Professional Documents
Culture Documents
Objectives
Acute Coronary Syndromes Pharmacist:
(ACS) Distinguish between unstable angina (UA), non-ST
elevation myocardial infarction (NSTEMI) and ST-
segment elevation myocardial infarction (STEMI)
Review treatment modalities in ACS
Liane Horiuchi, Pharm.D.
PGY-1 Pharmacy Resident Describe different reperfusion therapies and their roles
Memorial Hospital Miramar Technician:
March 13, 2016
Define ACS and its associated risk factors
Review what drugs are used to treat ACS
Explain the significance of timely treatment of ACS
www.fshp.org 3
STEMI NSTEMI
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NSTE: Non-ST-Segment Elevation 7
Average age at first MI is 65 years for men and 71.8 years for
women.
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Heart Disease and Stroke Statistics 2015 Update. Circulation 2015. Finks SW. Acute Coronary Syndromes. ACCP Updates in Therapeutics 2015.
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Echocardiogram (ECG)
EMS & w/in 10 min at ED, then q15-30min if not initially diagnostic
ST-changes developing at rest strongly suggest acute ischemia:
Initial Management of NSTE-ACS ST = STEMI ST = NSTEMI = UA (?)
Inverted T waves may also indicate UA/NSTEMI
(UA/NSTEMI) Q waves suggesting prior MI indicate a high likelihood of CAD
ST elevation in posterior leads V7-V9 qualifies the patient for
reperfusion therapy as a STEMI
Normal ECG no NSTEMI or UA
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Amsterdam EA, et al. AHA/ACC guideline for the management NSTEMI ACS. Circulation 2014.
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PGY12 Antagonists
Parameter Clopidogrel Prasugrel Ticagrelor
FDA Indication ACS managed medically or PCI ACS PCI ACS managed medically or PCI
Peak Platelet LD: 300mg, ~6h, LD: 60mg, ~1-1.5h LD: 180mg, <1h
Inhibition 600mg, ~2h
Adverse Effects Bleeding, GI hemorrhage Bleeding, HTN, HLD, A.fib, Bleeding, Scr, dyspnea
bradyarrhythmia
Metabolism Prodrug; 2-step process Prodrug; converted to active Not prodrug; reversible
involving 2C19 and 3A4 metabolite via P450 pathways noncompetitive binding. 3A4
(primary), 3A5, Pgp
T1/2 8h metabolite 3.7h metabolite (2-15h range) 7h (parent), 9h(active metabolite)
22 Adapted from Finks SW. Acute Coronary Syndromes. ACCP Updates in Therapeutics 2015. 24
Lscher TF, et al. European Heart Journal. August 2011.
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Management of NSTE-ACS:
Anticoagulant Other Early Hospital Therapies
Loading Dose Maintenance Dose Comments COR LOE
Nitrates: Topical or Oral
Heparin 60 IU/kg IVB 12 IU/kg/hr (max1000IU/hr) aPTT goal: 50-75s I B ACE-Inhibitors:
over >1 min x 48h or until PCI performed CHF, EF<40%, HTN, DM, stable CKD (ARB if intolerant)
(Max 4000 IU)
Aldosterone antagonist:
Enoxaparin 30mg IVB 1mg/kg SQ Q12h x 24-48h Highest bleeding I A On ACE-I and -blocker with EF<40%, Sx HF or DM and if
(Lovenox) CrCl<30: Q24h risk of 4 agents CrCl>30 ml/min and K<5.0 mEq/L
Calcium Channel Blocker:
Fondaparinux 2.5mg SQ daily Best for those I B For ischemic symptoms when -blocker not successful, CI, or
(Arixtra) - CrCl<30: Avoid with high risk of intolerant
bleeds Statins: High-intensity
Bivalirudin 0.1mg/kg IVB 0.25mg/kg/hr IV Only in early I B Nonsteroidal anti-inflammatory drugs (NSAIDs):
(Angiomax) if planned invasive surgery invasive strategy (Except aspirin) Should not be initiated and should be discontinued
or hx of HIT during hospitalization
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AHA/ACC Guideline for the management NSTEMI ACS. Circulation 2014.
Management of NSTE-ACS:
GP IIb/IIIa inhibitor Immediate Invasive Strategy
Intermediate/High risk: GP IIb/IIIa inhibitor may be considered as part of initial tx in
early invasive strategy. <90 minutes from presentation
GP IIb/IIIa Loading Dose Maintenance Dose Comments COR LOE Refractory angina
inhibitor
S/sx of HF or new/worsening mitral regurgitation
Eptifibatide 180mcg/kg IVB 2mcg/kg/min IV Continue until IIb B
(Integrilin) over 1-2 min infusion x 12-72h discharge, CABG Hemodynamic/electrical instability
(Max 22.6 mg) (Max 15 mg/hr) initiation, or 72h Recurrent angina or ischemia despite intensive medication
CrCl<50: 1 mcg/kg/min CrCl<10mL/min
(Max 7.5 mg/hr) CI: dialysis pts treatment
Severe VT or VF
Tirofiban 25mcg/kg IVB 0.15mcg/kg/min for up IIb B
(Aggrastat) to 18h
Severe comorbidities
CrCl<60: 0.075
mcg/kg/min
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AHA/ACC Guideline for the management NSTEMI ACS. Circulation 2014.
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Percutaneous Coronary
Intervention (PCI)
Balloon angioplasty alone
Initial Management of STEMI
Balloon angioplasty with stents
Bare metal stents (BMS)
Drug-eluting stent (DES)
Anti-proliferative agents: Sacrolimus, Paclitaxel, Everolimus,
Zotarolimus
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http://www.ica.artguys.com/IMAGES/Percutaneous-Coronary-Intervention.jpg
Percutaneous Coronary
Intervention (PCI) Pharmacologic:
Fibrinolytic
Bold lines are preferred strategies.
