Optimizing The use of Anticoagulant in

Acute Coronary Syndrome

Mohammad Saifur Rohman1,2

1. Brawijaya Cardiovascular Research Center

2. Department of Cardiology and Vascular Medicine, Faculty of
Medicine, Brawijaya University/Dr. Saiful Anwar Hospital, Malang
 Chest pain

ST elevation ST depression
ECG ST segment

Bio-chemistry Troponin rise / Troponin

fall normal

NSTEACS
Diagnosis

STEACS-STEMI NSTEMI UA
Adapted from Hamm CW et al. Eur Heart J 2011;32:2999 – 3054
2
 Thrombosis induced ACS
Acute thrombosis induced by a ruptured or eroded atherosclerotic
coronary plaque, with or without concomitant vasoconstriction,
causing a sudden and critical reduction in blood flow

Hamm CW et al. EurHeart J 2011;32:2999 –3054; Bentzon JF et al. Circ Res. 2014;114:1852-1866
3
 GRACE REGISTRY
STEMI
Higher mortality 6
months after discharge
NSTEMI
in NSTEMI vs STEMI –
aggressive long term
management
UA

NSTEMI
Higher in hospital
STEMI
mortality of
UA
STEMI vs NSTEMI
- need urgent
treatment
Fox KAA et al. BMJ 2006;333:1091-1094
 Acute Coronary Syndrome (ACS)
A Major Cause of Mortality and Morbidity
UA/NSTEMI
• In-hospital death and re-infarction: 5-10%1
• Six-month mortality in the GRACE registry2 (from admission to 6
months):
- NSTEMI: 13%
- UA: 8%
STEMI
• 1/3 of STEMI patients will die within 24 h of the onset of ischemia1
• In-hospital death and reinfarction: 8-10%3
• One-month mortality: 6-7%4
1.Grech & Ramsdale. Acute coronary syndrome : unstable angina and non-ST segment elevation myocardial infarction. BMJ 2003;326:1259-61;
2. Fox. et al. An international on acute coronary syndrome care: Insight from the global registry of acute coronary event
Am Heart. Et al J 2004:148:S40-5;
3.Antman et al. ACC/AHA guideline for the management of patiets with ST-Elevation Myocardial infarction. Circulation 2004;110:e82-292;
4.van de Werf et al. Management of acute myocardial infarction in patients presenting with ST-segment Elevation. Eur Heart J 2003;24:28-66
 STEMI Management
STEMI Diagnosis

EMS or non primary-PCI

Primary-PCI capable center capable center

Preferably < PCI possible < 120 min?

60 min
Immediate transfer to PCI
center
Primary-PCI Yes No
Preferably ≤ 90 min
(≤ 60 min in early presenters) Preferably ≤
Rescue-PCI
30 min
Immediately Immediate transfer to PCI
center
No Succesful Immediate
fibrinolysis ? fibrinolysis ?
Yes
Heparin Preferably 3-24 h
Coronary angiography Steg G et al. Eur Heart J. 2012;33:2569-619
6
Time to Treatment is Critical in STEMI

Mensah GA et al. Circulation. 2007;116:e33-e38 7

 Reperfusion and Target Goal
I IIa IIb III
Reperfusion therapy should be administered to all eligible patients
with STEMI with symptom onset within the prior 12 hours.

I IIa IIb III

Primary PCI is the recommended method of reperfusion when it
can be performed in a timely fashion by experienced operators.

I IIa IIb III

In the absence of contraindications, fibrinolytic therapy should be
administered to patients with STEMI at non–PCI-capable hospitals
when the anticipated FMC-to-device time at a PCI-capable hospital
exceeds 120 minutes because of unavoidable delays.

