Clopidogrel Or Metoprolol in Myocardial Infarction Trial

Clopidogrel

Despite considerable improvements in the emergency treatment of acute myocardial infarction (MI), including the use of aspirin, early mortality and morbidity remain high. The antiplatelet agent clopidogrel adds to the benefit of aspirin in acute coronary syndromes without ST-segment elevation, but its effects on mortality and morbidity in patients with ST-elevation MI were unclear.

45,852 patients admitted to 1250 hospitals within 24 hours of the onset of suspected acute MI were randomly allocated to receive clopidogrel 75 mg daily or matching placebo (both in addition to aspirin 162 mg daily). 93% had ST-segment elevation or bundle branch block, and 7% had ST-segment depression. Treatment was to continue until discharge or up to a maximum of 4 weeks in hospital (mean 15 days in survivors), and 93% completed it. The two pre-specified co-primary outcomes were: (i) the composite of death, reinfarction or stroke; and (ii) death from any cause during the scheduled treatment period. Comparisons were between all clopidogrel-allocated and all placebo-allocated patients (ie, "intention-to-treat"), and used the log-rank method.

Allocation to clopidogrel produced a highly significant 9% (95% CI 3-14) proportional reduction in the primary composite outcome of death, reinfarction or stroke (2121 [9.2%] clopidogrel vs 2310 [10.1%] placebo; p=0.002), corresponding to 9 (SE 3) fewer events per 1000 patients treated for about 2 weeks. There was also a significant 7% (95% CI 1-13) proportional reduction in the co-primary outcome of any death (1726 [7.5%] vs 1845 [8.1%]; p=0.03). These effects on death, reinfarction and stroke appeared to be consistent across a wide range of patients and independent of other treatments being used. Considering all transfused, fatal or cerebral bleeds together, no significant excess risk was observed with clopidogrel, either overall (134 [0.58%] vs 125 [0.55%]; p=0.59), or among patients aged 70 years or older (50 [0.84%] vs 43 [0.72%]; p=0.48) or among those given fibrinolytic therapy (74 [0.65%] vs 72 [0.63%]; p=0.88).

In a wide range of patients with acute MI, adding clopidogrel 75 mg daily to aspirin and other standard treatments (such as fibrinolytic therapy) reduces mortality and major vascular events in hospital, without any material increase in major bleeding.