Authors
Hurlen M, Abdelnoor M, Smith P, et al.
Title
Warfarin, Aspirin, or both after myocardial infarction
References
NEJM 2002;347:969-974.
Background
Aspirin is commonly used for secondary prevention after myocardial infarction. Warfarin is also effective for secondary prevention, however its use is less than aspirin, due to inconvenience. Theoretically, the combination of warfarin and aspirin may provide better clinical effect for secondary prevention due to different mechanisms of action, however results from previous trials testing this hypothesis have been inconsistent.
Purpose
To compare the safety and efficacy of long-term treatment with warfarin alone, aspirin alone, or the combination of aspirin and warfarin for secondary prevention after acute myocardial infarction (MI).
Design
  • Multicenter, randomized, open-label trial
  • 3,630 patients ≤75 years of age hospitalized with acute MI
Exclusion Criteria
None.
Follow-Up
4 years (mean)
Treatment Regimen
  • Warfarin (target INR 2.8-4.2) or
  • Aspirin 160 mg daily or
  • Aspirin 75 mg daily plus warfarin (target INR 2.0-2.5)
Results
Primary endpoint: Composite of death, nonfatal reinfarction, or thromboembolic stroke.

There was a significant reduction in the risk of the primary endpoint with the combination of aspirin and warfarin compared to aspirin alone (risk reduction 29%; p=0.001) and when comparing warfarin to aspirin (risk reduction 19%; p=0.03). There was no mortality difference amongst all treatment groups. The difference between both groups who received warfarin was not significantly different.

Episodes of major, nonfatal bleeding occurred in 0.17% per year of patients receiving aspirin and 0.62% per year in both groups receiving warfarin (p<0.001). Incidence of minor bleeding was also increased in the groups of patients receiving warfarin compared to aspirin alone.
Summary
Warfarin, either alone or in combination with aspirin further reduces the risk of the composite endpoint of death/MI/stroke post-MI, but with a higher risk of bleeding.
Implications
None.
Related Figures
[18]