endovascular

with/without treatment Therapy or
Endovascular Open Surgery
Therapy (TEVAR)
 ACUTE AORTIC SYNDROMES: Initial management 7.1
P.100

1 • Detailed medical history and complete physical examination (when possible)

2 • Standard 12-lead ECG: Rule-out ACS, documentation of myocardial ischemia

3 • Intravenous line, blood sample (CK, cTn, myoglobin, white blood count, D-dimer, hematocrit, LDH)

4 • Monitoring: HR and BP

5 • Pain relief (morphine sulphate) (see chapter 4)

6 • Noninvasive imaging (see previous page)

7 • Transfer to ICU

For more information on individual drug doses and indications,

SEE CHAPTER 9 DRUGS USED IN ACUTE CARDIOVASCULAR CARE
 ACUTE AORTIC SYNDROMES: Surgical management 7.1
ACUTE AORTIC SYNDROMES: SURGICAL MANAGEMENT
P.101
TYPE A ACUTE AORTIC DISSECTION TYPE B ACUTE AORTIC DISSECTION

URGENT SURGERY (<24h) Definitive diagnosis

Graft replacement of ascending aorta +/- arch by clinical presentation and imaging
with/without aortic valve or aortic root
replacement/repair (depending on aortic regurgitation Yes No
and aortic root involvement)
COMPLICATED UNCOMPLICATED
defined as: defined as:
• Impending rupture No features
• Malperfusion of complicated
Emergency Surgery Elective/individualised • Refractory HTN dissection
• Haemodynamic instability Surgery • SBP (<90 mmHg)
(hypotension/shock) • Non-complicated • Shock
• Tamponade intramural hematoma MEDICAL
• Severe acute aortic • Comorbidities MANAGEMENT
regurgitation • Age >80 years and imaging
MEDICAL MEDICAL
• Impending rupture surveillance protocol
MANAGEMENT MANAGEMENT
• Flap in aortic root
and and • On admission
• Malperfusion syndrome
TEVAR OPEN SURGERY • At 7 days
REPAIR • At discharge
if TEVAR • Every 6 months
contraindicated thereafter
 Risk-adjusted management strategies
in ACUTE PULMONARY EMBOLISM 7.2
P.102
Clinical suspicion
Yes No
Shock / hypotension?

Diagnostic Diagnostic algorithm as for suspected not high-risk PE

algorithm
as for suspected PE confirmed
high-risk PE

Assess clinical risk (PESI or SPESI)

PE confirmed
PESI Class III-IV PESI Class I-II
or sPESI ≥ I or sPESI = 0
Intermediate risk

Consider further
risk stratificaiton

RV function (echo or CT) a

Laboratory testing b

Both positive One positive

or both negative
 7.2
High-risk Intermediate-high risk Intermediate-low risk Low riskc
P.103

Primary A/C; monitoring Consider early

reperfusion consider rescue Hospitalization A/C e discharge and home
reperfusiond treatment if feasible f

a
If echocardiography has already been performed during diagnostic work-up for PE and detected RV dysfunction,
or if the CT already performed for diagnostic work–up has shown RV enlargement (RV/LV (left ventricular)
ratio ≥0.9, a cardiac troponin test should be performed except for cases in which primary reperfusion is
not a therapeutic option (e.g. due to severe comorbidity or limited life expectancy of the patient).
b
 arkers of myocardial injury (e.g. elevated cardiac troponin I or T concentrations in plasma), or of heart failure as a
M
result of (right) ventricular dysfunction (elevated natriuretic peptide concentrations in plasma). If a laboratory test for
a cardiac biomarker has already been performed during initial diagnostic work-up (e.g. in the chest pain unit) and was
positive, then an echocardiogram should be considered to assess RV function, or RV size should be (re)assessed on CT.
c
 atients in the PESI Class I-II, or with sPESI of 0, and elevated cardiac biomarkers or signs of RV dysfunction on imaging tests, are
P
also to be classified into the intermediate-low risk category. This might apply to situations in which imaging or biomarker results
become available before calculation of the clinical severity index. These patients are probably no candidates for home treatment.
d
 hrombolysis, if (and as soon as) clinical signs of haemodynamic decompensation appear; surgical
T
pulmonary embolectomy or percutaneous catheter-directed treatment may be considered as
alternative options to systemic thrombolysis, particularly if the bleeding risk is high.
e
 onitoring should be considered for patients with confirmed PE and a positive troponin test,
M
even if there is no evidence of RV dysfunction on echocardiography or CT.
f
 he simplified version of the PESI has not been validated in prospective home treatment trials; inclusion
T
criteria other than the PESI were used in two single-armed (non-randomized) management studies.
Reference: Eur Heart J 2014; 35:3033-3073.
 ACUTE PULMONARY EMBOLISM: DIAGNOSIS
ACUTE PULMONARY EMBOLISM: Diagnosis 7.2
P.104
CARDIOVASCULAR RESPIRATORY
Symptoms/Signs Symptoms/Signs
including but not limited to: Dyspnea including but not limited to:

• Chest pain (angina) Suspect • Chest pain (pleural)

• Syncope • Pleural effusion
• Tachycardia
acute • Tachypnea
• ECG changes PE • Hemoptysis
• NT-proBNP ↑ • Hypoxemia
• Troponin ↑ • Atelectasis

YES
Shock? or NO
SBP <90 mmHg?
or
SBP fall by >40 mmHg?
persisting >15 min, otherwise unexplained

Management algorithm Management algorithm

for UNSTABLE patients for initially STABLE patients
Reference: IACC Textbook (2015) chapter 66 Pulmonary embolism - page 638 - figure 66.1.
 MANAGEMENT ALGORITHM FOR UNSTABLE PATIENTS WITH
Management
SUSPECTEDalgorithm for unstable
ACUTE PULMONARY patients
EMBOLISM
with suspected ACUTE PULMONARY EMBOLISM 7.2

CT angiography immediately available

P.105
No and patient stabilised Yes

Echocardiography CT*
(bedside) Angio
patient stabilised
RV pressure overload
Right heart,
Yes CUS pulmonary artery or
venous thrombi?
TEE
No
Yes positive

No further diagnostic
tests feasible
Search for other causes
Primary PA reperfusion
Primary PA reperfusion not justified
negative
* Consider also pulmonary angiography if unstable patient in hemodynamic lab.

Reference: IACC Textbook (2015) chapter 66 Pulmonary embolism - page 639 - figure 66.2.
 ACUTE PE: Management strategy for initially unstable patients
with confirmed high risk pulmonary embolism 7.2
P.106

Shock or hypotension YES

Contraindications
No Relative Absolute
for thrombolysis

Low-­dose Surgical or
Primary PA
transcatheter Percutaneous catheter
reperfusion Thrombolysis
thrombolysis / embolectomy
strategy
clot fragmetation (availability/experience)

Supportive treatment i.v. UFH, STABILISE SYSTEMIC BLOOD PRESSURE, CORRECT HYPOXEMIA
 Management algorithm for initially stable patients
MANAGEMENT ALGORITHM
with suspected FOR INITIALLY
ACUTE PULMONARYSTABLE PATIENTS WITH
EMBOLISM 7.2
SUSPECTED ACUTE PULMONARY EMBOLISM
P.107
Asses clinical (pre-test) probalility

Low or intermediate High or

“PE unlikely“ “PE likely“

negative D-dimer

positive CUS

CT angiography CT angiography CUS

positive

negative
negative positive Confirm by CUS positive
V/Q scan or angiography

Anticoagulation Anticoagulation Anticoagulation Anticoagulation

not justified required not justified required

Reference: IACC Textbook (2015) chapter 66 Pulmonary embolism - page 640 - figure 66.3.
 Suggested management strategy for initially stable patients
with (non-high risk) confirmed PE 7.2
P.108

Markers for myocardial injury Positive Positive Negative

Markers for RV overload Positive Positive Negative

Clinical risk assessment

Positive (class III-V) Positive (class III-V) Negative (class I-II)
score (PESI)

Suggested initial LMWH/Fonda/apixaban/

UFH i.v./LMWH s.c. apixaban/rivaroxaban
anticoagulation rivaroxaban

Monitoring (ICU)* Hospitalisation** Early

STRATEGY
rescue thrombolysis (telemonitoring) discharge***

* When all markers are positive. - ** When at least one marker is positive. - *** When all markers are negative.

For more information on individual drug doses and indications,

SEE CHAPTER 9 DRUGS USED IN ACUTE CARDIOVASCULAR CARE
 PULMONARY EMBOLISM: Pharmacological treatment 7.2
Key drugs for initial treatment of patients with confirmed PE P.109

Alteplase (rtPA) (intravenous) 100 mp/2h

or 0.6 mp/kg/15 min (max 50 mp)
Unstable

Urokinase (intravenous) 3 million IU over 2h

Streptokinase (intravenous) 1.5 million IU over 2h
Unfractionated heparin (intravenous) 80 IU/kg bolus + 18 IU/kg/h
Enoxaparine (subcutaneous) 1 mp/kg BID or 1.5 mp/kg QD
Tinzaparin (subcutaneous) 175 U/kg QD
Fondaparinux (subcutaneous) 7.5 mp (50-100 kg of body weight)
Stable

5 mp for patients <50 kg,

10 mp for patients >100 kg
Rivaroxaban (oral) 15 mp BID
(for 3 weeks, then 20 mp QD)
Apixaban (oral) 10 mg bid (for 7 days, than 5 mg bid)

For more information on individual drug doses and indications,

SEE CHAPTER 9 DRUGS USED IN ACUTE CARDIOVASCULAR CARE
 8

CHAPTER 8
ACUTE MYOCARDIAL/
PERICARDIAL SYNDROMES
8.1 ACUTE MYOCARDITIS ����������������������������������������������������� p.112
A. Keren, A. Caforio

8.2 ACUTE PERICARDITIS AND CARDIAC TAMPONADE ���������������������� p.117

C. Vrints, S. Price
 ACUTE MYOCARDITIS: Definition and causes 8.1
P.112
MYOCARDITIS (WHO /ISFC): Inflammatory disease of the myocardium diagnosed
by established histological, immunological and immunohistochemical criteria.

CAUSES OF MYOCARDITIS

INFECTIOUS IMMUNE-MEDIATED TOXIC

• Viral • Allergens: Tetanus toxoid, vaccines, • Drugs
• Bacterial serum sickness, Drugs • Heavy Metals
• Spirochaetal • Alloantigens: Heart transplant rejection • Hormones, e.g.
• Fungal • Autoantigens: Infection-negative lymphocytic, catecholamines
• Protozoal infection-negative giant cell, (Pheochromocytoma)
• Parasitic associated with autoimmune or • Physical agents
• Rickettsial immune oriented disorders
 ACUTE MYOCARDITIS: Diagnostic criteria (1)
Diagnostic criteria for clinically suspected myocarditis
Clinical presentations
with or without ancillary findings
• Acute chest pain (pericarditic or pseudo-ischemic)
• New-onset (days up to 3 months) or worsening
dyspnea or fatigue, with or without left/right heart
failure signs
• Palpitation, unexplained arrhythmia symptoms,
syncope, aborted sudden cardiac death
• Unexplained cardiogenic shock
and/or pulmonary oedema
Ancillary findings which support
the clinical suspicion of myocarditis
• Fever ≥38.1°C within the preceding 30 days
• A respiratory or gastrointestinal infection
• Previous clinically suspected or biopsy proven
myocarditis
• Peri-partum period
• Personal and/or family history of allergic asthma
• Other types of allergy
• Extra-cardiac autoimmune disease
• Toxic agents
• Family history of dilated cardiomyopathy, myocarditis
Reference: Caforio ALP et al. Eur Heart J. (2013) Jul 3 (15).
8.1
P.113
Diagnostic criteria
I. ECG/Holter/stress test features: Newly abnormal ECG and/or Holter
and/or stress testing, any of the following: 
• I to III degree atrioventricular block, or bundle branch block,
ST/T wave changes (ST elevation or non ST elevation, T wave inversion),
• Sinus arrest, ventricular tachycardia or fibrillation and asystole,
atrial fibrillation, frequent premature beats, supraventricular tachycardia
• Reduced R wave height, intraventricular conduction delay
(widened QRS complex), abnormal Q waves, low voltage
II. Myocardiocytolysis markers: Elevated cTnT/cTnI
III. Functional/structural abnormalities on echocardiography
• New, otherwise unexplained LV and/or RV structure and function
abnormality (including incidental finding in apparently asymptomatic
subjects): regional wall motion or global systolic or diastolic function
abnormality, with or without ventricular dilatation, with or without
increased wall thickness, with or without pericardial effusion, with
or without endocavitary thrombi
IV. Tissue characterisation by CMR:
Edema and/or LGE of classical myocarditic pattern
 ACUTE MYOCARDITIS: Diagnostic criteria (2)
Acute myocarditis should be clinically suspected in the presence of: 8.1
P.114
One or more of the clinical presentations shown in the Diagnostic Criteria* with or without Ancillary Features*
AND
One or more Diagnostic Criteria from different categories (I to IV)*

OR

when the patient is asymptomatic, two or more diagnostic criteria from different categories (I to IV)*

in the absence of:

1) angiographically detectable coronary artery disease

2) known pre-existing cardiovascular disease or extra-cardiac causes that could explain the syndrome
(e.g. valve disease, congenital heart disease, hyperthyroidism, etc.)

Suspicion is higher with higher number of fulfilled criteria*

Endomyocardial biopsy is necessary to:

1) confirm the diagnosis of clinically suspected myocarditis,
2) identify the type and aetiology of inflammation,
and 3) provide the basis for safe immunosuppression
(in virus negative cases).