I IIa IIb III

Reperfusion therapy is reasonable for patients with STEMI and
symptom onset within the prior 12 to 24 hours who have clinical
and/or ECG evidence of ongoing ischemia. Primary PCI is the
preferred strategy in this population.
O’Gara PT et al. Circulation. 2013;127:e362-e425
8
 Case
Mr M , 45 yo, come to remote non PCI capable hospital
complaining tightness of the chest 1hour prior to admission,
when watching TV radiated to the left arm for more than 20
min., History of chest pain precipitated by walking for 100 meter
relieved by taking rest. Cold sweating (+), nausea(+).
Risk factor : Smoking, Family history

BP: 150/70 mmHg, HR 94x/min, sat 96 % Temp 36

Normal JVP, no anemi, no icteric
C: within normal limit
P: Rh -/- wh -/-
Warm Acral
 ECG I

Dx: Inferior STEMI

 Management
• O2 2 l/m
• Nacl 1000 cc/24 jam
• DAPT (Ticagrelor 2 tablets and chewed aspilet
4 tablets)
• Atorvastatin 40 mg
• Refused PPI, fibrinolytic (streptrokinase)
therapy followed by SC enoxaparin 2.5 1 x1
ECG II
STEMI Guideline
STEMI Guideline
 NSTEACS Treatment Strategy

Adapted from : Roffi M et al. Eur Heart J 2016;37(3):267-315

 Risk Stratification
HIGH RISK VERY HIGH RISK
• Relevant rise or fall in troponin
• Dynamic ST- or T-wave changes • Haemodynamic instability or cardiogenic
(symptomatic or silent) shock
• GRACE Score > 140 • Recurrent or ongoing chest pain
refractory to medical treatment
• Life-threatening arrhythmias or cardiac
INTERMEDIETE RISK arrest
• Diabetes mellitus • Mechanical complications of MI
• Renal insufficiency • Acute heart failure
(eGFR <60 mL/min/1.73 m²) • Recurrent dynamic ST-T wave changes,
• LVEF < 40% or congestive HF particularly with intermittent ST-
• Early post infarction angina elevation
• Prior PCI LOW RISK
• Prior CABG
• Any characteristics not mentioned above
• GRACE risk score 109 - 140

Roffi M et al. Eur Heart J 2016;37(3):267-315

 Risk category GRACE In-hospital
(tertile) Risk Score death
(%)
Low ≤ 108 <1
Intermediate 109 - 140 1-3
High > 140 >3
Khalill R et al. Exp Clin Cardiol.2009; 14(2): e25 – e30
 Initial Treatment
Checklist of treatments when an ACS diagnosis
Initial therapeutic measures appears likely
Oxygen Aspirin
Insufflation (4–8 L/min) if oxygen Initial dose of 150–300 mg non-enteric formulation
saturation is <90% followed by 75–100 mg/day
Nitrates P2Y12 inhibitor
Sublingual or intravenous (caution Loading dose of ticagrelor or clopidogrel
if systolic blood
Anticoagulation
pressure is <90 mmHg)
Morphine Choice between different options depends on
strategy:
3–5 mg intravenous or • Fondaparinux 2.5 mg/daily sc
subcutaneously, if severe pain • Enoxaparin 1 mg/kg twice daily sc
• UFH i.v. bolus 60–70 IU/kg (maximum 5000 IU)
followed by infusion of 12–15 IU/kg/h
(maximum 1000 IU/h) titrated to aPTT 1.5–2.5 × control
Oral ß-Blocker
If tachycardic or hypertensive without signs of heart failure
Roffi M et al. Eur Heart J 2016;37(3):267-315; Hamm CW et al. Eur Heart J 2011;32:2999 – 3054
 Evolution of ACS Therapies
IIb/IIIa receptor CLOPIDOGREL
Low molecular antagonist Atorvastatin
weight heparin
Fondaparinux

Aspirin Bivalirudin

Heparin
Integrated
strategy
Early invasive management

1990 1996 1997 2000 2001 2005 2007 2008

Year

Adapted from White HD et al. Lancet 2008; 372: 570–84

 Case
Mr S. 51 yo.
Chief complain : Chest pain
Progressive typical angina since 3 days and worsen within 5 hour prior
to admission occur at mild activity. It did not relieved by resting.
History of STEMI 20 days before and refused PCI because of financial
problem with regular treatment of aspilet, clopidogrel, atorvastatin,
ramipril, bisoprolol and nitrate

