Clopidogrel After MI Reduces Mortality and Major Vascular Events

NEW YORK (Reuters Health) -
Concomitant therapy with aspirin and clopidogrel improves survival and reduces the risk of stroke and reinfarction following MI, according to results of the ClOpidogrel and Metoprolol in Myocardial Infarction Trial (COMMIT), reported in the November 5th issue of The Lancet. And while the beta-blocker metoprolol decreases the risk of reinfarction and ventricular fibrillation after MI, it also increases the risk of cardiogenic shock during the first day or two. Therefore, "it may generally be prudent to start beta-blocker therapy after a patient's hemodynamic condition has stabilized after MI, with the aim of preventing reinfarction and sudden cardiac death during the later period of the hospital stay," co-author Dr. Zhengming Chen and his associates advise. The COMMIT trial included 45,852 patients admitted to 1250 hospitals within 24 hours of suspected acute MI onset. Subjects were randomly assigned to clopidogrel 75 mg or placebo, and metoprolol (15 mg IV loading dose then 200 mg oral daily) or placebo in a 2 x 2 factorial design. Patients were also treated with aspirin 162 mg daily. Outcomes were documented until hospital discharge or day 28. Clopidogrel reduced the co-primary composite outcome of death, reinfarction, or stroke by 9% (9.2% versus 10.1%, p = 0.002). The antiplatelet drug also reduced mortality by 7% (7.5% versus 8.1%, p = 0.03). Clopidogrel was not associated with cardiogenic shock, heart failure, presumed cardiac rupture, ventricular fibrillation, other cardiac arrest, pulmonary embolus, or major bleeds. Its effect was unrelated to patient age, use of fibrinolytic therapy or metoprolol. However, clopidogrel appeared to be more effective the earlier it was started after onset of symptoms (16% reduction in composite endpoint when given < 6 hours after symptom onset, 10% for 6 to 13 hours, and -1% for 13 hours to 24 hours). Given its fairly low cost, no need for careful monitoring, definite benefits and lack of hazards, the authors conclude, "clopidogrel (probably starting with a loading dose) should be considered for almost all patients presenting in hospital with suspected acute MI, irrespective of their age, sex, and the use of other treatments (provided that there are no strong contraindications)." For the metoprolol analysis, the investigators observed no significant differences in the composite of death, reinfarction, or cardiac arrest, or in death from any cause. But when they evaluated the causes of death separately, allocation to metoprolol was associated with a 22% proportional reduction in death from arrhythmia (p = 0.002), and a 29% increase in death due to cardiogenic shock (p = 0.002). They also observed an 18% reduction in risk of reinfarction (p = 0.001), a 17% reduction in risk of ventricular fibrillation (p = 0.001), and a 12% increase in heart failure requiring treatment (p < 0.0001). Dr. Chen's group points out that the balance of hazards and benefits of early metoprolol therapy correlated strongly with the background risk of shock. "The overall net effect of metoprolol therapy on the combined efficacy and safety outcome changed from being significantly adverse during days 0 to 1 to being significantly beneficial thereafter," they add. The findings of the COMMIT collaborative group "show the value in STEMI of routinely administering clopidogrel as part of the initial pharmacological reperfusion regimen and starting beta blockers once it is hemodynamically prudent to do so," Dr. Marc S. Sabatine, from Harvard Medical School in Boston, comments in a related editorial.
Lancet 2005;366:1587-1589,1607-1616,1622-1632.
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