*SEE CHAPTER 9 DRUGS USED IN ACUTE CARDIOVASCULAR CARE

Reference: Caforio ALP et al. Eur Heart J. (2013) Jul 3 (16).

 ACUTE MYOCARDITIS: Diagnostic and management protocol 8.1
History, Physycal examination; ECG; Echocardiogram; Laboratory tests P.115
(Troponin, CRP, ESR, blood cell count, BNP); CMR; If available, serum cardiac autoantibodies

Clinically suspected myocarditis

Consider coronary angiography and EMB

No coronary artery disease

Hemodynamically stable Hemodynamically unstable,

Preserved LV function decreased LV function, cardiogenic shock
No eosinophilia
No significant rhythm or
conduction disturbances Pharmacological and, if needed,
Not associated with mechanical circulatory support (ECMO, LVAD/Bi-VAD,
systemic immune disease* bridge to heart transplant or to recovery)

Lymphocytic Giant cell, eosinophilic,

sarcoidosis (acute decompensation)
General supportive therapy
General supportive therapy
Immunosuppression if Immunosuppression
unresponsive and virus negative EMB if infection-negative EMB
*If myocarditis is associated with systemic immune disease exacerbation, therapy overlaps with treatment of the background disease (usually immunosuppression).
 Management of patients
with life-threatening ACUTE MYOCARDITIS 8.1
P.116

• Patients with a life-threatening presentation should be sent to specialised units with capability for
hemodynamic monitoring, cardiac catheterisation and expertise in endomyocardial biopsy.

• In patients with hemodynamic instability a mechanical cardio-pulmonary assist device

may be needed as a bridge to recovery or to heart transplantation.

• Heart transplant should be deferred in the acute phase, because recovery may occur, but can be considered
for hemodynamically unstable myocarditis patients, including those with giant cell myocarditis, if optimal
pharmacological support and mechanical assistance cannot stabilise the patient

• ICD implantation for complex arrhythmias should be deferred until resolution of the acute episode, with
possible use of a lifevest during the recovery period.

Reference: Caforio ALP et al. Eur Heart J. 2013 Jul 3 (18).

 ACUTE PERICARDITIS: Diagnosis 8.2
P.117
DIAGNOSIS (≥ 2 of the following):
• Chest pain (pleuritic) varying with position
• Pericardial friction rub
• Typical ECG changes (PR depression and/or diffuse concave ST-segment elevation)
• Echocardiography: new pericardial effusion

Yes Equivocal or no

Consider Consider
cardiac alternative
MRI diagnoses

Myopericarditis if: Acute Delayed

↑ Troponin enhancement
pericarditis
Echocardiography: ↓ LV-function pericardium
 ACUTE
ACUTEPERICARDITIS: Management
PERICARDITIS: MANAGEMENT 8.2
P.118
Acute pericarditis

Most frequent cause:

Other causes High-risk features? Viral pericarditis
• Post cardiac injury syndrome • Fever >38°C
• Post cardiac surgery • Subacute onset
• Post MI: Dressler syndrome • Anticoagulated
• Uremic • Trauma
• Neoplastic • Immunocompromised No
• Collagen vascular diseases (e.g. SLE) • Hypotension
• Bacterial • Jugular venous distension
• Tuberculous • Large effusion Outpatient treatment

Yes Aspirin 800 mg

or Ibuprofen 600 mg BID - 2 weeks

Stable Hospital admission

If persisting or recurrent chest pain :
Add colchicine 0.5 mg once (<70 kg)
Ibuprofen + colchicine Tamponade? or 0.5 mg BID (≥70 kg) for 3 months
Further testing for underlying etiology Avoid corticosteroids!
Pericardiocentesis
 CARDIAC TAMPONADE: Diagnosis and management 8.2
CARDIAC TAMPONADE: DIAGNOSIS AND MANAGEMENT
P.119
Physical examination Tamponade ? Not performed in routine
• Distended neck veins Cardiac catheterization
• Shock Early
• Pulsus paradoxus Echocardiography • Right atrial pressure ↑
• Muffled heart sounds with respirometer • Loss of X-descent
ECG Late
• Sinus tachycardia • Aortic pressure ↓
• Microvoltage QRS • Presence of a moderate to large • Pulsus paradoxus
• Electrical alternans pericardial effusion • Intracardiac diastolic
• Diastolic collapses of right atrium and pressure equilibration
right ventricle
• Ventricular interdependence
• Increased tricuspid and pulmonary flow
velocities (>50%) with decreased mitral
and aortic flow velocities (>25%) during
inspiration (predictive value >90%)

Percutaneous
pericardiocentesis & drainage
Consider surgical drainage
Avoid PEEP ventilation Tamponade
 9
P.121

CHAPTER 9
DRUGS IN
ACUTE CARDIOVASCULAR
CARE
Ana de Lorenzo
 Oral antiplatelets 9
P.122
Dose
Drug Indications Dose Comments
adjustments
Primary (not universally approved) LD (if ACS): Major contraindications:
Aspirin

and secondary cardiovascular 150-300 mg oral GI bleeding-active peptic ulcer

-
disease prevention MD: 75-100 mg
oral QD
ACS (all patients at moderate-to-high LD: 180 mg oral Major contraindications: previous intracerebral
Ticagrelor

risk of ischaemic events, e.g. elevated MD: 90 mg oral BID - hemorrhage, severe hepatic impairment,
cardiac troponins) strong CYP3A4 inhibitors
Secondary prevention MD: 60 mg oral BID
1-3 years post-MI -

ACS with planned PCI LD: 60 mg oral MD: 5 mg QD Contraindication:
Prasugrel

MD: 10 mg oral QD weight <60kg previous stroke/TIA

Prasugrel is generally not recommended in
elderly, and if positive benefit/risk 5 mg is
recommended

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Oral antiplatelets (Cont.) 9
P.123
Dose
Drug Indications Dose Comments
adjustments
ACS + PCI or medical management LD: 300-600 mg Prasugrel and ticagrelor have not been studied
(patients who cannot receive oral as adjuncts to fibrinolysis and oral anticoagulants
ticagrelor or prasugrel) and in MD: 75 mg oral QD
-
ACS patients at high bleeding risk
(e.g. patients who require oral
Clopidogrel

anticoagulation)
STEMI LD: 300 mg oral
-
+ fibrinolysis <75 years MD: 75 mg oral QD
STEMI LD: 75 mg oral Prasugrel and ticagrelor have not been studied
-
+ fibrinolysis ≥75 years MD: 75 mg oral QD as adjuncts to fibrinolysis and oral anticoagulants
Secondary prevention >12 months MD: 75 mg oral QD
-
post coronary stenting

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Intravenous antiplatelets 9
P.124
Dose
Drug Indications Dose Comments
adjustments
Adjunct to PCI for bailout LD: 0.25 mg/Kg i.v. Contraindications:
situations or thrombotic MD: 0.125 μg/Kg/ Active internal bleeding - History of CVA within 2 years
complications min i.v. (max: 10 μg/ - Bleeding diathesis - Preexisting thrombocytopenia
Abciximab

min) for 12h - Recent (within 2 months) intracranial or intraspinal

- surgery or trauma - Recent (within 2 months) major
surgery - Intracranial neoplasm, arteriovenous
malformation, or aneurysm - Severe uncontrolled
hypertension - Presumed or documented history of
vasculitis - Severe hepatic failure or severe renal failure
requiring haemodialysis - Hypertensive retinopathy
ACS treated medically LD: 180 μg/Kg i.v. Reduce infusion Contraindications:
or with PCI (at a 10 min dose to 1 μg/kg/ Bleeding diathesis or bleeding within the previous
interval) min if CrCl  30 days - Severe uncontrolled hypertension - Major
Eptifibatide

If STEMI and PCI: 30-50 ml/min surgery within the preceding 6 weeks - Stroke within
add a second 30 days or any history of hemorrhagic stroke -
180 mcg/kg i.v. Coadministration of another parenteral GP II b/III a
bolus inhibitor - Severe renal impairment or dependency on
at 10 min renal dialysis - History of intracranial disease - Clinically
MD: 2 μg/Kg/min i.v. significant hepatic impairment - Thrombocytopenia -
infusion Prothrombine time >1.2 times control or INR ≥2

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Intravenous antiplatelets (Cont.) 9
P.125
Dose
Drug Indications Dose Comments
adjustments
ACS treated medically LD: 25 μg/Kg i.v. CrCl <30 ml/min: Contraindications:
or with PCI over 5 min decrease 50%
Tirofiban

MD: 0.15 μg/Kg/ bolus and infusion A history of thrombocytopenia following prior exposure

All patients undergoing PCI
(elective + ACS)
Cangrelor
min i.v. Infusion to dose
Active internal bleeding or a history of bleeding
18 hours
diathesis, major surgical procedure or severe physical
trauma within the previous month
IV Bolus Major contraindications:
of 30 μg/Kg

immediate onset + rapid + Significant active bleeding or stroke

offset
(platelet recovery in 60min)
IV infusion -
Transition to oral P2Y12 inhibitors variable
of 4 μg/kg/min
according to type of agent
for at least 2 hours
from start of PCI

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Oral anticoagulants and antagonists 9
P.126
Drug Indications Dose Dose adjustments Comments
Treatment and INR goal of 2-3 Assessing individual risks for
Acenocoumarol

prophylaxis (INR: 2.5-3.5 for mechanical thromboembolism and bleeding

Warfarin

of thrombosis mitral valve prostheses or

double valve replacement) -

Prevention of stroke 5 mg oral BID 2.5 mg oral BID

and systemic embolism 1) when at least 2 of the following
in NVAF characteristics: age ≥80,
Cr >1.5 mg/dl or weight <60Kg
2) when CrCl 15-29 ml/min
Apixaban

Contraindicated if CrCl <15 ml/min
Treatment of DVT and PE 10 mg oral BID for the first or severe hepatic impairment
7 days -
followed by 5 mg oral BID

Prevention of recurrent 2.5 mg oral BID

DVT and PE -

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Oral anticoagulants and antagonists (Cont.) 9
P.127
Drug Indications Dose Dose adjustments Comments
Prevention of stroke 150 mg oral BID 110 mg BID Contraindicated if CrCl <30 ml/min
and systemic embolism (if age ≥80, increased bleeding or severe hepatic impairment
in NVAF risk or concomitant use of Active clinically significant bleeding
verapamil)
Dabigatran

Treatment of DVT and PE Concomitant treatment

in patients who have been with systemic ketoconazole,
treated with a parenteral cyclosporine, itraconazole and
anticoagulant for 5-10 dronedarone
days and prevention of
recurrent DVT and PE in
patients who have been
previously treated
Prevention of stroke and 60 mg oral QD 30 mg oral QD Edoxaban can be initiated
systemic embolism in 1) when CrCl 15-50 ml/min in patients who may require
Edoxaban

NVAF 2) weight <60Kg cardioversion. Treatment should

3) concomitant use of the be started at least 2 hours before
Treatment of DVT and 60 mg oral QD following P-glycoprotein inhibitors: cardioversion
PE and prevention of ciclosporin, dronedarone,
recurrent DVT and PE erythromycin, or ketoconazole.

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Oral anticoagulants and antagonists (Cont.) 9
P.128
Drug Indications Dose Dose adjustments Comments
Prevention of stroke and 20 mg oral QD CrCl <50 ml/min: 15 mg QD Contraindicated if CrCl <15 ml/min
systemic embolism in or hepatic disease associated with
NVAF coagulopathy and clinically relevant
Rivaroxaban

bleeding risk
Treatment of DVT and 15 mg oral BID for the first Reduce the maintenance dose to
PE and prevention of 3 weeks 15 mg QD if bleeding risk outweighs Rivaroxaban can be initiated
recurrent DVT and PE followed by 20 mg QD the risk for recurrent DVT and PE in patients who may require
(not formally approved) cardioversion

Prevention of 2.5 mg oral BID Treatment should be started at

- least 4 hours before cardioversion
atherothrombotic events

Anticoagulant antagonists
Specific reversal agent 5g i.v. over 5 to 10 min Dabigatran treatment can be re-
for dabigatran Another 5g dose if prolonged initiated 24h after administration of
Idarucizumab

clotting times and: idarucizumab, other antithrombotic

- recurrence of clinically therapy at any time
relevant bleeding - Relevant coagulation parameters
- if potential re-bleeding are aPTT, dTT or ECT
would be life-threatening
- second emergency
surgery/urgent procedure

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Oral anticoagulants and antagonists (Cont.) 9
P.129
Drug Indications Dose Dose adjustments Comments
Anticoagulant antagonists
Patients with asymptomatic high INR with or without mild haemorrhage

Anticoagulant INR Oral Vitamin K i.v. Vitamin K

5-9 1-2.5 mg or 2-5 mg for a rapid reversal 0.5-1 mg
(additional dose of 1-2 mg if INR
Phytomenadione (Vitamin K)

Warfarin remains high after 24h)

>9 2.5-5 mg (up to 10 mg) 1 mg
5-8 1-2 mg 1-2 mg
Acenocoumarol
Reversal for vitamin K >8 3-5 mg 1-2 mg
antagonists
Severe or life-threatening haemorrhage
Anticoagulant Situation i.v. Vitamin K Concomitant treatment
Severe 5-10 mg CCP or FFP
Warfarin haemorrhage
Life-threatening 10 mg CCP, FFP or rFVIIa
Severe 5 mg CCP, FFP or rFVIIa
Acenocoumarol
haemorrhage
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Parenteral anticoagulants 9
P.130
Drug Indications Dose Dose adjustments Comments
NSTE-ACS LD: 4,000 IU i.v. MD: 1,000 IU/h i.v. Target aPTT: 50-70s or 1.5 to Monitoring for heparin-induced
2.0 times that of control to be thrombocytopenia (HIT)
monitored at 3, 6, 12 and 24h Dose-independent reaction
STEMI Primary PCI: 70-100 IU/Kg i.v. when no Target aPTT: 50-70s or 1.5 to
GP-IIb/IIIa inhibitor is planned. 50-60 IU/Kg i.v. 2.0 times that of control to be
UFH

bolus with GP-IIb/IIIa inhibitors - Fibrinolysis/ monitored at 3, 6, 12 and 24h

No reperfusion: 60 IU/kg i.v. bolus (max:
4,000 IU) followed by an i.v. infusion of 12 IU/kg
(max: 1,000 IU/h) for 24-48h
Treatment of DVT 80 IU/Kg i.v. bolus According to aPTT,
and PE followed by 18 IU/Kg/h thromboembolic and bleeding risk
NSTE-ACS 2.5 mg QD s.c. up to 8 days or hospital discharge - Acute bacterial endocarditis
Severe hepatic impairment:
Fondaparinux

STEMI Fibrinolysis/No reperfusion: 2.5 mg i.v. bolus

caution advised
followed by 2.5 mg QD s.c. up to 8 days -
or hospital discharge Contraindicated
if CrCl <20 ml/min
Treatment of 5 mg QD s.c. (<50kg); 7.5 mg QD s.c. If >100Kg and CrCl 30-50 ml/min: Contraindicated for DVT/PE
DVT and PE (50-100kg); 10 mg QD s.c. (>100kg) 10 mg followed by 7.5 mg/24h s.c. treatment if CrCl <30 ml/min
Prevention of VTE 2.5 mg QD s.c. CrCl 20-50 ml/min: 1.5 mg QD s.c.

