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Am Fam Physician. 2005;72(10):2111

Many patients receiving fibrinolytic treatment for myocardial infarction (MI) with ST-segment elevation experience failed reperfusion (20 percent) or reocclusion of the infarct-related artery (5 to 8 percent). These events are associated with increased risk of complications and increased mortality rates. Aspirin and clopidogrel (Plavix) have been proven to reduce these outcomes. Sabatine and colleagues evaluated the addition of clopidogrel to a standard fibrinolytic regimen, including aspirin, in patients with ST-segment elevation MI.

The authors enrolled 3,491 patients in 23 countries in a randomized, double-blind, placebo-controlled trial. The average age of participants was 57 years; 80 percent of the patients were men, and almost 90 percent were white. At enrollment, 89 percent of the patients were on beta-blocker therapy, 80 percent were taking statins, and 72 percent were taking an angiotensin-converting enzyme inhibitor or angiotensin-II receptor blocker.

Enrollment criteria included ischemic chest pain at rest for more than 20 minutes within 12 hours before randomization; ST-segment elevation in two limb or precordial leads or a new left bundle branch block; and administration of a fibrinolytic agent and aspirin. Patients who had coronary artery bypass graft surgery or plans to use a glycoprotein IIb/IIIa inhibitor before angiography were excluded from the study.

Participants were randomized to receive a 300-mg loading dose of clopidogrel (followed by a 75-mg dosage once daily) or placebo. Coronary angiography was performed 48 to 192 hours after medication administration. Patients who received coronary stents were recommended for open-label clopidogrel after angiography; 56.7 percent of the patients in the treatment group and 57.4 percent in the placebo group subsequently were given open-label clopidogrel or ticlopidine (Ticlid).

The primary endpoints were an occluded infarct-related artery on angiography, death from any cause before angiography, and recurrent MI before angiography. Patients were followed during hospitalization, and follow-up was performed 30 days afterward.

Patients in the clopidogrel group had an absolute reduction of 6.7 percent and a relative reduction of 36 percent in the combined primary endpoints. These findings were consistent across the study group. An occluded infarct-related artery was the only endpoint in which a significant change was noted in the treatment group. There was no effect on the specific endpoint of death, and the reduction in MI was 1.1 percent (P = .08). At 30 days, the treatment group had a significant reduction in recurrent MI (1.8 percent absolute reduction, 31 percent relative reduction) and in the combined outcomes of cardiovascular death, recurrent MI, stroke, or recurrent ischemia leading to intervention (2.5 percent absolute reduction, 20 percent relative reduction). When the combined outcomes were examined individually, the effect was no longer significant. There were no differences in the percentage of patients who underwent percutaneous intervention or coronary artery bypass graft surgery after treatment, and there was no increase in major or minor bleeding events in the clopidogrel group.

The authors conclude that adding clopidogrel to a standard fibrinolytic regimen with aspirin improves infarcted artery patency and reduces ischemic complications without an increase in bleeding complications.

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