BP: 139/95 mmHg, HR 86x/min, sat 96 % Temp 36

Normal JVP, no anemi, no icteric
C: within normal limit
P: Rh -/- wh -/-
Warm Acral
ECG I
 ECG II

No ECG change: NSTEACS

 Diagnosis and Planning

• Trop I : 16 at 12 h onset
• Clinical : Recurrent chest pain in recent onset
STEMI on treatment
• Echo : EF 36%
• Intermediate Risk NSTEMI  invasive Strategy
< 72 hr
 Risk category GRACE In-hospital
(tertile) Risk Score death
(%)
Low ≤ 108 <1
Intermediate 109 - 140 1-3
High > 140 >3
Khalill R et al. Exp Clin Cardiol.2009; 14(2): e25 – e30
 Management
• Loading DAPT
• Fondaparinux 2.5 mg/daily sc
• Statin
• Nitrate
• Ace-I
• Beta blocker
• PCI at 2nd day: LAD critical 95% long lesion at
LAD treated with 2 DES (heparin IV before DES
implantation) - chest pain free
Tight LAD Long lesion of Coronary Artery

Pre PCI Post PCI (2DES)

 NSTEACS Guideline

RoffiM, PatronoC EurHeart J.2015 Aug 29. pii: ehv320.41

 Recommendations for anticoagulants

RoffiM, PatronoC EurHeart J.2015 Aug 29. pii: ehv320.41

 Recommendations for anticoagulants

RoffiM, PatronoC EurHeart J.2015 Aug 29. pii: ehv320.41

 Recommendations for anticoagulants

RoffiM, PatronoC EurHeart J.2015 Aug 29. pii: ehv320.41

 Recommendations for anticoagulants

RoffiM, PatronoC EurHeart J.2015 Aug 29. pii: ehv320.41

 Recommendations for anticoagulants

RoffiM, PatronoC EurHeart J.2015 Aug 29. pii: ehv320.41

 Sites of Antithrombotic Drug Action
Tissue factor Collagen
Aspirin
Plasma clotting ADP
cascade
Fondaparinux Clopidogrel
Thromboxane A2 Prasugrel
AT
Prothrombin Cangrelor
Heparin AT Factor Platelet activation
LMWHs Xa Eptifibatide
AT
Abciximab
Thrombin Platelet aggregation Tirofiban
Bivalirudin (GPI)
Hirudin
Argatroban Fibrinogen Fibrin

Fibrinolytics Thrombus
Selective Factor Xa Inhibitor in
Management of ACS
A comparison of relevant pharmacological properties of the
different anticoagulant in current clinical use
UFH LMWH Arixtra
Presence of cofactor required +++ +++ +++
Renal clearance of clinical relevance ± ++ +
Non-specific protein binding +++ + +
Bioavailability by s.c or oral administration + ++ +++
( for s.c administration )

Predictability of pharmacological effect - ++ ++

Inhibition of thrombin generation ++ ++ ++
Inhibition of thrombin activity +++ + -
Inhibition of bound – thrombin - - -
Rebound of thrombin generation after discontinuation +++ ++ -

Platelet Activation +++ + -

Immune thrombocytopenia +++ + -
Decreased bone density +++ + -

Raffaele D.C, et al. Anticoagulants in Heart Disease : Current Status and Perspectives. Eur Heart J 2007 ; 28 : 880-913
 Fondaparinux
Fondaparinux is a Synthetic and Selective Xa Inhibitor
Fondaparinux Sodium, 2.5 mg/0.5 ml solution for injection,
in pre-filled syringe.

Fondaparinux 2,5 mg does not have clinically relevant affect on

routine coagulations test.

Unlike heparins or LMWH, fondaparinux is a synthetic compound and not derived from animal
products.

has rapid onset of action, 100% bioavailability after SC injection.