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Parenteral anticoagulants (Cont.) 9
P.131
Drug Indications Dose Dose adjustments Comments
PCI for NSTE-ACS 0.75 mg/kg i.v. bolus followed immediatelly Patients undergoing PCI Contraindicated
by 1.75 mg/kg/h infusion which may be with CrCl 30-50 ml/min should if CrCl <30 ml/min
continued for up to 4h post PCI as clinically receive a lower infusion rate of
warranted and further continued at a reduced 1.4 mg/kg/h Active bleeding or increased
infusion dose of 0.25 mg/kg/h for 4-12h as risk of bleeding, severe
No change for the bolus dose
clinically necessary uncontrolled hypertension,
subacute bacterial endocarditis
Bivalirudin

PCI for STEMI 0.75 mg/kg i.v. bolus followed immediatelly

by 1.75 mg/kg/h infusion which should be
continued for up to 4h after the procedure
After cessation of the 1.75 mg/kg/h infusion,
a reduced infusion dose of 0.25 mg/kg/h may
be continued for 4-12h
PCI for elective 0.75 mg/kg i.v. bolus followed immediatelly
cases by 1.75 mg/kg/h infusion which may be
continued for up to 4h post PCI
as clinically waranted

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Parenteral anticoagulants (Cont.) 9
P.132
Drug Indications Dose Dose adjustments Comments
NSTE-ACS 30 mg i.v. + 1 mg/kg s.c. BID If >75 years: no LD and MD Monitoring for HIT
0.75 mg/Kg BID s.c. Anti Xa monitoring during
CrCl <30 ml/min: no LD and MD treatment with LMWH might
1 mg/Kg QD s.c. be helpful in pregnancy,
If >75 years and CrCl <30 ml/min: extreme body weights and renal
no LD and 0.75 mg/Kg QD s.c. impairment
STE-ACS Primary PCI: 0.5 mg/Kg i.v. bolus In patients with CrCl <30 ml/min:
Fibrinolysis/No reperfusion: regardless of age, the s.c. doses
Enoxaparin

a) Age <75 years: 30 mg i.v. bolus followed by are given once daily
1 mg/Kg BID s.c. until hospital discharge for a
max of 8 days
The first two doses should not exceed 100 mg
b) Age >75 years: no bolus; 0.75 mg/Kg
BID s.c. - The first two doses should not
exceed 75 mg
Treatment of DVT 1 mg/Kg s.c. BID or 1.5 mg/Kg s.c. QD CrCl <30 ml/min: 1 mg/Kg/24h
and PE s.c.
Prevention of VTE 40 mg s.c. QD CrCl <30 ml/min: 20 mg s.c. QD

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Parenteral anticoagulants (Cont.) 9
P.133
Drug Indications Dose Dose adjustments Comments
Prevention of VTE 3,500 IU s.c. QD (moderate risk) Monitoring for HIT
Tinzaparin

-
4,500 IU s.c. QD (high risk) Anti Xa monitoring during
Treatment of DVT 175 IU/Kg s.c. QD treatment with LMWH might
- be helpful in pregnancy,
and PE
extreme body weights and renal
Prevention of VTE 2,500 IU s.c. QD (moderate risk) impairment
-
5,000 IU s.c. QD (high risk) Dalteparin:
Treatment of DVT 200 IU/Kg QD or 100 IU/Kg BID s.c. Anti Xa monitoring In cancer patients, dose of
Dalteparin

and PE if renal impairment 200 IU/kg (max: 18,000 IU)/24h

for 1 month, followed by 150 IU/
kg/24h for 5 months
After this period, vitamin K antag
or a LMWH should be continued
indefinitely or until the cancer is
considered cured
Anticoagulant in Initial i.v. infusion dose: 2 μg/kg/min Renal and hepatic impairment: Monitored using aPTT goal:
Argatroban

patients with HIT (not to exceed 10 μg/kg/min) caution advised 1.5 to 3.0 times the initial
Patients undergoing PCI: 350 μg/kg i.v. baseline value
followed by 25 μg/kg/min i.v.
PCI: ACT goal: 300-450s

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.

Drug Indications
STEMI <12 hours
Streptokinase (SK)
Treatment of PE
STEMI <12 hours
Alteplase (tPA)
Treatment of PE
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
Fibrinolytics
Dose
1.5 million units over 30-60 min
i.v.
250,000 IU as a LD over 30min,
followed by 100,000 IU/h over
12-24h
15 mg i.v. bolus:
0.75 mg/kg over 30 min
(up to 50 mg) then
0.5 mg/kg over 60 min i.v.
(up to 35 mg)
Total dose of 100 mg: 10 mg
i.v. bolus followed by 90 mg i.v.
for 2h
9
P.134
Dose
Comments
adjustments
Absolute contraindications to
- fibrinolytics:
Previous intracranial haemorrhage or
stroke of unknown origin at any time
Ischaemic stroke in the preceding 6
months
-
Central nervous system damage
or neoplasms or atrioventricular
malformation
Recent major trauma/surgery/head injury
(within the preceding 3 weeks)
- Gastrointestinal bleeding
within the past month
Known bleeding disorder (excluding
If weight <65 Kg: max menses)
dose <1.5 mg/kg Aortic dissection
Non-compressible punctures in the past
24h (e.g. liver biopsy, lumbar puncture)
 Fibrinolytics (Cont.) 9
P.135
Dose
Drug Indications Dose Comments
adjustments
STEMI <12 hours 10 units + 10 units i.v. bolus given Renal and hepatic Absolute contraindications to
30 min apart impairment: fibrinolytics:
Reteplase

caution advised
(rt-PA)

Previous intracranial haemorrhage or

stroke of unknown origin at any time
Ischaemic stroke in the preceding 6
months
Central nervous system damage
STEMI <12 hours Single i.v. bolus over 10 seconds: or neoplasms or atrioventricular
malformation
30 mg if <60kg
Recent major trauma/surgery/head injury
35 mg if 60 to <70kg
(within the preceding 3 weeks)
Tenecteplase

40 mg if 70 to <80kg
(TNK-tPA)

45 mg if 80 to <90kg Gastrointestinal bleeding

50 mg if ≥90kg - within the past month
Known bleeding disorder (excluding
menses)
Aortic dissection
Non-compressible punctures in the past
24h (e.g. liver biopsy, lumbar puncture)

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Antiischemic drugs 9
P.136
Drug Indications Dose Dose adjustments Comments
Beta-blockers: Preferred over calcium channel blockers - Contraindicated if coronary spasm, severe bradycardia, AV block, severe bronchospasm

NSTE-ACS LD: 25-100 mg oral Elderly: start at Only if normal LVEF

MD: 25-100 mg QD a lower dose
Atenolol

CrCl 15-35 ml/min:
STEMI 25-100 mg QD, max dose 50 mg/day;
titrate as tolerated up to 100 mg QD CrCl <15 ml/min:
only if no LVSD or CHF max dose 25 mg/day

NSTE-ACS LD: 3.125-25 mg oral Caution in elderly and hepatic Preferred if LVSD/HF
Carvedilol

MD: 3.125-25 mg BID impairment

STEMI 3.125-6.25 mg BID,

titrated as tolerated up to 50 mg BID

NSTE-ACS LD: 1.25-10 mg oral Caution in renal or hepatic impairment Preferred if LVSD/HF
Bisoprolol

MD: 1.25-10 mg QD

STEMI 1.25-5 mg QD,

titrate as tolerated up to 10 mg QD

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Antiischemic drugs (Cont.) 9
P.137
Drug Indications Dose Dose adjustments Comments
Beta-blockers: Preferred over calcium channel blockers - Contraindicated if coronary spasm, severe bradycardia, AV block, severe bronchospasm
NSTE-ACS LD: 25-100 mg oral Caution in hepatic impairment Preferred if LVSD/HF
Metoprolol

MD: 25-100 mg BID

STEMI 5-25 mg BID,

titrate as tolerated up to 200 mg QD
Calcium antagonists: Consider if beta-blockers are contraindicated. First option in vasospastic angina
ACS LD: 80-120 mg oral Caution in elderly, renal Contraindicated if
Verapamil

MD: 80-240 mg TID-QD or hepatic impairment bradycardia,

HF, LVSD

ACS LD: 60-120 mg oral Caution in elderly and hepatic Contraindicated if

Diltiazem

MD: 60-300 mg TID-QD impairment bradycardia,

HF, LVSD

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Antiischemic drugs (Cont.) 9
P.138
Drug Indications Dose Dose adjustments Comments
Calcium antagonists: Consider if beta-blockers are contraindicated. First option in vasospastic angina
ACS LD: 5-10 mg oral, MD: 5-10 mg QD Caution in hepatic impairment Contraindicated
Amlodipine

if hypotension

Nitrates
ACS If intolerant or unresponsive to Contraindicated
nitroglycerin s.l. 5 μg/min - Increase by if severe
5 mcg/min q 3-5 min up to 20 μg/min hypotension and co-
i.v.

-
If 20 mcg/min is inadequate, increase by administration with
10 to 20 μg/min every 3 to 5 min phosphodiesterase
Nitroglycerin

Max dose: 400 μg/min inhibitors

Angina 1-2 puff s.l. every 5 min as needed, The most common
spray

up to 3 puffs in 15 min - adverse effects

are headache and
dizziness
Angina 0.3 to 0.6 mg s.l. or in the buccal pouch
sublingual

i.v. nitroglycerin
tablet

every 5 min as needed, up to 3 doses

- requires NON-PVC
in 15 min
containers

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Antiischemic drugs (Cont.) 9
P.139
Drug Indications Dose Dose adjustments Comments
Angina 5-10 mg BID with the two doses given Contraindicated
Isosorbide mononitrate

7h apart (8am and 3pm) to decrease if severe

tolerance development - then titrate to hypotension and co-
10 mg BID in first 2-3 days administration with
Extended release tablet: Initial: 30- phosphodiesterase
-
60 mg given in the morning as a single inhibitors
dose The most common
Titrate upward as needed, giving at least adverse effects
3 days between increases are headache and
Max daily single dose: 240 mg dizziness
Angina Initial dose: 5 to 20 mg orally 2 or
Isosorbide
dinitrate

3 times/day
MD: 10 to 40 mg orally 2 or 3 times a day -
Extended release: 40 to 160 mg/day
orally

Angina 0.2 to 0.4 mg/h patch applied topically

Nitroglycerin
transdermal

once a day for 12 to 14h per day;

patch

titrate as needed and tolerated up

to 0.8 mg/h -

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Antiischemic drugs (Cont.) 9
P.140
Drug Indications Dose Dose adjustments Comments
Other antiishemic drugs
Stable angina 5-7.5 mg oral BID Caution in elderly and CrCl <15 ml/min Contraindicated
Ivabradine

if severe hepatic
impairment

Stable angina Initial dose: 375 mg oral BID Use with caution in renal and hepatic Contraindicated
After 2-4 weeks, the dose should be impairment, CHF, elderly, low weight if CrCl <30 ml/
Ranolazine

titrated to 500 mg BID and, according to min, concomitant

the patient’s response, further titrated to administration of
a recommended max dose of 750 mg BID potent CYP3A4
inhibitors, moderate
or severe hepatic
impairment
Stable angina Modified-release: 35 mg oral BID Caution in elderly Contraindicated in
and 30 <CrCl <60 ml/min parkinson disease,
Trimetazidine

parkinsonian
symptoms, tremors,
restlessleg syndrome,
movement disorders,
severe renal
impairment

