About 10 million persons worldwide have acute myocardial infarction (MI) every year. Despite improvements in immediate care, the rates of mortality and morbidity remain high, prompting interest in simple early interventions that could reduce the effects of this condition. The COMMIT (ClOpidogrel and Metoprolol in Myocardial Infarction Trial) study focused on early administration of the antiplatelet drug clopidogrel (Plavix) plus aspirin in myocardial infarction.
The randomized, placebo-controlled trial recruited more than 45,000 Chinese patients presenting with S-T elevation or depression, or left bundle branch block within 24 hours of onset of acute symptoms of MI. Patients who had no contraindications to the study medications were randomly assigned to immediate treatment with 162 mg aspirin plus 75 mg clopidogrel or an identical placebo. Patients then received the same two pills every day for four weeks in addition to whatever therapy was deemed appropriate by the attending physicians. All additional antiplatelet therapy was avoided unless a strong indication developed for its use. Patients were reassessed at day 28 or on hospital discharge for occurrence of major clinical events, death and cause of death, compliance with study medications, possible adverse effects, and use of additional treatments. The primary outcomes measured were all-cause mortality and the composite of death, reinfarction, or stroke.
The 22,961 patients assigned to aspirin plus clopidogrel were comparable with the 22,891 assigned to aspirin plus placebo in all significant variables. The mean age was 61 years, and the mean time from symptom onset to treatment was 10 hours. Eight percent of participants had a previous MI, and 43 percent had hypertension. Before this event, 18 percent had used aspirin. One half of the study participants received fibrinolytic therapy before randomization. The mean duration of treatment was 14.9 days in both groups. The two groups did not differ significantly in participants’ reasons for discontinuing therapy.
Both primary outcomes showed significant reduction in the aspirin plus clopidogrel group. The 1,726 deaths (7.5 percent) in the clopidogrel group were significantly lower than the 1,845 deaths (8.1 percent) in the placebo group. For the combined outcome of death, reinfarction, and stroke, the 2,121 events (9.2 percent) in the clopidogrel group were significantly less than the 2,310 events (10.1 percent) in the control group. No differences were recorded between the groups in other major outcomes (i.e., heart failure, cardiogenic shock, presumed cardiac rupture, ventricular fibrillation, other cardiac arrest, pulmonary embolism). No significant differences occurred in the incidence of major bleeding complications (0.58 percent for clopidogrel compared with 0.55 percent for placebo), but patients in the clopidogrel group had a small but significant increase in minor bleeding complications. The minor bleeding events were mainly oral and skin bleeding and amounted to an excess of 4.7 events per 1,000 patients. Overall, about two weeks of clopidogrel therapy was associated with a savings of nine events (death, reinfarction, or stroke) per 1,000 patients.
The authors conclude that clopidogrel should be considered for all cases of suspected acute MI if there are no contraindications. They argue that the savings over the longer term could be much greater.