Elimination Half life is about 17 hours in healthy young subject and

about 21 hours in health elderly subject

eliminated mainly by the kidneys, and is contraindicated if CrCl is <20 mL/min

Reff :
1. ArixtraTM PI BPOM 4 October 2010, GDS04/IPI04 (23 January 2007).
2. Jack Hirsh MD, Fondaparinux 2007. Preface
 Fondaparinux
A Synthetic Inhibitor of Factor Xa

 Single chemical entity  No liver metabolism

 No risk of pathogen contamination  Does not bind significantly to plasma
 Highly selective for its target proteins other than AT.
 Once-daily administration  No reported cases of HIT
 Rapid onset (Cmax/2=25 min)  No dose adjustment necessary
in the healty elderly subject.
1.Herbert et al. A Noval Anti-factor Xa antitrombotic Agent . Cardiovasc Drug Rev 1997;15:1-26
2. Van Boeckel et al. The unique antithrombin III binding domain of Heparin: a lead to new Synthetic Antitrombotic. Angew
Chem [Int Ed Engl] 1993;32: 1671-90
3. ArixtraTM PI BPOM 4 October 2010, GDS04/IPI04 (23 January 2007).
 Fondaparinux
Mechanism of Action
Intrinsic Extrinsic
pathway pathway
Antithrombin

AT AT Xa Xa

Fondaparinux Pro-thrombin Thrombin

Reutilized
Fibrinogen Fibrin clot
1. Olson et al. Role of the antithrombin-binding Pentasaccharide in heparin acceleration of antithrombin-proteinase reaction
J Biol Chem 1992;267:12528-38
2. Turpie et al. A synthetic Pentasaccharide for the Prevention of deep-vein trombosis after total hip replacement.
N Engl J Med 2001;344:619-25
 Fondaparinux Indications

Treatment of ACS Prevention of VTE After Prevention of VTE in

MOS & Abdominal Surgery Medical Patients

 Treatment of UA/NSTEMI.  Hip Fracture.  Congestive Heart Failure.

 Acute Respiratory Illness.
 Adjuctive Treatment STEMI.  Knee Replacement Surgery.  Acute Infection Inflammatory
diseases
 Hip Replacement Surgery.

Abdominal Surgery.

1. ArixtraTM PI BPOM 4 October 2010, GDS04/IPI04 (23 January 2007).

2. Salim Yusuf, et al. Comparison of Fondaparinux and Enoxaprine in Acute Coronary Syndrome.
The fifth organization to assess strategies in Acute Ischemic Syndrome investigator. N Egl J Med 2006:354:1446-76
3. Salim Yusuf. Et al. The OASIS 6 trial. Effect of Fondaparinux on Mortality and Reinfarction in Patients with Acute ST-segment elevation MI.
Jama 2006; 259:1519-30.
4. Turpei Agg, et al. Fondaparinux vs Enoxaparine for the prevention of VTE in MOS.
A meta-analysis of randomized double blind studies. Arch Intern Med 2002;162:1883-40.
5. Cohen AT, et al : Efficacy and Safety Fondaparinux for The Prevention of VTE in older medical patients,
BMJ 2006: 332: 325-9
6. AgnelliG et al. Randomized Clinical Trial of post operative fondaparinux versus perioperative daltaparine of venous
thromboembolism in high risk abdominal surgery. Br J Surg 2005;92:1212-20.
 Fondaparinux Study
Treatment of ACS Prevention of VTE After Prevention of VTE in
MOS & Abdominal Surgery Medical Patients

 OASIS 5 Study : 20,000  MOS Meta Analysis Study :  Artemis Study : 890
patients with UA/NSTEMI. 7,344 patients. Acutely ill medical
a) EPHESUS : Elective Hip Surgery patients.
 OASIS 6 Study : 12,000 : 2309 patients
patients with STEMI. b) PENTHATHLON : Total hip
Surgery: 2275 patients
c) PENTAMAKS : Major Knee
Surgery : 1,049 Patiets.
d) PENTHIFRA : Hip Fracture
Surgery : 1,711 Patiets.
 PEGASUS Study : 2,048 patient
untder going Major Abdominal
Surgery