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Lipid lowering drugs 9
P.141
Drug Indications Dose Dose adjustments Comments
Statins: Primary or secondary prevention of cardiovascular disease
For secondary prevention, start with high doses initiated early after admission and downtitrate if side effects.
Target LDL-C levels <70 mg/dl

Atorvastatin -
LDL-C reduction
CrCl <30 ml/min: start 5 mg QD,
Rosuvastatin <30% 30-40% 40-50% >50% max: 10 mg QD

Simva Simva Simva/ezet Simva/ezet CrCl 30-59 ml/min: start 1 mg

Pitavastatin 10 mg 20-40 mg 20/10 mg 40/10 mg QD, max 2 mg/day; Contraindicated
CrCl 10-29 ml/min: not defined in patients with
Lova Ator Ator Ator active liver disease
20 mg 10 mg 20-40 mg 40-80 mg Severe renal impairment: or with unexplained
Simvastatin start 5 mg QPM elevation of liver
Prava Rosu
Rosu 5 mg Rosu 10 mg Caution in severe renal function enzyme
Fluvastatin 10-40 mg 20-40 mg
impairment levels
Pita 1 mg Pita 2 mg Pita 4 mg
Significant renal impairment:
Pravastatin start 10 mg QD
Fluva
Fluva 80 mg
20-40 mg CrCl <30 ml/min:
Lovastatin caution if dose >20 mg QD

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Lipid lowering drugs (Cont.) 9
P.142
Drug Indications Dose Dose adjustments Comments
Others
Hypercholesterolaemia 10 mg oral QD Avoid use if moderate-severe
Ezetimibe hepatic impairment
-

Hyperlipidemia 48-160 mg oral QD CrCl 50-90 ml/min: Contraindicated

Fenofibrate May adjust dose start 48-54 mg QD if CrCl <50 ml/min
q 4-8 weeks or hepatic impairment

Hyperlipidemia 900-1,200 mg/day oral Contraindicated

if severe renal
impairment or hepatic
Gemfibrozil - dysfunction
Statins may increase
muscle toxicity: avoid
concomitant use

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Lipid lowering drugs (Cont.)
Drug Indications Dose
PCSK9 Inhibitors
Hypercholesterolaemia 140 mg s.c.
and mixed dyslipidaemia every 2 weeks
or 420 mg every month
Homozygous familial
hypercholesterolaemia Homozygous familial
Evolocumab hypercholesterolaemia:
420 mg s.c every month
Up-titrate to 420 mg
every 2 weeks if a
response is not achieved
Hypercholesterolaemia Start dose:
and mixed dyslipidaemia 75 mg s.c. every 2 weeks
Alirocumab
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
P.143
Dose adjustments Comments
Most common side
effects:
Nasopharingitis, upper
respiratory tract
infection, headache and
-
back pain
If a larger LDL-C reduction (>60%) Most common side
is required, the start dose could effects:
be 150 mg every 2 weeks, or Upper respiratory tract
300 mg every 4 weeks signs and symptoms,
pruritus and injection site
The dose can be individualised reactions
based on LDL-C level, goal of
therapy, and response. Max dose:
150 mg once every 2 weeks
 Heart failure & hypertension 9
P.144
Drug Indications Dose Dose adjustments Comments
ACEI
HF Start: 6.25 mg oral TID CrCl >50 ml/min: 75-100% Check renal function,
Target dose: 50 mg TID of the normal dose electrolytes,
Captopril

CrCl 10-50 ml/min: 25-50% drug interactions

HTN Start: 12.5 mg oral BID CrCl <10 ml/min: 12.5%
Target dose: 25-50 mg TID
Major contraindications:
Max 450 mg/day
History of angioedema,
HF, HTN Start: 2.5 mg oral BID CrCl 30-80 ml/min: start 5 mg/day known bilateral renal artery
Enalapril

Target dose: 10-20 mg BID CrCl 10-30 ml/min: start 2.5 mg/day stenosis, pregnancy (risk)

HF Start: 2.5-5.0 mg oral QD CrCl 31-80 ml/min: start 5-10 mg/day

Target dose: 20-35 mg QD CrCl 10-30 ml/min: start 2.5-5 mg/day
Lisinopril

CrCl <10 ml/min: start 2.5 mg/day

HTN 10-20 mg oral QD

Max: 80 mg QD

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Heart failure & hypertension (Cont.) 9
P.145
Drug Indications Dose Dose adjustments Comments
HF Start: 2 mg oral QD CrCl >60 ml/min: start 4 mg/day Check renal function,
Perindopril

Target dose: 8 mg QD CrCl 31-60 ml/min: start 2 mg/day electrolytes,

CrCl 15-30 ml/min: drug interactions
HTN Start: 4 mg QD start 2 mg every other day
Max dose: 8 mg QD CrCl <15ml/min:
2 mg on the day of dialysis Major contraindications:
History of angioedema,
HF, HTN Start: 2.5 mg oral QD CrCl <40 ml/min: start 1.25 mg QD, known bilateral renal artery
Ramipril

Target dose: 5 mg BID max 5 mg/day stenosis, pregnancy (risk)

Caution in elderly and hepatic impairment

HF Start: 0.5 mg oral QD CrCl <30 ml/min or severe hepatic

Target dose: 4 mg QD impairment: start 0.5 mg
Trandolapril

HTN 2-4 mg oral QD CrCl <30 ml/min or severe hepatic

impairment: start 0.5 mg

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Heart failure & hypertension (Cont.) 9
P.146
Drug Indications Dose Dose adjustments Comments
ARB

HF, HTN Start: 4-8 mg oral QD If renal or hepatic impairment: If ACEI is not tolerated
Candesartan

Target dose: 32 mg QD start 4 mg/day Check renal function,

electrolytes, drug
interactions

Major contraindications:
HF Start: 50 mg oral QD CrCl <20 ml/min: 25 mg QD History of angioedema,
known bilateral renal artery
Losartan

Target dose: 150 mg QD Caution if hepatic impairment

stenosis, pregnancy (risk)
HTN 50-100 mg oral QD CrCl <20 ml/min: 25 mg QD
Caution if hepatic impairment

HF Start: 40 mg oral BID If mild-moderate hepatic impairment:

Valsartan

Target dose: 160 mg BID max dose 80 mg/day

HTN 80-160 mg QD If mild-moderate hepatic impairment:

max dose 80 mg/day

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Heart failure & hypertension (Cont.) 9
P.147
Drug Indications Dose Dose adjustments Comments
Neprilysin inhibitor/ARB

Symptomatic Start: 49 mg/51 mg Do not initiate if K >5.4 mmol/l Do not co-administer with an ACEI or ARB. It must not
chronic HF oral BID or SBP <100 mmHg be started for at least 36 hours after discontinuing
with reduced Target dose: an ACEI
Sacubitril/Valsartan

ejection 97 mg/103 mg BID Start dose of 24 mg/26 mg BID Contraindicated if history of angioedema related
fraction if SBP 100-110 mmHg to ACEI or ARB
or CrCl 30-60 ml/min
Hereditary or idiopathic angioedema
Concomitant use with aliskiren if diabetes mellitus
or renal impairment
Severe hepatic impairment, biliary cirrhosis and
cholestasis

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Heart failure & hypertension (Cont.) 9
P.148
Drug Indications Dose Dose adjustments Comments
Beta-blockers: Check 12 - lead ECG
HTN Start: 25 mg oral QD CrCl 10-50 ml/min: Major contraindications:
Atenolol

Usual dose: 50-100 mg QD decrease dose 50% asthma, 2nd or 3rd degree
CrCl <10 ml/min: AV block
decrease dose 75%

HF Start: 1.25 mg oral QD CrCl <20 ml/min:

Cardioselective (1)

Target dose: 10 mg QD max dose 10 mg QD

Bisoprolol

Hepatic impairment: avoid use

HTN Start: 2.5-5 mg oral QD
Usual dose: 5-10 mg QD
Max dose: 20 mg QD

HF Start: 12.5-25 mg oral QD Hepatic impairment: start with low

Target dose: 200 mg QD doses and titrate gradually
Metoprolol

HTN 100-400 mg QD
Max dose: 400 mg QD

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Heart failure & hypertension (Cont.) 9
P.149
Drug Indications Dose Dose adjustments Comments
Beta-blockers: Check 12- lead ECG
HF Start: 1.25 mg oral QD Renal impairment or elderly: start Major contraindications:
Cardioselective (2)

Target dose: 10 mg QD dose 2.5 mg QD, titrate to 5 mg QD asthma, 2nd or 3rd degree
Hepatic impairment: contraindicated AV block
Nebivolol

HTN Start: 2.5 mg oral QD

Usual dose: 5 mg QD

HF Start: 3.125 mg oral BID Caution in elderly

Target dose: 25-50 mg BID Contraindicated if hepatic
Non-cardioselective

impairment
Carvedilol

HTN Start: 12.5 mg oral QD

Usual dose: 25 mg QD
and max dose: 25 mg BID
or 50 mg QD

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Heart failure & hypertension (Cont.) 9
P.150
Drug Indications Dose Dose adjustments Comments
Other vasodilators
HTN Start: 5 mg oral QD, Elderly or secondary agent: Contraindicated if
Amlodipine

increase after 1-2 weeks start 2.5 mg QD cardiogenic shock, 2nd

Max: 10 mg/day Hepatic impairment: or 3rd degree AV block,
start 2.5 mg QD severe hypotension

HTN Extended-release form: Renal and hepatic impairment:

Nifedipine

Start 20 mg oral BID or TID caution advised

Max: 60 mg BID

HTN Immediate-release form: Start 40 mg oral TID in elderly Contraindicated if

Verapamil

Dose: 80-120 mg oral TID; or small stature patients bradycardia, HF, LVSD
Start: 80 mg TID;
Max: 480 mg/day

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Heart failure & hypertension (Cont.) 9
P.151
Drug Indications Dose Dose adjustments Comments
Loop diuretics

HF 20-40 mg i.v. bolus, continuous Anuria: contraindicated

Furosemide

100 mg/6h (adjust based on kidney Cirrhosis/ascites: caution advised

function and clinical findings;
monitor creatinine) -

HTN 10-40 mg oral BID

HF 10-20 mg oral or i.v. QD Hepatic impairment: initial dose

Torsemide

should be reduced by 50% and

dosage adjustments made cautiously -
HTN 5 mg oral or i.v. QD
Max 10 mg QD

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Heart failure & hypertension (Cont.) 9
P.152
Drug Indications Dose Dose adjustments Comments
Thiazides
Indapamide Hydrochlorothiazide Chlorthalidone

HF 50-100 mg oral QD Elderly: max dose 25 mg/day

MD: 25-50 mg QD CrCl <25 ml/min: avoid use -

HTN Start 12.5-25 mg oral QD; Elderly: max dose 25 mg/day

-
Max: 50 mg/day CrCl <25 ml/min: avoid use

HF 25-200 mg oral/day CrCl <25 ml/min: avoid use

Hepatic impairment: caution advised -

HTN Start 12.5-25 mg oral QD CrCl <25 ml/min: avoid use

MD: may increase to 50 mg oral Hepatic impairment: caution advised
as a single or 2 divided doses -

HTN Start 1.25 mg PO QAM x4weeks, CrCl <25 ml/min: avoid use

then increase dose if no response Hepatic impairment: caution advised
Max: 5 mg/day -

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Heart failure & hypertension (Cont.) 9
P.153
Drug Indications Dose Dose adjustments Comments
Aldosterone-antagonists
HF Start 25 mg oral QD CrCl <10 ml/min, anuria or acute Check renal function,
Spironolactone

Target dose: 25-50 mg QD renal impairment: contraindicated electrolytes, drug

Severe hepatic impairment interactions
HTN 50-100 mg/day oral and elderly: caution advised Produces gynecomastia

HF Start 25 mg oral QD Elderly: caution advised Check renal function,

Eplerenone

Target dose: 50 mg QD CrCl <50 ml/min: contraindicated electrolytes, drug

interactions
HTN 50 mg oral QD-BID Major contraindications:
Max: 100 mg/day strong CYP3A4 inhibitors

Others
HF 5-7.5 mg oral BID Caution in elderly Contraindicated if severe
Ivabradine

and CrCl <15ml/min hepatic impairment

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Inotropics & vasopressors 9
P.154
Drug Indications Dose Dose adjustments Comments
HF/cardiogenic LD: 6 to 12 μg/kg i.v. Avoid use if CrCl <30 ml/min or Calcium sensitizer and ATP-dependent
Levosimendan

shock over 10 min (given only severe hepatic impairment potassium channel opener
if immediate effect is
needed) followed by
0.05 to 0.2 μg/kg/min
as a continuous infusion
for 24h
HF/cardiogenic 50 μg/kg i.v. in 10-20 min, Renal: Same bolus. Adjust infusion: Phosphodiesterase inhibitor
shock continuous 0.375- CrCl 50 ml/min: start 0.43 μg/kg/min Caution if atrial flutter
Milrinone

0.75 μg/kg/min CrCl 40 ml/min: start 0.38 μg/kg/min

CrCl 30 ml/min: start 0.33 μg/kg/min Hypotensive drug
ß effect

CrCl 20 ml/min: start 0.28 μg/kg/min

CrCl 10 ml/min: start 0.23 μg/kg/min
CrCl 5 ml/min: start 0.20 μg/kg/min
Cardiogenic 0.5-5 μg/min (0.25-2.5ml ß1, ß2 agonist
Isoproterenol
Isoprenaline/

shock of a 1:250,000 dilution) Contraindicated in patients with

i.v. infusion tachyarrhythmia, tachycardia or heart
- block caused by digitalis intoxication,
Bradyarrhythmias Bolus: 20-40 μg i.v.
Infusion: 0.5 μg/min of ventricular arrhythmias which require
2 mg/100 ml normal saline inotropic therapy, angina pectoris, recent
ACS, hyperthyroidism
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Inotropics & vasopressors (Cont.) 9
P.155
Drug Indications Dose Dose adjustments Comments
Cardiogenic 2-20 μg/kg/min i.v. ß1, a1/ß2 agonist
Dobutamine

shock Increases contractility with little effect

- on heart rate and blood pressure.
Reduces pulmonary and systemic VR,
PCP

Cardiogenic Dopaminergic effect: ß, a, dopaminergic agonist

Dopamine

shock 2-5 μg/Kg/min i.v. Increases BP, PAP, heart rate, cardiac

ß effect : 5-15 μg/Kg/min i.v.
a effect : 15-40 μg/Kg/min i.v.
Cardiogenic 0.05-0.2 μg/kg/min i.v.
Noradrenaline
- output and pulmonary and systemic VR
More arrhythmogenic than dobutamine
and noradrenaline
a 1, ß1 agonist

shock titrate to effect Increases BP and PAP

- Little arrhythmogenic
a effect

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Antiarrhythmics 9
P.156
Drug Indications Dose Dose adjustments Comments
Group I
AF 15-18 mg/kg i.v. over 60min, followed by Reduce LD to 12 mg/kg in severe renal Hypotension
Procainamide

(termination); infusion of 1-4 mg/min impairment (negative inotropic agent)

stable VT Reduce MD by one-third in moderate Lupus-like syndrome
i.v.

