Dose Comparisons of Clopidogrel and Aspirin in Acute Coronary Syndromes


Background: Clopidogrel and aspirin are widely used for patients with acute coronary syndromes and those undergoing percutaneous coronary intervention (PCI). However, evidence-based guidelines for dosing have not been established for either agent.


Methods: We randomly assigned, in a 2-by-2 factorial design, 25,086 patients with an acute coronary syndrome who were referred for an invasive strategy to either

• double-dose clopidogrel (a 600-mg loading dose on day 1, followed by 150 mg daily for 6 days and 75 mg daily thereafter) or
• standard-dose clopidogrel (a 300-mg loading dose and 75 mg daily thereafter) and either higher-dose aspirin (300 to 325 mg daily) or lower-dose aspirin (75 to 100 mg daily)
  

The primary outcome was cardiovascular death, myocardial infarction, or stroke at 30 days.


Results:

• The primary outcome occurred in 4.2% of patients assigned to double-dose clopidogrel as compared with 4.4% assigned to standard-dose clopidogrel
  Major bleeding occurred in 2.5% of patients in the double-dose group and in 2.0% in the standard-dose group
• Double-dose clopidogrel was associated with a significant reduction in the secondary outcome of stent thrombosis among the 17,263 patients who underwent PCI
• There was no significant difference between higher-dose and lower-dose aspirin with respect to the primary outcome or major bleeding
  

Conclusions: In patients with an acute coronary syndrome who were referred for an invasive strategy, there was no significant difference between a 7-day, double-dose clopidogrel regimen and the standard-dose regimen, or between higher-dose aspirin and lower-dose aspirin, with respect to the primary outcome of cardiovascular death, myocardial infarction, or stroke.

Dose Comparisons of Clopidogrel and Aspirin in Acute Coronary Syndromes - N Engl J Med 2010; 363:930-942 September 2, 2010