Clopidogrel beneficial during acute phase of MI; metoprolol has no overall effect

Clopidogrel reduces 28-day mortality in the treatment of patients with acute myocardial infarction (MI) when given on top of standard therapies, but metoprolol has no effect on in-hospital mortality when given during the acute phase of MI.

These were the findings of COMMIT (Clopidogrel and Metoprolol in Myocardial Infarction Trial), a multicenter study of 45,852 patients with suspected acute MI treated within 24 hours of symptoms. Results of the trial were reported at the ACC Annual Scientific Session 2005.

Patients were randomized to clopidogrel 75 mg/d or placebo; all patients were treated with aspirin 162 mg/d. Patients were further randomized to receive three 5-mg IV doses of metoprolol, followed by either oral metoprolol 200 mg/d or placebo.

The advantage of clopidogrel with respect to the primary end point was already evident in the first 24 hours, he said. Subgroup analysis showed that patients presenting within the first 12 hours of symptom onset derived the most benefit from clopidogrel. The favorable effect was apparent whether or not fibrinolytics were used.

There was no excess of cerebral, fatal, or transfused bleeds in the clopidogrel-treated group, even when given with fibrinolytic therapy or in older recipients.

Adding clopidogrel to aspirin during the treatment of acute MI would prevent approximately 10 major vascular events per 1,000 patients treated, said Dr Chen.

Metoprolol, in contrast, did not significantly reduce in-hospital mortality or the incidence of the composite primary end point at a mean follow-up of 16 days, reported Rory Collins, MD. The primary end point of the metoprolol randomization of COMMIT was the composite of death, reinfarction, and cardiac arrest, which occurred in 9.5% of the metoprolol recipients and 9.9% of the placebo recipients. All-cause mortality was 7.7% and 7.8% in the metoprolol and placebo groups, respectively.

Compared with placebo, metoprolol reduced the absolute risk of reinfarction by 5 per 1,000 patients treated (P=.001) and of ventricular fibrillation by 6 per 1,000 (P<.001).

The increased risk of cardiogenic shock with metoprolol, however, offset the beneficial effects on reinfarction and ventricular fibrillation, said Dr Collins, a British Heart Foundation professor of medicine and epidemiology at the University of Oxford, United Kingdom.

Metoprolol increased the risk of cardiogenic shock by 11 cases per 1,000 (P<.00001). "Most of the excess in cardiogenic shock occurred during the first day in the hospital," Dr Collins said. The results indicate that beta blockade should be initiated only in stable patients, and then gradually, he said.