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Clopidogrel-Enhanced Fibrinolysis After STEMI

In relatively low-risk patients with ST-segment-elevation MI, clopidogrel increased the likelihood that fibrinolytic therapy (including aspirin) would yield a patent infarct-related artery.

Does adding clopidogrel to standard fibrinolytic therapy (including aspirin) benefit patients with ST-segment-elevation MI (STEMI)? In a double-blind trial funded by clopidogrel's manufacturer, researchers randomized 3491 adults (maximum age, 75; mean, 57; 80% men; 90% white) who presented with STEMI within 12 hours of symptom onset to clopidogrel (a 300-mg loading dose, then 75 mg once daily) or placebo, given an average of 10 minutes after fibrinolysis. Angiography was performed in 94% of patients a median of 84 hours after randomization. Only 4% of patients underwent bypass surgery.

The primary endpoint was an occluded infarct-related artery on angiography, or death or recurrent MI before angiography (or, for patients who did not undergo angiography, before day 8 or discharge, whichever came first). Incidence of this endpoint was significantly lower among clopidogrel recipients than among placebo recipients (15% vs. 22%), mostly due to a difference in infarct-related artery occlusion (12% vs. 18%). The two groups had similar rates of mortality (2.6% and 2.2%, respectively) and major bleeding (1.3% and 1.1%). Clopidogrel was associated with a significantly lower 30-day incidence of cardiovascular death, recurrent MI, or recurrent ischemia requiring urgent revascularization (11.6%, vs. 14.1% with placebo).

Comment: In this trial involving relatively low-risk STEMI patients, clopidogrel increased the likelihood that fibrinolytic therapy (including aspirin) would yield a patent infarct-related artery, without compromising safety. The cost of this short-term regimen is minimal, so the main caveat is that the trial relied on a surrogate outcome (artery patency) and not on true patient outcomes.

— Harlan M. Krumholz, MD, SM

Published in Journal Watch Cardiology April 8, 2005

Citation(s):

Sabatine MS et al. for the CLARITY-TIMI 28 Investigators. Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation. N Engl J Med 2005 Mar 24; 352:1179-89.

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Lange RA and Hillis LD. Concurrent antiplatelet and fibrinolytic therapy. N Engl J Med 2005 Mar 24; 352:1248-50.

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• Medline abstract (Free)