1. ArixtraTM PI BPOM 4 October 2010, GDS04/IPI04 (23 January 2007).

2. Salim Yusuf, et al. Comparison of Fondaparinux and Enoxaprine in Acute Coronary Syndrome.
The fifth organization to assess strategies in Acute Ischemic Syndrome investigator. N Egl J Med 2006:354:1446-76
3. Salim Yusuf. et al. The OASIS 6 trial. Effect of Fondaparinux on Mortality and Reinfarction in Patients with Acute ST-segment elevation MI.
Jama 2006; 259:1519-30.
4. Turpei Agg, et al. Fondaparinux vs Enoxaparine for the prevention of VTE in MOS.
A meta-analysis of randomized double blind studies. Arch Intern Med 2002;162:1883-40.
5. Cohen AT, et al : Efficacy and Safety Fondaparinux for The Prevention of VTE in older medical patients,
BMJ 2006: 332: 325-9
 Study Hypothesis OASIS 5

Fondaparinux 2.5 mg s.c. once daily

will show similar efficacy
to enoxaparin,
while improving bleeding

1. Michelangelo OASIS 5 Steering Committee. Am Heart J 2005;150:1107.e1-.e10

2. OASIS 5 Investigators. N Engl J Med 2006;354:1464-76
 OASIS 5: An International, Multicenter,
Randomized, Double-Blind, Double-Dummy
Trial in 41 Countries
20,078 patients with UA/NSTEMI

Aspirin, Clopidogrel, anti-GPIIb/IIIa,

planned Cath/PCI as per local practice

Randomization

Fondaparinux Enoxaparin
2.5 mg s.c. od up to 8 days 1 mg/kg s.c. bid for 2-8 days
1 mg/kg s.c. od if ClCr<30mL/min

Vital status ascertained in 20,066 (99.9%)

Lost to follow-up at day 9: fondaparinux: n=7 and enoxaparin: n=5

1. ArixtraTM PI BPOM 4 October 2010, GDS04/IPI04 (23 January 2007).

2. Salim Yusuf, et al. Comparison of Fondaparinux and Enoxaprine in Acute Coronary Syndrome.
The fifth organization to assess strategies in Acute Ischemic Syndrome investigator. N Egl J Med 2006:354:1446-76.
 Study Objectives and Outcomes
Objectives
Primary efficacy objective: To demonstrate non-inferiority of fondaparinux
compared with enoxaparin
Primary safety objective: To determine whether fondaparinux was
superior to enoxaparin in preventing major
bleeding

Outcomes (centrally adjudicated)

Primary efficacy: 1st occurrence of the composite of death, MI, or refractory
ischemia (RI) up to day 9
Primary safety: Major bleeding up to day 9
Risk benefit: Death, MI, refractory ischemia, major bleeds up to day 9
Secondary: Above & each component separately at days 30 and 180

1. ArixtraTM PI BPOM 4 October 2010, GDS04/IPI04 (23 January 2007).

2. Salim Yusuf, et al. Comparison of Fondaparinux and Enoxaprine in Acute Coronary Syndrome.
The fifth organization to assess strategies in Acute Ischemic Syndrome investigator. N Egl J Med 2006:354:1446-76.
 Fondaparinux has the same efficacy vs Enoxaparin
at Day 9 (Primary Efficacy: death/MI/RI)
Time to event death/MI/RI up to day 9
0.06

0.05

Cumulative Hazard
0.04
Enoxaparin
0.03
Fondaparinux
0.02
HR: 1.01
0.01
95% CI: 0.90-1.13
p=0.007 for non-inferiority
0.0

0 1 2 3 4 5 6 7 8 9
Days
Fondaparinux: 5.8% (579 events) Enoxaparin: 5.7% (573 events)

1. ArixtraTM PI BPOM 4 October 2010, GDS04/IPI04 (23 January 2007).

2. Salim Yusuf, et al. Comparison of Fondaparinux and Enoxaprine in Acute Coronary Syndrome.
The fifth organization to assess strategies in Acute Ischemic Syndrome investigator. N Egl J Med 2006:354:1446-76.
 Fondaparinux Significanly reduced Major Bleeding
vs Enoxaparin at day 9

