COMMIT (Clopidogrel and Metoprolol in Myocardial Infarction Trial)

Clopidogrel and Metoprolol in Myocardial Infarction Trial (COMMIT)

• this trial investigated the use of clopidogrel, in addition to aspirin, in patients with ST-elevation MI
  • study design
    • 45,852 patients admitted to 1250 hospitals within 24 h of suspected acute MI onset were randomly allocated clopidogrel 75 mg daily (n=22,961) or matching placebo (n=22,891) in addition to aspirin 162 mg daily
      • treatment was to continue until discharge or up to 4 weeks in hospital (mean 15 days in survivors) and 93% of patients completed it
      • the prespecified co-primary outcomes were:
        • (1) the composite of death, reinfarction, or stroke
        • (2) death from any cause during the scheduled treatment period
  • study results
    • allocation to clopidogrel produced a highly significant 9% (95% CI 3-14) proportional reduction in death, reinfarction, or stroke (2121 [9.2%] clopidogrel vs 2310 [10.1%] placebo; p=0.002), corresponding to nine (SE 3) fewer events per 1000 patients treated for about 2 weeks
    • also a significant 7% (1-13) proportional reduction in any death (1726 [7.5%] vs 1845 [8.1%]; p=0.03)
    • no significant excess risk was noted with clopidogrel, either overall (134 [0.58%] vs 125 [0.55%]; p=0.59), or in patients aged older than 70 years or in those given fibrinolytic therapy
  • conclusion
    • in patients hospitalised within 24 hours of suspected acute myocardial infarction, addition of clopidogrel to aspirin treatment (and other standard treatments) led to a reduction in risk of the composite end point of death, reinfarction, or stroke and did not increase the risk of major bleeding

Notes:

• the study also investigated the use of early intravenous and then oral metoprolol in this cohort of patients. Intravenous metoprolol did not reduce risk of the composite end point of death, reinfarction, or cardiac arrest. Use of intravenous metoprolol was associated with an increased risk of cardiogenic shock, particularly during the first few days after admission - however there was a reduction of risk of reinfarction and ventricular fibrillation

Reference:

1. COMMIT Collaborative Group. Addition of clopidogrel to aspirin in 45 852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet 2005;366:1607-21
2. COMMIT Collaborative Group. Early intravenous then oral metoprolol in 45 852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet 2005;366:1622-32.