(with a pulse) renal impairment and by two-thirds in

severe renal impairment Contraindicated if myasthenia
Caution in elderly and asthma gravis, AV block, severe renal
impairment

Pulseless 1-1.5 mg/kg i.v./i.o. bolus (can give
VT/VF additional 0.5-0.75 mg/kg i.v./i.o. push
every 5-10 min if persistent VT/VF, max
cumulative dose = 3 mg/kg), followed
Lidocaine
1-2 mg/min infusion if liver disease Contraindicated if advanced
or HF AV block, bradycardia,
hypersensitivity to local

anesthetics
by infusion of 1-4 mg/min
Caution in HF, renal
i.v.

Stable VT 1-1.5 mg/kg i.v. bolus (can give additional impairment and elderly
(with a pulse) 0.5-0.75 mg/kg i.v. push every 5-10 min May cause seizures, psychosis
if persistent VT, max cumulative dose
= 3 mg/kg), followed by infusion Stop if QRS widens >50%
of 1-4 mg/min

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Antiarrhythmics (Cont.) 9
P.157
Drug Indications Dose Dose adjustments Comments
Group I
SVT, 2 mg/kg (max 150 mg) i.v. over 30 min Severe renal impairment: caution Contraindicated if cardiogenic
ventricular This may be followed by an infusion at advised shock, recent MI, 2nd or 3rd
arrhythmias a rate of 1.5 mg/kg/h for 1 h, reduced to degree AV block
Flecainide

0.1-0.25 mg/kg/h for up to 24h,

i.v.

max cumulative dose = 600 mg

PSVT, LD: 0.5-2 mg/kg i.v. direct over May need to reduce dose in renal Contraindicated if unstable
ventricular aminimum of 3-5min or hepatic failure HF, cardiogenic shock,
Propafenone

arrhythmias MD: 0.5-2.5 mg/kg i.v. direct q8h AV block, bradycardia,

(max 560 mg/day) myasthenia gravis
i.v.

or continuous infusion up to 23 mg/h severe hypotension,

bronchospastic disorders,
Brugada syndrome

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Antiarrhythmics (Cont.) 9
P.158
Dose
Drug Indications Dose Comments
adjustments
Group II
Arrhythmias 2.5 mg i.v. over 2.5 min every 5 min Caution in Contraindicated if cardiogenic shock, bradycardia
Atenolol

(max 10 mg) elderly and/or and greater than first-degree block, unstable HF
i.v.

severe renal
impairment

Arrhythmias 2.5-5 mg i.v. over 5min, Caution if Contraindicated if cardiogenic shock, bradycardia
Metoprolol

may repeat every 5 min severe hepatic and greater than first-degree block, unstable HF
(max 15 mg) impairment
i.v.

Arrhythmias Initially given as slow i.v. boluses of Contraindicated if cardiogenic shock, bradycardia
Propranolol

1 mg, repeated at 2 min intervals and greater than first-degree block, asthma,
(max: 10 mg in conscious patients unstable HF
i.v.

-
and 5 mg if under anesthesia)

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Antiarrhythmics (Cont.) 9
P.159
Dose
Drug Indications Dose Comments
adjustments
Group III
AF (termination) 5 mg/Kg i.v. over 30min, followed Reduce infusion rate if bradycardia, AV block,
by infusion of 1 mg/min for 6h, - hypotension
then 0.5 mg/min
Bolus should be avoided if hypotension or severe
Amiodarone

Stable VT 150 mg i.v. over 10 min followed by LV dysfunction

(with a pulse) infusion of 1 mg/min for 6h, then -
i.v.

0.5 mg/min Highly vesicant agent

Pulseless VT/VF 300 mg bolus i.v. (can give additional
150 mg i.v. bolus if VF/VT persists)
-
followed by infusion of 900 mg
over 24h
Paroxysmal 400 mg oral BID Contraindicated if severe renal or liver
Dronedarone

or persistent AF dysfunction, LVSD, symptomatic HF, permanent AF,

prevention - bradycardia… (multiple contraindications)

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Antiarrhythmics (Cont.) 9
P.160
Dose
Drug Indications Dose Comments
adjustments
Group IV
PSVT; AF (rate control) 0.25 mg/kg i.v. over 2 min Hepatic
Diltiazem

(may repeat with 0.35 mg/kg i.v. impairment:

i.v.

over 2 min), followed by infusion of caution advised -

5-15 mg/h

PSVT; AF (rate control) 2.5-5 mg i.v. over 2 min Contraindicated if AF+WPW, tachycardias QRS
(may repeat up to max cumulative (except RVOT-VT), fascicular VT, bronchospasm,
Verapamil

dose of 20 mg); can follow with age >70 years

i.v.

infusion of 2.5-10 mg/h -
Antidote:
- LVD: Calcium gluconate, dobutamine
- Bradycardia/AV block: Atropine, Isoproterenol
Rapid conversion to a Rapid i.v. boluses separated by Contraindicated if sick sinus syndrome, second or
normal sinus rhythm 2 min: 6 mg → 6 mg → 12 mg third degree Atrio-Ventricular (AV) block (except in
Adenosine

of PSVT including patients with a functioning artificial pacemaker),

i.v.

those associated - chronic obstructive lung disease with evidence of

with accessory by- bronchospasm (e.g. asthma bronchiale), long QT
pass tracts syndrome, severe hypotension; decompensated
(WPW syndrome) states of heart failure - Adenosine can cause AF

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Antiarrhythmics (Cont.) 9
P.161
Dose
Drug Indications Dose Comments
adjustments
Others
VT-Torsades Bolus: 1-2g i.v./i.o. over 5 min Caution if Contraindicated if myasthenia gravis
de Pointes Perfusion: 5-20 mg/min i.v. severe renal
Magnesium
sulfate

failure

Conversion 3 mg/kg i.v. over 10 min Contraindicated if ACS within the last 30 days,
of recent onset AF severe aortic stenosis, SBP <100 mmHg,
Vernakalant

If AF persists, a second 10min- HF class NYHA III/IV, severe bradycardia, sinus

infusion of 2 mg/kg, 15 min later node dysfunction or 2nd or 3rd degree heart
-
may be administered block, prolonged QT at baseline, use of i.v.
antiarrhythmics (class I and class III) within 4h
prior to, as well as in the first 4h after, vernakalant
administration

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Sedatives and neuropsychiatric drugs 9
P.162
Drug Indications Dose Dose adjustments Comments
Benzodiazepines: Use of benzodiazepines may lead to the development of physical and psychic dependence
upon these products. The risk of dependence increases with dose and duration of treatment. Benzodiazepines
may induce anterograde amnesia. Discontinuation: dosage should be reduced slowly
Short-acting benzodiazepines
Moderate or 250-500mcg oral TID as short as Elderly or debilitating Contraindicated if myasthenia gravis,
severe anxiety possible, increasing if required to a disease: 250mcg BID or TID severe respiratory insufficiency, sleep
Alprazolam

or anxiety total of 3 mg daily and gradually increased apnoea syndrome, severe hepatic
associated with if needed and tolerated insufficiency
depression Renal impairment
or mild-moderate hepatic
impairment: caution
Insomnia 1 mg oral at bedtime. This may Frail, debilitated or elderly: Contraindicated if acute pulmonary
be increased to 1.5 mg or 2 mg if start with half a tablet. Max insufficiency, severe respiratory
Loprazolam

necessary dose: 1 mg insufficiency, myasthenia gravis, phobic

Chronic pulmonary,
insufficiency, cerebrovascular
disease and chronic renal or
hepatic impairment: caution
or obsessional states and sleep apnoea
syndrome, monotherapy in depression
or anxiety associated with depression
and chronic psychosis and alcohol
intake

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Sedatives and neuropsychiatric drugs 9
P.163
Drug Indications Dose Dose adjustments Comments
Short-acting benzodiazepines
Severe anxiety Anxiety: 1-4 mg oral in divided doses Elderly: may respond Contraindicated if acute pulmonary
Premedication Insomnia: 1-2 mg oral before retiring to lower doses insufficiency, respiratory depression,
Lorazepam oral

before surgery Premedication before surgery: 2-3 mg Renal or hepatic sleep apnoea, obsessional states,
oral the night before operation 2-4 mg impairment: lower doses severe hepatic insufficiency,
oral 1-2h before the procedure may be sufficient myasthenia gravis

Pre-operative Premedication: 0.05 mg/Kg

Lorazepam injection

medication, acute By the i.v. route the injection should

anxiety states, be given 30-45 min before surgery
acute excitement By the i.m. route the injection should
or acute be given 1-1.5h before surgery
mania, status
Acute anxiety: 0.025-0.03 mg/kg
epilepticus
i.v./i.m. Repeat 6 hourly
Status epilepticus: 4 mg i.v.

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Sedatives and neuropsychiatric drugs (Cont.) 9
P.164
Drug Indications Dose Dose adjustments Comments
Short-acting benzodiazepines
Short-term 0.5-1.5 mg oral before retiring. The Elderly: may respond to Contraindicated if myasthenia gravis,
Lormetazepam oral

treatment of initial dosage may be increased to lower doses severe respiratory insufficiency, sleep
insomnia 2 mg in individual cases if this proves Chronic respiratory apnoea syndrome, acute intoxication
necessary insufficiency: a lower dose with alcohol, hypnotics, analgesics
is recommended or psychotropic drugs, severe liver
Severe renal impairment: insufficiency
caution

Insomnia DOSE / DOSE ADJUSTMENTS: 7.5-15 mg oral at bedtime

Midazolam oral

COMMENTS: Caution in adults >60years, chronically ill or debilitated patients, patients with chronic
respiratory insufficiency, patients with chronic renal failure, impaired hepatic function or with impaired
cardiac function - Contraindicated if conscious sedation in patients with severe respiratory failure or
acute respiratory depression - Severe cardiorespiratory adverse events have been reported (respiratory
depression, apnoea, respiratory arrest and/or cardiac arrest). Such life-threatening incidents are
more likely to occur when the injection is given too rapidly or when a high dosage is administered

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Sedatives and neuropsychiatric drugs (Cont.) 9
P.165
Drug Indications Dose Dose adjustments Comments
Short-acting benzodiazepines
Short-acting DOSE / DOSE ADJUSTMENTS:
sleep-inducing
drug Indications Adults <60 y Adults ≥60 y/debilitated or chronically ill
Conscious sedation i.v. Initial dose: 2-2.5 mg i.v Initial dose: 0.5-1 mg
Titration doses: 1 mg Titration doses: 0.5-1 mg
Midazolam injection (1)

Total dose: 3.5-7.5 mg Total dose: <3.5 mg

Anaesthesia i.v. 1-2 mg repeated i.v. Initial dose: 0.5 mg
premedication i.m. 0.07-0.1  mg/kg Slow uptitration as needed
i.m. 0.025-0.05  mg/kg

COMMENTS: Caution in adults >60years, chronically ill or debilitated patients, patients with chronic
respiratory insufficiency, patients with chronic renal failure, impaired hepatic function or with impaired
cardiac function - Contraindicated if conscious sedation in patients with severe respiratory failure or
acute respiratory depression - Severe cardiorespiratory adverse events have been reported (respiratory
depression, apnoea, respiratory arrest and/or cardiac arrest). Such life-threatening incidents are
more likely to occur when the injection is given too rapidly or when a high dosage is administered

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Sedatives and neuropsychiatric drugs (Cont.) 9
P.166
Drug Indications Dose Dose adjustments Comments
Short-acting DOSE / DOSE ADJUSTMENTS:
sleep-inducing
drug Indications Adults <60 y Adults ≥60 y/debilitated or chronically ill
Anaesthesia induction i.v. 0.15-0.2  mg/kg i.v. 0.05-0.15  mg/kg
(0.3-0.35 without premedication) (0.15-0.3 without premedication)
Midazolam injection (2)

