"Clopidogrel in Patients with Acute Coronary Syndromes". The New England Journal of Medicine. 2001. 345(7):494-502. PubMed • Full text • PDF
Contents
1 Clinical Question
2 Bottom Line
3 Major Points
4 Guidelines
5 Design
6 Population
6.1 Inclusion Criteria
6.2 Exclusion Criteria
6.3 Baseline Characteristics
7 Interventions
8 Outcomes
8.1 Primary Outcomes
8.2 Secondary Outcomes
9 Safety
10 Subgroup Analyses
11 Further Reading
Clinical Question
In patients with acute coronary syndromes without ST-segment elevation, does the addition of clopidogrel to aspirin reduce the risk of cardiovascular events?
Bottom Line
In patients with acute coronary syndromes without ST-segment elevation, treatment with clopidogrel plus aspirin reduced the risk of cardiovascular death, myocardial infarction, or stroke compared with aspirin alone but increased the risk of major bleeding.
Major Points
Guidelines
Guidelines recommend dual antiplatelet therapy with clopidogrel and aspirin for patients with acute coronary syndrome without ST-segment elevation, particularly in those not undergoing revascularization procedures.
Design
- Multicenter, double-blind, placebo-controlled trial
- N=12,562
- Clopidogrel + aspirin (n=6259)
- Placebo + aspirin (n=6303)
- Setting: 482 centers in 28 countries
- Enrollment: 1998-2000
- Mean follow-up: 9 months
- Analysis: Intention-to-treat
- Primary outcomes: Composite of death from cardiovascular causes, nonfatal MI, or stroke; and the composite of the first primary outcome or refractory ischemia
Population
Inclusion Criteria
- Hospitalized within 24 hours after the onset of symptoms
- No ST-segment elevation
Exclusion Criteria
- Contraindications to antiplatelet therapy
- High bleeding risk or severe heart failure
- Using oral anticoagulants
- Recent revascularization or glycoprotein IIb/IIIa receptor inhibitors
Baseline Characteristics
- Similar across the groups
Interventions
- Clopidogrel (300 mg loading dose, 75 mg daily) + aspirin (75 to 325 mg daily)
- Placebo + aspirin (75 to 325 mg daily)
Outcomes
Primary Outcomes
- First primary outcome: 9.3% in clopidogrel group vs. 11.4% in placebo group (RR 0.80; 95% CI, 0.72 to 0.90; P<0.001)
- Second primary outcome: 16.5% in clopidogrel group vs. 18.8% in placebo group (RR 0.86, P<0.001)
Secondary Outcomes
- In-hospital severe ischemia, recurrent angina, heart failure, and revascularization were also significantly lower with clopidogrel.
Safety
- Major bleeding: 3.7% in the clopidogrel group vs. 2.7% in the placebo group (RR 1.38; P=0.001)
- Life-threatening bleeding: no significant difference
Subgroup Analyses
- Consistent benefits across various subgroups (e.g., different doses of aspirin, use of other medications, prior revascularization)
Further Reading
- The original publication in NEJM