DIDO= door-in-door-out
30 *Patients with cardiogenic shock or severe HF initially seen at non-PCI-capable hospital should be
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https://www.nghs.com/fullpanel/uploads/files/cardiac-cath-lab.jpg transferred for cardiac catheterization and revascularization as soon as possible, irrespective of time
delay from MI onset (I, B) ACCF/AHA Guideline for the Management of STEMI. 2013.
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Management of STEMI:
STEMI Management
DAPT with Primary PCI
Reperfusion therapy for all eligible patients with STEMI with
Loading Dose Maintenance Dose COR LOE
symptom onset 12 hrs
Reperfusion therapy options: Percutaneous Coronary Intervention Aspirin 162 325mg 81 -325mg daily I B (LD)
(PCI) or fibrinolytic therapy prior to procedure Indefinitely (I,A)
First line Primary PCI
PCI- capable hospital (90 min) vs. non-PCI capable hospital (120
min) P2Y12 Loading Dose Maintenance Dose COR LOE
inhibitors
Second line Fibrinolytic therapy
Clopidogrel 600mg 75mg daily I B
If time is > 120 min to get to PCI hospital
Prasugrel 60mg 10mg daily I B
Management of STEMI:
STEMI Management Anticoagulant with Primary PCI
Anticoagulant Loading Dose Follow-Up Dose COR LOE
Reperfusion therapy reasonable for patients with STEMI UFH
with symptom onset in prior 12-24 hours if: With GP IIb/IIIa antagonist 50- to 70-U/kg IVB to Supplemental doses to I C
planned achieve therapeutic ACT target ACT
Clinical and/or ECG evidence of ongoing ischemia
First line: Primary PCI With no GP IIb/IIIa 70- to 100-U/kg IVB to Supplemental doses to I C
antagonist planned: achieve therapeutic ACT target ACT
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ACCF/AHA Guideline for the Management of STEMI. 2013. 38 Adapted from ACCF/AHA Guideline for the Management of STEMI. 2013. 40
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therapy
Before PCI During PCI After PCI
2. Fibrinolytic 2. Fibrinolytic
therapy therapy
3. Fibrinolytic, 3. Fibrinolytic,
then PCI then PCI
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Adapted from Calil M, Perrin D. Acute Coronary Syndromes. Adapted from Calil M, Perrin D. Acute Coronary Syndromes.
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Before fibrinolytic: 2. Enoxaparin: As part of invasive strategy in stable* patients with PCI between IIa B
-ASA 162-325 mg LD -Age < 75y: 30 mg IV bolus, then 1 mg/kg SQ q12h
-Clopidogrel as only P2Y12 inhibitor 3-24h after successful fibrinolysis
-Age > 75y: no bolus; 0.75 mg/kg SQ q12h
Age 75 y: 300 mg LD
Age > 75: No LD, give 75 mg 3. Fondaparinux: *absence of low output, hypotension, persistent tachycardia, apparent shock, high-grade ventricular or sx supraventricular
With Fibrinolytic: 2.5 mg IV, then 2.5 mg SQ daily in 24h tachyarrhythmias, and spontaneous recurrent ischemia
1. UFH: 60 U/kg IV bolus, then 12 U/kg/hr
infusion adjusted for aPTT 1.5-2x control Duration for both: Up to 8 days, or until
(~50-70s for 48h or until revascularization) revascularization
45 ACCF/AHA Guideline for the Management of STEMI. 2013. 47
After Fibrinolytic: See dosing table
Adapted from Calil M, Perrin D. Acute Coronary Syndromes.
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References
Coronary Artery Bypass Graft (CABG)
1. Amsterdam EA, et al. 2014 AHA/ACC guideline for the management of patients with non-ST-
elevation acute coronary syndromes. Circulation. 2014.
2. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1e157.
Anti-thrombotic therapy: 3. Braunwald et al. J Am Coll Cardiol. 2000;36:970-1062.
4. Bruhl, SR. Acute Coronary Syndrome. Internal Medicine Didactics. July 2010.
Give aspirin before CABG surgery 5. Calil M, Perrin D. Acute Coronary Syndromes. Overview of ACCF/AHA Guidelines for Acute
Management of UA/Non-ST-Elevation Myocardial Infarction (NSTEMI) and ST-Elevation
Discontinue clopidogrel or ticagrelor 24h before on- Myocardial Infarction (STEMI).
pump CABG 6. Finks SW. Acute Coronary Syndromes. Cardiology I. ACCP Updates in Therapeutics 2015.
7. Lscher TF et al. ESC Guidelines for the management of acute coronary syndromes in patients
Discontinue short acting IV GP IIb/IIIa antagonists 2-4h presenting without persistent ST-segment elevation. European Heart Journal. August 2011.
8. OGara PT et al. ACCF/AHA Guideline for the Management of STEMI: A Report of the American
before urgent CABG College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J
Am Coll Cardio. 2013; 61(4):e78-e140.
Discontinue abciximab 12h before urgent CABG 9. Shapiro BP, Jaffe AS. Cardiac biomarkers. In: Murphy JG, Lloyd MA, editors. Mayo Clinic
Cardiology: Concise Textbook. 3rd ed. Rochester, MN: Mayo Clinic Scientific Press and New York:
Informa Healthcare USA, 2007:77380.
10. TIMI Calculator: Morrow DA. Circulation 2000. Antman EM. JAMA 2000.
11. https://www.thrombosisadviser.com/static/media/images/upload/anticoagulants-and-antiplatelets-
target.jpg
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