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More Data for the Post-MI Warfarin vs. Aspirin Debate

Is there a best antithrombotic approach to secondary prevention after myocardial infarction?

These researchers from Norway sought to clarify the relative efficacy of 3 antithrombotic regimens for secondary prevention after MI. They randomized 3630 survivors of MI (mean age, 60; maximum age, 74; mean LV ejection fraction, 52%) to warfarin (target INR, 2.8-4.2); aspirin (160 mg/day); or aspirin (75 mg/day) plus warfarin (target INR, 2.0-2.5). No patients had contraindications to the study drugs. The primary outcome was a composite of death, nonfatal reinfarction, or thromboembolic stroke.

By follow-up (mean, 4 years), 625 patients (17%) had at least 1 event. Compared with aspirin alone, aspirin plus warfarin was associated with a 29% lower risk for any event (P=0.001), warfarin alone with a 19% lower risk (P=0.03). The 3 groups had nearly identical death rates, but rates of reinfarction and thromboembolic stroke were significantly lower in the 2 warfarin groups than in the aspirin-alone group.

Nonfatal major bleeding was significantly more common with warfarin alone (0.68%/year) and with combined therapy (0.57%/year) than with aspirin alone (0.17%/year). Patients in the warfarin groups also were more likely to withdraw from the study for any reason and specifically because of bleeding.

Comment: This study could make practitioners a bit less certain about the best antithrombotic approach to secondary prevention after MI: The findings turn the tide of research unexpectedly in favor of moderate-intensity warfarin plus aspirin, despite higher withdrawal rates for warfarin users. An editorialist stops short of endorsing combination therapy for all patients but says it should be considered in patients at risk for thromboembolic events and in other appropriate subgroups (e.g., patients with the antiphospholipid syndrome).

— Harlan M. Krumholz, MD, SM

Published in Journal Watch Cardiology November 8, 2002

Citation(s):

Hurlen M et al. Warfarin, aspirin, or both after myocardial infarction. N Engl J Med 2002 Sep 26; 347:969-74.

• Original article (Subscription may be required)
• Medline abstract (Free)

Becker RC. Antithrombotic therapy after myocardial infarction. N Engl J Med 2002 Sep 26; 347:1019-22.

• Original article (Subscription may be required)
• Medline abstract (Free)