Sedative component in i.v. Intermittent doses of 0.03-0.1 mg/kg i.v. Lower doses than recommended
combined anaesthesia or continuous infusion of for adults <60 years
0.03-0.1 mg/kg/h
Sedation in ICU i.v. LD: 0.03-0.3 mg/kg in increments of 1-2.5 mg
MD: 0.03-0.2 mg/kg/h

COMMENTS: Caution in adults >60years, chronically ill or debilitated patients, patients with chronic
respiratory insufficiency, patients with chronic renal failure, impaired hepatic function or with impaired
cardiac function - Contraindicated if conscious sedation in patients with severe respiratory failure or
acute respiratory depression - Severe cardiorespiratory adverse events have been reported (respiratory
depression, apnoea, respiratory arrest and/or cardiac arrest). Such life-threatening incidents are
more likely to occur when the injection is given too rapidly or when a high dosage is administered

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Sedatives and neuropsychiatric drugs (Cont.) 9
P.167
Dose
Drug Indications Dose Comments
adjustments
Long-acting benzodiazepines
Insomnia, 1.5-3 mg oral up to TID Elderly or hepatic Contraindicated if myasthenia gravis,
Bromazepam

short-term If a severe condition: 6-12 mg oral BID or TID impairment: severe hepatic impairment, severe
treatment lower doses are respiratory insufficiency, sleep apnoea
of anxiety or recommended syndrome
panic attacks

Anxiety, Anxiety: 20-30 mg oral daily in divided doses Elderly: lower doses Contraindicated if history of drug or
adjunctive or as a single dose given at night. Doses up to may be used alcohol dependence, myasthenia gravis,
therapy in 60 mg daily have been used in severe anxiety Chronic or acute severe respiratory insufficiency, sleep
epilepsy apnoea syndrome, severe hepatic
Clobazam

Epilepsy: starting dose of 20-30 mg oral per severe respiratory

day, increasing up to a max of 60 mg daily insufficiency, impairment
renal or hepatic
impairment:
lower doses are
recommended

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Sedatives and neuropsychiatric drugs (Cont.) 9
P.168
Dose
Drug Indications Dose Comments
adjustments
Long-acting benzodiazepines
Epileptic Oral: Initial dose not to exceed 1 mg/day; MD: Elderly: initial dose Contraindicated if acute pulmonary
disease and 4-8 mg should not exceed insufficiency, severe respiratory
Clonazepam

seizures i.v.: 1 mg by slow injection or slow infusion. 0.5 mg/day insufficiency, sleep apnoea syndrome,
Repeat dose if needed (1-4 mg are usually Chronic pulmonary myasthenia gravis, severe hepatic
sufficient) insufficiency, renal insufficiency, coma or in patients known
or mild-moderate to be abusing pharmaceuticals, drugs or
hepatic impairment: alcohol
may require lower
doses
Anxiety, 5-30 mg oral at bedtime Elderly, renal and Contraindicated if myasthenia gravis,
Clorazepate oral

insomnia or in divided doses hepatic impairment: severe decompensated respiratory

lower doses may be insufficiency, sleep apnoea syndrome,
required severe hepatic impairment
Caution if alcohol deprivation, give
thiamine before administering glucose
containing i.v. fluids

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Sedatives and neuropsychiatric drugs (Cont.) 9
P.169
Dose
Drug Indications Dose Comments
adjustments
Long-acting benzodiazepines
Agitation, Agitation, confusion, aggressiveness: Elderly, renal and Contraindicated if myasthenia gravis,
confusion, 20-200 mg/day, i.m./i.v. followed by oral therapy hepatic impairment: severe decompensated respiratory
Clorazepate

aggressiveness, lower doses may be insufficiency, sleep apnoea syndrome,

injection

Premedication: 20-50 mg/day i.m./i.v.

premedication, Alcoholism: 50-100 mg every 3-4h required severe hepatic impairment
tetanus, Benign tetanus (without tracheostomy) Caution if alcohol deprivation, give
alcoholism 120-500 mg/day i.v. thiamine before administering glucose
Malignant tetanus (with tracheostomy and containing i.v. fluids
assisted ventilation): 500-2,000 mg/day i.v.
Anxiety, Anxiety: starting dose 5 mg/day oral: usual Elderly and/or Contraindicated if acute pulmonary
Chlordiazepoxide

muscle spasm, dose up to 30 mg in divided doses increasing debilitated patients, insufficiency, sleep apnoea, respiratory
symptomatic to a max of 100 mg/day, in divided doses, renal or hepatic depression, phobic and obsessional
relief of adjusted on an individual basis impairment: dosage states, chronic psychosis, severe hepatic
acute alcohol Insomnia associated with anxiety: 10-30 mg should not exceed impairment, myasthenia gravis
withdrawal oral at bedtime half the adult dose
Muscle spasm: 10-30 mg/day oral in divided doses
Alcohol withdrawal: 25-100 mg, repeated
if necessary, in 2-4h

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Sedatives and neuropsychiatric drugs (Cont.) 9
P.170
Dose
Drug Indications Dose Comments
adjustments
Long-acting benzodiazepines
Anxiety 5-30 mg oral daily in divided doses Elderly and Contraindicated if phobic or
or debilitated obsessional states; chronic
10 mg i.v. or i.m. and repeated after an interval patients: half of the psychosis, hyperkinesis, acute
of not less than 4h recommended dose pulmonary insufficiency;
respiratory depression, acute
Diazepam (1)

0.5 mg/kg rectal Hepatic impairment or chronic severe respiratory

Dose can be repeated every 4-12h. Max 30 mg and severe renal insufficiency, myasthenia gravis,
impairment: sleep apnoea, severe hepatic
Insomnia associated 5-15 mg oral before retiring a lower dose is impairment, acute porphyria
with anxiety recommended
Cerebral palsy 5-60 mg oral daily in divided doses

Upper motor neuronic 5-60 mg oral daily in divided doses

spasticity

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Sedatives and neuropsychiatric drugs (Cont.) 9
P.171
Dose
Drug Indications Dose Comments
adjustments
Long-acting benzodiazepines
Muscle spasm 5-15 mg oral daily in divided doses or Elderly and Contraindicated if phobic or
10 mg i.v. or i.m. and repeated after after an debilitated obsessional states; chronic
interval of not less than 4h patients: half of the psychosis, hyperkinesis, acute
Diazepam (2)

0.5 mg/Kg rectal. Dose can be repeated every recommended dose pulmonary insufficiency;
4-12h. Max 30 mg respiratory depression, acute
Hepatic impairment or chronic severe respiratory
Tetanus 0.1-0.3 mg/Kg i.v. and repeated every 1-4h; and severe renal insufficiency, myasthenia gravis,
alternatively, a continuous infusion of 3-10 mg/ impairment: sleep apnoea, severe hepatic
kg/24h may be used. a lower dose is impairment, acute porphyria
0.5 mg/kg rectal. Dose can be repeated every recommended
4-12h. Max 30 mg

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Sedatives and neuropsychiatric drugs (Cont.) 9
P.172
Dose
Drug Indications Dose Comments
adjustments
Long-acting benzodiazepines
Epilepsy 2-60 mg oral daily in divided doses Elderly and Contraindicated if phobic or
or debilitated obsessional states; chronic
10-20 mg i.v.or i.m. The dose can be repeated if patients: half of the psychosis, hyperkinesis, acute
necessary after 30-60min. If indicated, this may recommended dose pulmonary insufficiency;
be followed by slow i.v. infusion (max total dose respiratory depression, acute
3 mg/kg over 24h) Hepatic impairment or chronic severe respiratory
Diazepam (3)

or and severe renal insufficiency, myasthenia gravis,

0.5 mg/kg rectal impairment: sleep apnoea, severe hepatic
Dose can be repeated every 4-12h. Max 30 mg a lower dose is impairment, acute porphyria
recommended
Alcohol withdrawal 5-20 mg oral, repeated if necessary in 2-4h
0.5 mg/kg rectal
Dose can be repeated every 4-12h. Max 30 mg
Delirium tremens: 10-20 mg i.v. or i.m.
Premedication 5-20 mg oral
before surgery

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Sedatives and neuropsychiatric drugs (Cont.) 9
P.173
Drug Indications Dose Dose adjustments Comments

Long-acting benzodiazepines
Insomnia 15 mg oral at bedtime. Elderly, chronic pulmonary Contraindicated if myasthenia
Flurazepam

insufficiency, renal or hepatic gravis, severe pulmonary

If severe insomnia: 30 mg oral but
residual effects on awakening are more
frequent at this dose
impairment: lower dose is
recommended
insufficiency, respiratory
depression, phobic or obsessional
states, chronic psychosis,
sleep apnoea, severe hepatic
insufficiency

Other sedatives
Management of 192 mg (1 capsule) oral TID Elderly, renal impairment, gross Contraindicated if acute
Clomethiazole (1)

restlessness and liver damage, decreased liver pulmonary insufficiency

agitation in the function, sleep apnoea and
elderly chronic pulmonary insufficiency: Alcohol combined with
caution clomethiazole particularly
Severe insomnia in 192-384 mg oral (1-2 capsules)
the elderly at bedtime in alcoholics with cirrhosis
can lead to fatal respiratory
depression even with short
term use

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Sedatives and neuropsychiatric drugs (Cont.) 9
P.174
Drug Indications Dose Dose adjustments Comments

Other sedatives
INDICATIONS: Alcohol withdrawal Elderly, renal impairment, gross Contraindicated if acute
Clomethiazole (2)

INITIAL DOSE : 2-4 capsules oral, if necessary repeated after some hours liver damage, decreased liver pulmonary insufficiency
function, sleep apnoea and Alcohol combined with
Day 1: first 24h: 9-12 capsules, Days 4-6: A gradual chronic pulmonary insufficiency: clomethiazole particularly
divided into 3 or 4 doses reduction in dosage until the caution in alcoholics with cirrhosis
Day 2: 6-8 capsules, final dose can lead to fatal respiratory
divided into 3 or 4 doses depression even with short
Administration for more than term use
Day 3: 4-6 capsules,
divided into 3 or 4 doses 9 days is not recommended

Sedation of adult ICU Switch to dexmedetomidine: initial i.v. Caution if hepatic impairment, The drug provides analgesia
Dexmedetomidine

patients infusion rate of 0.7 mcg/kg/h impaired peripheral autonomic and does not cause respiratory
Titrate upwards to achieve desired activity, pre-existing depression. Associated with a
level of sedation, bradycardia lower prevalence of ICU delirium
range 0.2-1.4 mcg/kg/h Frail patients: a lower starting compared to benzodiazepines.
Max dose: 1.4 mcg/kg/h infusion rate should be Primary adverse effects are
Max duration: 14 days considered dose-related bradycardia and
hypotension.
Dexmedetomidine should not
be administered by loading
or bolus dose

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Sedatives and neuropsychiatric drugs (Cont.) 9
P.175
Drug Indications Dose Dose adjustments Comments

Other sedatives
Insomnia 12.5-25 mg oral at bedtime Renal and hepatic impairment: Contraindicated if hypersensitive
Doxylamine

Max duration: 7 days caution to other antihistamines

Caution if: asthma, narrow angle
glaucoma, prostatic hypertrophy,
stenosing peptic ulcer, pyloric/
duodenal obstruction, bladder
neck obstruction, concurrent use
with MAOIs
Insomnia in patients 2 mg oral at bedtime Renal impairment: caution Do not use in patients
Melatonin

≥55 years Max duration: 13 weeks Hepatic impairment: with autoimmune diseases

not recommended Do not crush or chew tablets

Sedation during Initiate at 5 mcg/Kg/min i.v. Elderly: rate of infusion should Rapid onset (1-2 min) and short
intensive care (0.3 mcg/Kg/h) and titrate to achieve be reduced. Rapid bolus duration (3-5 min or longer if
sedation goals by 5 mcg/Kg/min administration is not indicated prolonged infusion)
Propofol

every 5 min in this group of patients Avoid loading doses because of

Maintenace rates of 5-50 mcg/Kg/ the risk of hypotension
min may be required Monitor blood lipid levels, blood
Avoid prolonged infusions pressure
>50 mcg/Kg/min Propofol has no analgesic
properties
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Sedatives and neuropsychiatric drugs (Cont.) 9
P.176
Drug Indications Dose Dose adjustments Comments

Other sedatives
Insomnia 10 mg oral at bedtime Elderly, debilitated patients, Contraindicated if obstructive
Zolpidem

Max duration: 4 weeks hepatic impairment: initial dose sleep apnoea, myasthenia
5 mg gravis, severe hepatic
insufficiency, acute and/or
severe respiratory depression
Insomnia 7.5 mg oral at bedtime Elderly, hepatic or renal Contraindicated if myasthenia
Zopiclone

Max duration: 4 weeks impairment: initial dose 3.75 mg gravis, severe sleep apnoea
syndrome, severe respiratory
or severe hepatic insufficiency

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Sedatives and neuropsychiatric drugs (Cont.) 9
P.177
Dose
Drug Indications Dose Comments
adjustments
Neuroleptics: Extrapyramidal symptoms and neuroleptic malignant syndrome may occur with all neuroleptics.
Elderly people with dementia who are treated with antipsychotics are at a small increased risk of death
compared with those who are not treated
Typical neuroleptics
Schizophrenia and Oral: Initially 25 mg TID or 75 mg at Elderly Contraindicated if liver or renal dysfunction,
other psychoses bedtime increasing by daily amounts of (schizophrenia, epilepsy, Parkinson, hypothyroidism, cardiac
25 mg to an effective MD (75-300 mg nausea and failure, phaeochromocytoma, agranulocytosis
daily, some patients may require up to 1g) vomiting): start myasthenia gravis, prostate hypertrophy,
Chlorpromazine

