Clopidogrel -- Early Mortality Benefit After STEMI

Clopidogrel — Early Mortality Benefit After STEMI

Insights from COMMIT

Dual antiplatelet therapy with aspirin and clopidogrel is standard care in patients undergoing percutaneous coronary intervention (PCI), and data from the CLARITY-TIMI 28 trial have shown that clopidogrel treatment enhances the likelihood that fibrinolytic therapy will yield a patent infarct-related artery after ST-segment-elevation MI (STEMI; Journal Watch Cardiology Apr 8 2005). Do clopidogrel’s post-STEMI benefits extend to improved outcomes?

In COMMIT, a double-blind trial cofunded by manufacturers of clopidogrel, researchers in China randomized 45,852 patients (mean age, 61) who presented within 24 hours of suspected STEMI onset (mean, 10 hours; 34% <6 hours) to daily regimens of either clopidogrel (75 mg; without a loading dose) plus aspirin (162 mg) or aspirin alone. About 54% of patients received fibrinolysis, mainly urokinase; only 3% underwent elective PCI. Mean treatment duration in survivors was 15 days. (The subjects were also separately randomized to early beta-blockade or placebo [see Journal Watch Cardiology Dec 16 2005].)

Compared with recipients of aspirin alone, dual-therapy recipients had significantly lower 30-day incidences of the primary composite endpoint of death, reinfarction, or stroke (9.2% vs. 10.1%) and of death alone (7.5% vs. 8.1%). A subgroup analysis revealed that the primary-endpoint benefit was restricted to fibrinolysis recipients. The incidence of major bleeding was similar in the two groups overall (about 0.6% in each), within the subset of patients age 70 or older, and within the subset of patients who received fibrinolytic therapy.

Comment: Adding clopidogrel (75 mg daily) to aspirin therapy prevented 9 cardiovascular events per 1000 STEMI patients treated and yielded a significant early mortality benefit, with no short-term safety disadvantage. Some caveats are (1) the chief fibrinolytic agent used in COMMIT (urokinase) is not available in the U.S. and is not fibrin-specific; (2) for elderly recipients of fibrinolytic therapy, safety data are available only in patients who did not receive a loading dose of clopidogrel; and (3) the trial had a relatively low rate of reperfusion therapy (54%). Even with these caveats, data from COMMIT and from CLARITY-TIMI 28 collectively suggest that clopidogrel can enhance the benefits of reperfusion therapy in a broad range of STEMI patients.

— Beat J. Meyer, MD

Published in Journal Watch Cardiology December 27, 2006

Citation(s):

COMMIT (ClOpidogrel and Metoprolol in Myocardial Infarction Trial) collaborative group. Addition of clopidogrel to aspirin in 45 852 patients with acute myocardial infarction: Randomised placebo-controlled trial. Lancet 2005 Nov 5; 366:1607-21.