0.04 Enoxaparin
HR: 0.52
95% CI: 0.44-0.61 p<0.001 48 %
0.03
Cumulative Hazard

0.02

Fondaparinux
0.01

0.0

0 1 2 3 4 5 6 7 8 9
Days

1. ArixtraTM PI BPOM 4 October 2010, GDS04/IPI04 (23 January 2007).

2. Salim Yusuf, et al. Comparison of Fondaparinux and Enoxaprine in Acute Coronary Syndrome.
The fifth organization to assess strategies in Acute Ischemic Syndrome investigator. N Egl J Med 2006:354:1446-76.
 Fondaparinux Significantly Reduced Mortality vs.
Enoxaparin up to Day 30
0.04

Enoxaparin
17 %
Cumulative Hazard 0.03

Fondaparinux
0.02

0.01
HR: 0.83
95% CI: 0.71-0.97
p=0.02
0.0

0 3 6 9 12 15 18 21 24 27 30
Days
1. ArixtraTM PI BPOM 4 October 2010, GDS04/IPI04 (23 January 2007).
2. Salim Yusuf, et al. Comparison of Fondaparinux and Enoxaprine in Acute Coronary Syndrome.
The fifth organization to assess strategies in Acute Ischemic Syndrome investigator. N Egl J Med 2006:354:1446-76.
 Fondaparinux Reduced the Rate of the Composite
of Death, MI or Stroke up to 6 Months
0.14
11 %
0.12 Enoxaparin

Cumulative Hazard 0.10 Fondaparinux

0.08

0.06

0.04
HR: 0.89
0.02 95% CI: 0.82-0.97
p=0.007
0.0
0 20 40 60 80 100 120 140 160 180
Days
1. ArixtraTM PI BPOM 4 October 2010, GDS04/IPI04 (23 January 2007).
2. Salim Yusuf, et al. Comparison of Fondaparinux and Enoxaprine in Acute Coronary Syndrome.
The fifth organization to assess strategies in Acute Ischemic Syndrome investigator. N Egl J Med 2006:354:1446-76.
 Major Bleeding Lower with Fondaparinux Irrespective
of Renal Function

0.10
Enoxaparin
(dose adjusted for renal function)
0.08
Fondaparinux
Major Bleed
0.06
0.04
0.02

40 60 80 100 120 140

GFR mL/min/1.73 m2
Fox KAA. Ann Int Med 2007;147:304-310
 Recommendations for Anticoagulants in Patients
with Normal and Impaired Renal Function

RoffiM, PatronoC EurHeart J.2015 Aug 29. pii: ehv320.41

12,092 Pasien
Study Hypothesis OASIS 6

Fondaparinux 2.5 mg s.c. once daily

will show superior efficacy
compared with usual care
 An International, Multicenter, Randomized, Double-
Blind, Double-Dummy Trial in 41 Countries

12,092 patients with STEMI

<12 h of symptom onset

Randomization

Fondaparinux Standard Care

1. ArixtraTM PI BPOM 4 October 2010, GDS04/IPI04 (23 January 2007).

2. Salim yusuf, et al. The OASIS 6 trial. Effect of Fondaparinux on Mortality and Reinfarction in Patients with Acute ST-segment elevation MI.
Jama 2006; 259:1519-30.
 12,092 patients with STEMI

Thrombolytics (SK, TPA, TNK, RPA),

Primary PCI or no reperfusion

Stratum 1 Stratum 2
UFH not indicated Randomization UFH Indicated

Fondaparinux s.c. Placebo Fondaparinux s.c. UFH i.v.

2.5 mg od/8 days* 8 days* 2.5 mg od/8 days* 24-48 h

• Vital status known at hospital discharge in 12,085 (99.9%)

• Follow-up: Day 30=12,072 (99.8%) – Study end=12,052 (99.7%)

1. ArixtraTM PI BPOM 4 October 2010, GDS04/IPI04 (23 January 2007).

2. Salim Yusuf , et alThe OASIS 6 trial. Effect of Fondaparinux on Mortality and Reinfarction in Patients with Acute ST-segment elevation MI.
Jama 2006; 259:1519-30.
 Study Objectives

Primary efficacy objective

To evaluate whether fondaparinux was superior to usual care (UFH or
placebo) in preventing death or recurrent MI in patients with STEMI