I.M.: 25-50 mg every 6-8h with ⅓ - ½ usual history of narrow angle glaucoma
adult dose Caution in patients with risk factor for stroke,
Intractable hiccup Oral: 25-50 mg TID or QD seizures, cardiovascular disease or a family
I.M.: 25-50 mg and if this fails 25-50 mg history of QT prolongation
by slow i.v. infusion
Nausea and Oral: 10-25 mg every 4-6h
vomiting in terminal I.M.: 25 mg initially then 25-50 mg every
illness 3-4h until vomiting stops, then change
to orally

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Sedatives and neuropsychiatric drugs (Cont.) 9
P.178
Dose
Drug Indications Dose Comments
adjustments
Typical neuroleptics
Schizophrenia and Patients without previous exposure of Elderly Contraindicated if comatose states, marked
other psychoses fluphenazine: start 12.5 mg i.m (over 60): cerebral atherosclerosis, liver failure, renal
Fluphenazine

Next dose depends on patient’s response
(12.5-100 mg)
When administered as maintenance
therapy, a single injection may be
effective for up to 4weeks or longer
a lower dose is failure, phaeochromocytoma, severe cardiac
recommended insufficiency, severely depressed states,
Liver and renal existing blood dyscrasias
disease: caution Caution if arrythmias, Parkinson, narrow angle
glaucoma, thyrotoxicosis, hypothyroidism,
epilepsy, myasthenia gravis, prostatic
hypertrophy, severe respiratory disease

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Sedatives and neuropsychiatric drugs (Cont.) 9
P.179
Drug Indications Dose Dose adjustments Comments

Typical neuroleptics
Schizophrenia, psychoses Acute phase: 2-20 mg/day oral as DOSE ADJUSTMENTS:
and mania a single dose or in divided doses Elderly: start with half the dosage stated for adults
Chronic phase: 1-3 mg oral TID, and adjusted according to the results if necessary
may be increased up to 20 mg/day
in divided doses, depending on the COMMENTS: Contraindicated if comatose states,
Haloperidol oral (1)

response CNS depression, Parkinson, lesions of the basal ganglia,

Max daily dose: 20 mg
Psychomotor Acute phase: Moderate
anti-agitation symptomatology 1.5-3.0 mg oral
BID or TID
Severe symptomatology/resistant
patients 3-5 mg oral BID or TID
Chronic phase: 0.5-1 mg oral TID,
may be increased to 2-3 mg TID,
if required, MD: gradually reduced
to the lowest effective MD
Max daily dose: 20 mg
clinical significant cardiac disorders, QT interval prolongation,
history of ventricular arrhythmia or Torsades de pointes,
clinically significant bradycardia, 2nd or 3rd degree heart block,
uncorrected hypokalaemia and use of other QT prolonging drugs
Caution if renal failure, liver disease, epilepsy, hyperthyroidism,
phaeochromocytoma
Bioavailability from the oral route is about 60% of that from
the i.m. route and readjustment of dose may be required
i.v. haloperidol can be associated with QT prolongation and
torsades de pointes

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Sedatives and neuropsychiatric drugs (Cont.)
Drug Indications
Typical neuroleptics
Gilles de la Tourette
Haloperidol
syndrome, severe tics,
oral (2)
intractable hiccup
Rapid control of the
symptoms of hostility,
Haloperidol injection
aggression, hyperactivity,
disruptive and violent
behaviour, confusion,
emotional withdrawal,
hallucinations and delusions
associated with acute and
chronic schizophrenia,
mania, and hypomania, and
organic brain syndrome
Nausea and vomiting
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
Dose
Starting dose 1.5 mg oral TID
adjusted according to response
A daily MD of 10 mg may be
required in Gilles de la Tourette
syndrome
Max daily dose: 20 mg
Initial doses of 2-10 mg i.m.
Depending on the response of the
patients, subsequent doses may
be given every 4-8h up to a max of
18 mg/day
9
P.180
Dose adjustments Comments
DOSE ADJUSTMENTS:
Elderly: start with half the dosage stated for adults
and adjusted according to the results if necessary
COMMENTS: Contraindicated if comatose states,
CNS depression, Parkinson, lesions of the basal ganglia,
clinical significant cardiac disorders, QT interval prolongation,
history of ventricular arrhythmia or Torsades de pointes,
clinically significant bradycardia, 2nd or 3rd degree heart block,
uncorrected hypokalaemia and use of other QT prolonging drugs
Caution if renal failure, liver disease, epilepsy, hyperthyroidism,
phaeochromocytoma
Bioavailability from the oral route is about 60% of that from
the i.m. route and readjustment of dose may be required
i.v. haloperidol can be associated with QT prolongation and
torsades de pointes
 Sedatives and neuropsychiatric drugs (Cont.) 9
P.181
Drug Indications Dose Dose adjustments Comments

Typical neuroleptics
Management of pain, 12.5-25 mg i.m. or i.v. injection. In Elderly: caution Caution if liver dysfunction
restlessness or cases of severe agitation, up to 50 mg or cardiac disease, bradycardia
Levomepromazine

distress in terminally may be used, repeated every 6-8h or 2nd or 3rd degree heart block,
ill patient or risk of QT interval prolongation
25-200 mg/day by continuos s.c. infusion
or
12.5-50 mg oral every 4-8h
Psychiatric Bed patients: initially the total
conditions daily dose 100-200 mg oral, usually
divided into 3 doses, gradually
increased to 1g daily if necessary

Anxiety, Severe conditions: Initially 75 mg/ Elderly Caution if liver or renal

psichiatric conditions day oral in divided doses. Titrate Severe conditions: Initially dysfunction, epilepsy, Parkinson,
Pericyazine

according to patient response at 15-30 mg/day in divided doses hypothyroidism, cardiac failure,

weekly intervals; MD: max dose Mild or moderate conditions: phaeochromocytoma, myasthenia
300 mg/day start 5-10 mg/day. Half or gravis, prostrate hypertrophy,
Mild or moderate conditions: Initially quarter the normal adult dose history of narrow angle
15-30 mg/day oral divided in two may be sufficient as MD glaucoma, agranulocytosis, risk
doses, with a larger dose being given of QT interval prolongation
in the evening Discontinue if unexplained fever
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Sedatives and neuropsychiatric drugs (Cont.) 9
P.182
Drug Indications Dose Dose adjustments Comments

Typical neuroleptics
Anxiety, psichiatric DOSE: 4 mg oral TID. Titrate according to DOSE ADJUSTMENTS:
conditions, nausea and patient response. Max daily dose: 24 mg Elderly: one quarter or one half of the recommended adult dosage
Perphenazine

vomiting, intractable
hiccup
COMMENTS: Contraindicated if leucopenia, or in association with drugs liable to cause bone marrow
depression, or to patients in comatose states - Caution if liver disease, severe respiratory disease,
renal failure, epilepsy, Parkinson, history of narrow angle glaucoma, hypothyroidism, myasthenia gravis,
phaeochromocytoma, prostatic hypertrophy, risk of QT interval prolongation

Schizophrenia, DOSE: DOSE ADJUSTMENTS:

other psychoses Chronic schizophrenia: 2-20 mg oral Elderly: half the normal starting dose
daily, with 2 mg as a starting dose Caution if hepatic, renal impairment or phaeochromocytoma
This may be increased according to
Pimozide

response and tolerance
COMMENTS: Contraindicated if risk of QT interval prolongation,
known uncorrected hypokalaemia, hypomagnesaemia, clinically
Other psychoses: an initial dose
significant cardiac disorders, clinically significant bradycardia,
of 4 mg oral daily which may then
severe central nervous system depression, depression,
be gradually increased, if necessary,
Parkinson, concomitant use with CYP3A4 or CYP2D6 inhibiting
according to response, max 16 mg
drugs, serotonin uptake inhibitors
daily
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Sedatives and neuropsychiatric drugs (Cont.) 9
P.183
Drug Indications Dose Dose adjustments Comments

Typical neuroleptics
Anxiety, depressive Low dosage: 2-4 mg/day oral, given DOSE ADJUSTMENTS:
Trifluoperazine

symptoms, agitation, in divided doses, according to the
nausea and vomiting severity of the patient’s condition
High dosage: 5 mg oral BID, after a
week this may be increased to 15 mg/
day. If necessary, further increases
of 5 mg may be made at three-day
intervals
Elderly: starting dose should be reduced by at least half
COMMENTS: Contraindicated if comatose patients, existing
blood dyscrasias or known liver damage, uncontrolled cardiac
decompensation
Caution if CV disease , Parkinson, risk of QT interval prolongation

Acute psychoses 50-150 mg i.m., repeated if necessary DOSE ADJUSTMENTS:

after 2-3 days Elderly, renal or hepatic impairment: caution, a lower dose may be
necessary
Zuclopenthixol

Some patients may need an

additional injection between 1-2 days
after the first injection
Max accumulated dosage: 400 mg
COMMENTS: Contraindicated if circulatory collapse, depressed
level of consciousness
Caution if Parkinson, epilepsy, risk of QT interval prolongation,
cardiac disease, or arrhythmias, narrow angle glaucoma,
myasthenia gravis, prostatic hypertrophy, hypothyroidism,
hyperthyroidism, phaeochromocytoma

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Sedatives and neuropsychiatric drugs (Cont.) 9
P.184
Drug Indications Dose Dose adjustments Comments
Atypical neuroleptics: 3 differences with typical neuroleptics: the risk of extrapyramidal symptoms is lower,
tardive dyskinesia is reduced and the ability to block serotonin-2 receptors is present. Atypical neuroleptics
have been associated with new-onset diabetes and metabolic syndrome
Schizophrenia For acute psychotic episodes: Elderly: caution Contraindicated if concomitant
Amisulpride

400-800 mg/day oral CrCl 30-60 ml/min: prolactin-dependent tumours,

In individual cases, the daily dose may
be increased up to 1,200 mg/day
Doses should be adjusted individually
Administered QD at oral doses up
to 300 mg, higher doses BID
Severe manic 5 mg s.l. BID
Asenapine
reduce to a half
CrCl 10-30 ml/min:
reduce to a third
Elderly, moderate hepatic
phaeochromocytoma, combination
with levodopa
Caution if epilepsy, risk of QT
interval prolongation
Caution if Parkinson, risk of QT interval

episodes The dose can be increased to 10 mg BID impairment: caution prolongation, seizures
associated with based on individual clinical response Do not use in severe hepatic
bipolar type I and tolerability impairment or CrCl <15ml/min
disorder Do not chew or swallow tablets

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Sedatives and neuropsychiatric drugs (Cont.) 9
P.185
Drug Indications Dose Dose adjustments Comments

Atypical neuroleptics
Schizophrenia, Oral: 10-15 mg QD with a MD Caution if elderly, severe Orodispersible tablet should be placed
manic episodes of 10-30 mg QD hepatic impairment in the mouth, it will rapidly disperse
in saliva
Aripiprazole

in bipolar type I i.m.: Recommended initial dose:

disorder 9.75 mg Dose range: 5.25-15 mg
A second injection may be administered
2h after the first injection, on the basis
of individual clinical status and no more
than three injections should be given in
any 24h period
Max daily dose: 30 mg/day
Psichiatric Schizophrenia: recommended starting
conditions dose 10 mg/day orally
Olanzapine
Caution if known CV disease,
history of QT prolongation, epilepsy,
concomitant administration of potent
CYP3A4 or CYP2D6 inhibitors
Elderly, renal or hepatic Contraindicated if risk of narrow-angle
impairment: consider glaucoma

a lower starting dose Caution if Parkinson, low leukocyte and/

Manic episode:
Starting dose 15 mg QD oral
in monotherapy or 10 mg QD
in combination therapy. Then, adjust
dose according to response:
5-20 mg/day
(5 mg/day) or neutrophil counts for any reason,
risk of QT interval prolongation
Orodispersible tablet should be placed
in the mouth, it will rapidly disperse
in saliva

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Sedatives and neuropsychiatric drugs (Cont.) 9
P.186
Drug Indications Dose Dose adjustments Comments

Atypical neuroleptics
Schizophrenia, 6 mg oral QD, administered in the Caution if elderly patients Caution if severe hepatic impairment,
schizoaffective morning. Some patients may benefit with dementia with risk seizures, Parkinson, risk of QT interval
disorder from lower or higher doses within the factors for stroke prolongation, low leukocyte and/
recommended range of 3-12 mg QD Mild renal impairment: or neutrophil counts for any reason,
Paliperidone

(6-12 mg for schizoaffective disorder) initial dose 3 mg QD
(max 6 mg)
Moderate-severe renal
impairment:
initial dose 1.5 mg QD
(max 3 mg)
CrCl <10 ml/min:
not recommended
known CV disease, cerebrovascular
disease or conditions that predispose
the patient to hypotension
Do not chew, divide, or crush
Take it the same way with regard
to meals

