- Question
- To determine whether a double-dose clopidogrel regimen and/or a higher aspirin dose improve outcomes compared with standard doses in patients with acute coronary syndrome managed with an invasive strategy.
- Design
- Multinational, randomized, double-blind trial with a 2-by-2 factorial design, enrolling 25086 patients with acute coronary syndrome referred for an invasive strategy.
- Population
- Patients with acute coronary syndrome (unstable angina or myocardial infarction) referred for an early invasive strategy, including those who subsequently underwent percutaneous coronary intervention (PCI).
- Intervention
- Double-dose clopidogrel (600-mg loading dose on day 1, then 150 mg daily for 6 days and 75 mg daily thereafter) and/or higher-dose aspirin (300 to 325 mg daily).
- Control
- Standard-dose clopidogrel (300-mg loading dose, then 75 mg daily) and/or lower-dose aspirin (75 to 100 mg daily).
- Primary outcome
- Composite of cardiovascular death, myocardial infarction, or stroke at 30 days.
- Results
- The primary outcome occurred in 4.2% with double-dose clopidogrel vs. 4.4% with standard dose (HR 0.94; 95% CI 0.83 to 1.06; P=0.30). Among the 17263 patients who underwent PCI, stent thrombosis was lower with double dose (1.6% vs. 2.3%; HR 0.68; 95% CI 0.55 to 0.85; P=0.001). For aspirin, there was no difference in the primary outcome between higher and lower dose (4.2% vs. 4.4%; HR 0.97; 95% CI 0.86 to 1.09; P=0.61).
- Safety
- Major bleeding was more frequent with double-dose clopidogrel (2.5% vs. 2.0%; HR 1.24; 95% CI 1.05 to 1.46; P=0.01). For aspirin, there was no difference in major bleeding between higher and lower dose (2.3% vs. 2.3%; HR 0.99; 95% CI 0.84 to 1.17; P=0.90).
- Conclusion
- In patients with acute coronary syndrome managed with an invasive strategy, neither a 7-day double-dose clopidogrel regimen nor higher-dose aspirin significantly reduced the primary outcome compared with standard doses.
- Why it matters
- The trial informed dosing of clopidogrel and aspirin in acute coronary syndrome, showing that a higher aspirin dose offers no benefit and that double-dose clopidogrel is associated with more bleeding, with a possible limited benefit in the PCI population.
Card generated automatically with AI from the abstract of the original publication and the trial registry; every figure was checked against those sources. It may contain errors: verify the data at the source before using it for clinical decisions.
Generated on October 10, 2026