Primary safety objective

To evaluate the safety of fondaparinux compared with usual care, in
terms of severe bleeding, in patients with STEMI

1. ArixtraTM PI BPOM 4 October 2010, GDS04/IPI04 (23 January 2007).

2. Salim yusuf. Et al. The OASIS 6 trial. Effect of Fondaparinux on Mortality and Reinfarction in Patients with Acute ST-segment elevation MI.
Jama 2006; 259:1519-30.
 Fondaparinux Significantly Reduced the Rate
of Death/Reinfarction up to Day 30
0.16

0.14
UFH or placebo
Cumulative Hazard

0.12

0.10
Fondaparinux
0.08

0.06

0.04
HR: 0.86
0.02 95% CI: 0.77-0.96
p=0.008
0
0 3 6 9 12 15 18 21 24 27 30
Days
1. ArixtraTM PI BPOM 4 October 2010, GDS04/IPI04 (23 January 2007).
2. Salim Yusuf. Et al.The OASIS 6 trial. Effect of Fondaparinux on Mortality and Reinfarction in Patients with Acute ST-segment elevation MI.
Jama 2006; 259:1519-30.
 The Benefit of Fondaparinux Appeared at Day 9

9-day outcomes Fondaparinux Placebo/UFH HR 95%CI p value

n=6056 n=6036

Death/Reinfarction 7.4% 8.9% 0.83 0.73-0.94 0.003

Death 6.1% 7.0% 0.87 0.75-1.00 0.043

Reinfarction 1.6% 2.3% 0.67 0.52-0.88 0.004

Hazard Ratio (log scale)

0.1 1.0 10
Fondaparinux better Placebo/UFH better

1. ArixtraTM PI BPOM 4 October 2010, GDS04/IPI04 (23 January 2007).

2. Salim yusuf, et al . The OASIS 6 trial. Effect of Fondaparinux on Mortality and Reinfarction in Patients with Acute ST-segment elevation MI.
Jama 2006; 259:1519-30.
 There Was No Increased Risk of 30-Day Severe
Bleeding in Fondaparinux Group
0.016 UFH or placebo

Cumulative Hazard 0.014

0.012
Fondaparinux
0.010

0.008

0.006

0.004
HR: 0.79
0.002 (95% CI: 0.58-1.09)
p=0.15
0
0 3 6 9 12 15 18 21 24 27 30
Fondaparinux: 1.0% (61 events) Days
UFH or placebo: 1.3% (79 events)
1. ArixtraTM PI BPOM 4 October 2010, GDS04/IPI04 (23 January 2007).
2. Salim yusuf., et al The OASIS 6 trial. Effect of Fondaparinux on Mortality and Reinfarction in Patients with Acute ST-segment elevation MI.
Jama 2006; 259:1519-30.
 Fondaparinux Contraindications

Hypersensitivity to Active Clinically

Arixtra Bleeding

Acute Bacterial
Endocarditis CC < 20 ml/min

ArixtraTM PI BPOM 4 October 2010, GDS04/IPI04 (23 January 2007).

 Treatment of Bleeding

Discontinuation and
search for the primary Surgical Haemostasis.
cause

Fresh plasma
Blood replacements
transfusion.

ArixtraTM PI BPOM 4 October 2010, GDS04/IPI04 (23 January 2007).

 Summary
 In STEACS management  Primary PCI is preferred over Fibrinolytic, in
STEACS < 3 hr onset Fibrinolytic followed by fondaparinux is
recommended
 In NSTEACS risk stratification is need to identify the right time for
invasive strategy and referred to PCI hospital
 Fondaparinux 2.5 mg SC once daily is recommended by ESC guideline
for UA/NSTEMI patients as having favorable efficacy-safety (Class I)
 Based on OASIS 5, Fondaparinux (Arixtra®) is a selective factor Xa
inhibitor which offers good efficacy with less bleeding risk compared
to enoxaparin for management UA/NSTEMI
 Fondaparinux can be used for low to moderate renal impairment and
it’s contraindicated for severe renal impairment with CrCl < 20 ml/min
THANK YOU