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Sedatives and neuropsychiatric drugs (Cont.) 9
P.187
Dose
Drug Indications Dose Comments
adjustments
Atypical neuroleptics
Schizophrenia IRF: Total daily dose for the first 4 days is: 50 mg (Day 1), 100 mg DOSE ADJUSTMENTS:
(Day 2), 200 mg (Day 3) and 300 mg (Day 4), then 150-750 mg/day Elderly, hepatic impairment: caution,
Administered in 2 divided doses a lower dose may be necessary
PRF: Starting dose 300 mg oral on Day 1 and 600 mg on Day 2
MD: 400-800 mg/day
COMMENTS: Contraindicated if
Moderate-severe IRF: Total daily dose for the first 4 days is: 100 mg (Day 1), 200 mg concomitant administration of
manic episodes (Day 2), 300 mg (Day 3) and 400 mg (Day 4) cytochrome P450 3A4 inhibitors,
in bipolar Further dosage adjustments up to 800 mg/day
such as HIV-protease inhibitors, azole-
Quetiapine

disorder Administered in 2 divided doses

PRF: Starting dose 300 mg oral on Day 1 and 600 mg on Day 2 antifungal agents, erythromycin,
MD: 400-800 mg/day clarithromycin and nefazodone
Caution if low leukocyte and/or neutrophil
Depression IRF: Total daily dose for the first 4days is: 50 mg (Day 1), 100 mg
in bipolar (Day 2), 200 mg (Day 3) and 300 mg (Day 4) counts for any reason, history of seizures,
disorders The recommended daily dose is 300 mg cerebrovascular disease, cardiovascular
Administered at bedtime disease, risk of QT interval prolongation
PRF: Total daily dose for the first 4 days is: 50 mg oral (Day 1), It could be used if Parkinson disease
100 mg (Day 2), 200 mg (Day 3) and 300 mg (Day 4)
Recommended daily dose: 300 mg PRF: tablets should not be split,
chewed or crushed
Major depressive PRF: 50 mg on Day 1 and 2, and 150 mg on Day 3 and 4 at bedtime
episodes Max dose 300 mg/day
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Sedatives and neuropsychiatric drugs (Cont.) 9
P.188
Drug Indications Dose Dose adjustments Comments

Atypical neuroleptics
Schizophrenia Start 2 mg/day oral (QD or in 2 divided doses) Elderly: 0.5 mg BID Caution if known
The dosage may be increased on the 2nd day to 4 mg Caution if renal or cardiovascular disease,
MD: 4-6 mg hepatic impairment low leukocyte and/or
neutrophil counts for any
Manic episodes Start with 2 mg oral QD Elderly: start with reason, Parkinson, risk of
in bipolar disorder Dosage adjustments, if needed, should occur 0.5 mg BID QT interval prolongation
Risperidone (1)

at intervals of not less than 24h and in dosage This dosage can be Orodispersable tablet:
increments of 1 mg/day. Max daily dose 6 mg individually adjusted place the tablet on the
with 0.5 mg BID tongue
increments to
1-2 mg BID
Caution if renal
or hepatic impairment
Persistent aggression in Start with 0.25 mg oral BID Caution if renal
patients with moderate This dosage can be individually adjusted by or hepatic impairment
to severe Alzheimer’s increments of 0.25 mg BID, not more frequently
dementia than every other day, if needed. Optimum dose is
0.5 mg BID for most patients

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Sedatives and neuropsychiatric drugs (Cont.) 9
P.189
Drug Indications Dose Dose adjustments Comments

Atypical neuroleptics
Conduct disorder ≥50kg: starting dose 0.5 mg oral QD Caution if renal or Caution if known
Risperidone (2)

This dosage can be individually adjusted by hepatic impairment cardiovascular disease,

increments of 0.5 mg QD not more frequently low leukocyte and/or
than every other day, if needed. Optimum dose is neutrophil counts for any
1 mg QD for most patients reason, Parkinson, risk of
<50kg: starting dose 0.25 mg oral QD QT interval prolongation
This dosage can be individually adjusted by Orodispersable tablet:
increments of 0.25 mg QD not more frequently place the tablet on the
than every other day, if needed. Optimum dose tongue
is 0.5 mg QD
Acute and chronic Starting dose: 400-800 mg oral daily, given as Renal impairment: Contraindicated if
schizophrenia one or two tablets twice daily (morning and early caution phaeochromocytoma
evening) and acute porphyria,
Predominantly positive symptons: starting concomitant prolactin-
Sulpiride

dose of at least 400 mg oral BID, increasing dependent tumours,

if necessary up to a max of 1,200 mg BID association with levodopa
Predominantly negative symptoms respond to or antiparkinsonian drugs
doses below 800 mg oral daily, a starting dose Caution if Parkinson,
of 400 mg BID is recommended epilepsy, low leukocyte
Patients with mixed positive and negative and/or neutrophil counts
symptoms: 400-600 mg oral BID for any reason, risk of QT
interval prolongation

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
 Sedatives and neuropsychiatric drugs (Cont.)
Drug Indications Dose
Atypical neuroleptics
Behavioral disorders Starting dose 50 mg oral/i.m./i.v.
in dementia patients BID, increasing if necessary
to 100 mg TID
Tiapride
Max dose 400 mg/day
Huntington’s disease 1,200 mg/day oral/i.m./i.v. divided
in 3 doses
Progressive reduction to a MD
Schizophrenia Initial dose 40 mg oral BID
Bipolar type I disorder with food
Then, dose may be increased
Ziprasidone
to 60-80 mg BID
Max dose 80 mg BID
Acute treatment 10-20 mg i.m. administered as
of agitation in required up to a max dose of
schizophrenia 40 mg/day
Doses of 10 mg may be
administered every 2h
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional
to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
Dose adjustments
Elderly: caution
CrCl 30-60 ml/min:
75% of the normal dose
CrCl 10-30 ml/min:
50% of the normal dose
CrCl <10 ml/min:
25% of the normal dose
Elderly, renal or hepatic
impairment: caution, a lower
dose may be necessary
9
P.190
Comments
Contraindicated if phaeochromocytoma,
concomitant prolactin-dependent
tumours, association with levodopa
or antiparkinsonian drugs
Caution if epilepsy, Parkinson, low
leukocyte and/or neutrophil counts
for any reason, risk of QT interval
prolongation
Contraindicated if known history of
QT prolongation, decompensated
heart failure, recent MI
It could the parenteral drug of choice
for patients with Parkinson disease
 Abbreviations
APTT = Activated partial thromboplastin time
AB = Airway and breathing
ABG = Arterial blood gas
AADs = Antiarrhythmic drugs
AAS = Acute aortic syndrome
ACEI = Angiotensin converting enzyme inhibitor
ACLS = Advanced cardiovascular life support
ACS = Acute coronary syndrome
ACT = Activated clotting time
AD = Aortic Dissection
AED = Automated external defibrillator
AF = Atrial fibrillation
Ao = Aortic
aPTT = Activated partial thromboplastin time
ARB = Angiotensin receptor blockers
AS = Aortic stenosis
AV = Atrioventricular
AVN = Atrioventricular node
AVNRT = Atrioventricular nodal re-entrant
tachycardia
AVNT = Atrioventricular nodal tachycardia
BID = Twice a day
BBB = Bundle branch block
BLS = Basic life support P.191
BNP = Brain natriuretic peptide
BP = Blood pressure
CABG = Coronary artery bypass grafting
CAD = Coronary artery disease
Cath Lab = Catheterisation laboratory
CCB = Calcium channel blockers
CCU = Coronary care unit
CHF = Congestive heart failure
CMR = Cardiovascular magnetic resonance
COPD = Chronic obstructive pulmonary disease
CPAP = Continuous positive airway pressure
CPR = Cardiopulmonary resuscitation
Cr = Creatinine blood level (mg/dL)
CrCl = Creatinine clearance
CS = Cardiogenic shock
CSM = Carotid sinus massage
CSNRT = Corrected sinus node recovery time
CSS = Carotid sinus syndrome
CT = Computed tomography
CT-angio = Computed tomography angiography
cTn = Cardiac troponin
CUS = Compression venous ultrasound
 Abbreviations (Cont.)
CV = Cardiovascular
CVA = Cerebrovascular accident
CXR = Chest X-ray
DAPT = Dual antiplatelet therapy
DD = Dyastolic dysfunction
DM = Diabetes mellitus
dTT = Diluted thrombin time
DVT = Deep vein thrombosis
ECG = Electrocardiogram
ECT = Ecarin clotting time
ED = Emergency department
EG = Electrograms
eGFR = E stimated glomerular filtration rate
(ml/min/1.73 m2)
EMB = Endomyocardial biopsy
EMS = Emergency medical services
EPS = Electrophysiological study
ERC = European Resuscitation Council
ESR = Erythrocyte sedimentation rate
ETT = Exercice treadmill testing
FFP = Fresh frozen plasma
FMC = First medical contact
GER = Gastroesophageal reflux P.192
GFR = Glomerular flow rate
GI = Gastrointestinal
GP = Glycoprotein
Hb = haemoglobin
HF = Heart failure
HIT = Heparin-induced thrombocytopenia
HOCM = Hypertrophic obstructive cardiomyopathy
HTN = Hypertension
HR = Heart rate
hsTn = High-sensitive troponin
IABP = Intra-aortic balloon pump
ICC = Intensive cardiac care
ICCU = Intensive cardiac care unit
ICD = Implantable cardioverter defibrillator
IHD = Ischemic heart disease
IMH = Intramural hematoma
IRF = Immediate-release formulation
ISFC = International Society and Federation
of Cardiology
i.o. = Intraosseous
IV = Invasive ventilation
 Abbreviations (Cont.)
i.v. = Intravenous
KD = Kidney disease
LBBB = Left bundle branch block
LD = Loading dose
LGE = Late gadolinium enhancement
LMWH = Low-molecular weight heparin
LOC = Loss of consciousness
LV = Left ventricular
LVD = Left ventricular dysfunction
LVEF = Left ventricular ejection fraction
LVH = Left ventricular hypertrophy
LVSD = Left ventricular systolic dysfunction
MCS = Mechanical circulatory support
MD = Maintenance dose
MDCT = Computed tomography with >4 elements
MI = Myocardial infarction
MRA = Mineralocorticoid receptor antagonist
MRI = Magnetic resonance imaging
Mvo = Microvascular obstruction
NIV = Non-invasive ventilation
NOAC = New oral anticoagulants
NSAID = N  on-steroidal anti-inflammatory drugs
NSTE-ACS = Non ST-segment elevation P.193
acute coronary syndrome
NSTEMI = Non ST-segment elevation myocardial infarction
NTG = Nitroglycerin
NT-proBNP = N-terminal pro brain natriuretic
peptide
NVAF = Non-valvular atrial fibrillation
NYHA = New York Heart Association
OH = Orthostatic hypotension
PAP = Pulmonary arterial pressure
PAU = Penetrating aortic ulcer
PCI = Percutaneous coronary intervention
PCM = Physical counter-measures
PCP = Pulmonary capillary pressure
PE = Pulmonary embolism
PEA = Pulmonary endarterectomy
PEEP = Positive end expiratory pressure
PPC = Prothrombin complex concentrate
PR = Pulmonary regurgitation
PRECISE-DAPT = PREdicting bleeding Complications
In patients undergoing Stent
implantation and subsEquent Dual
Anti Platelet Therapy
 Abbreviations (Cont.)
PRF = Prolonged-release formulation
ProCT = Procalcitonin
PRN = Pro re nata
PS-PEEP = Pressure support-positive end-
expiratory pressure
PSVT = Paroxysmal supraventricular tachycardia
QD = Once a day
QPM = Every evening
rFVIIa = Recombinant factor VIIa
rtPA = Recombinant tissue plasminogen activator
RV = Right ventricular
RVOT-VT = Right ventricular outflow tract
ventricular tachycardia
SBP = Systemic blood pressure
s.c = Subcutaneous
SIRS = systemic inflammatory response syndrome
SLE = Systemic lupus erythematosus
SMU = Syncope management units
STE-ACS = S  T-segment elevation acute
coronary syndrome
STEMI = ST-segment elevation myocardial
infarction
SVT = Supraventricular tachycardia P.194
Spo2 = Oxygen saturation
TEE = Transesophageal echocardiography
TEVAR = T horacic endovascular aortic repair
TIA = Transient ischemic attack
TID = Three times a day
TLOC = Transient loss of consciousness
TOE = Transoesopageal echocardiography
TSH = Thyroid-stimulating hormone
TTE = Transthoracic echocardiography
UA = Unstable angina
UFH = Unfractionated heparin
ULN = Upper limit of normal
VF = Ventricular fibrillation
VR = Vascular resistance
VT = Ventricular tachycardia
VTE = Venous thromboembolism
VVS = Vasovagal syncope
WBC = white blood cell count
WHO = World Health Organization
WPW = Wolff-Parkinson-White
 Notes
P.195
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 Notes
P.196
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Disclaimer and Copyrights
This is a publication of the Acute Cardiovascular Care Association (ACCA), a branch of the
European Society of Cardiology. Its content reflects the opinion of the authors based on the
evidence available at the time it was written and does not necessarily imply an endorsement
by ACCA or the ESC.
The guidance suggested in the Clinical Decision Making Toolkit does not override the
individual responsibility of the healthcare professional to make appropriate decisions
according to each patient’s circumstances and profile, as well as local regulations
and licenses.
Some content, illustrations/tables/figures were inspired and/or adapted from ESC Guidelines
and other existing sources, with permission granted by the original publishers.

Acknowledgements
We are indebted to all the authors for their commitment and for the strong effort to
synthesise their wide scientific knowledge and clinical experience into simple algorithms
and schemes using the aim to help clinicians in everyday clinical practice in the easiest
possible manner as the main driver of their work.
The support of this initiative by the ACCA board members was essential to launch this
initiative as was the hard work of the ESC staff to make this project move forward.

January 2018
 Clinical Decision Making TOOLKIT
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2018 edition www.escardio.org/ACCA