Warfarin plus aspirin more effective than aspirin alone for secondary prevention of MI

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Q&A

Warfarin plus aspirin more effective than aspirin alone for secondary prevention of MI

J Fam Pract. 2003 January;52(1):12-31

By

Lee I. Blecher, MD

Alex Krist, MD

BACKGROUND: Is warfarin plus aspirin or high-dose warfarin more effective than aspirin alone to prevent a second heart attack? Researchers have found conflicting results as to whether warfarin is better than aspirin in preventing a second myocardial infarction in patients with established coronary artery disease. A meta-analysis suggested that high-intensity warfarin or moderate-intensity warfarin plus aspirin is more effective than aspirin alone.¹ This study is the latest and largest one to address this question.
POPULATION STUDIED: The investigators studied 3630 men and women younger than 75 years admitted for acute myocardial infarction. Acute myocardial infarction was defined as typical chest pain, appropriate electrocardiogram changes, and a creatinine kinase level higher than 250 U/L or an aspartate aminotransferase level higher than 50 U/L. The investigators excluded patients with contraindications to study drugs, malignant disease, or anticipated poor compliance. Control and intervention groups were similar with respect to comorbid diseases, medication usage, and demographics.
STUDY DESIGN AND VALIDITY: This study was a randomized, open label, multicenter investigation based in Norway. The intervention groups were a warfarin group (goal: international normalized ratio [INR], 2.8–4.3) and a warfarin plus aspirin group (goal: INR, 2–2.5, plus 75 mg of aspirin daily). The control group received 160 mg of aspirin daily. Patients were followed for a mean of 4 years with clinical examinations conducted in the general practice setting. Every 6 months subjects received questionnaires assessing compliance, adverse events, and new thromboembolic events.
OUTCOMES MEASURED: The primary outcome was a combined outcome of death, re-infarction, or thromboembolic stroke. The researchers also measured major and minor bleeding events. Major bleeding was defined as a cerebral hemorrhage or any blood loss requiring surgery or transfusion.
RESULTS: The risk of death, reinfarction, or thromboembolic stroke was significantly decreased when warfarin was used: 15% for the warfarin plus aspirin group and 16.7% for the warfarin group vs 20% for the aspirin group. This correlated with a relative risk of 0.71 for the warfarin-plus-aspirin group (95% confidence interval [CI], 0.60–0.83; number needed to treat [NNT=67 per year) and 0.81 for the warfarin group (95% CI, 0.69–0.95; NNT=100 per year) compared with aspirin alone. Relative risk reduction in the composite outcome was due primarily to a decrease in re-infarction (relative risks of 0.56 and 0.74 for the warfarin and warfarin plus aspirin groups, respectively) and thromboembolic stroke (relative risks of 0.52 and 0.52 for the warfarin and warfarin plus aspirin groups, respectively). There was no difference in mortality among groups. Major bleeding episodes were more common in the warfarin-plus-aspirin group (0.57% per year; number needed to harm [NNH] = 250 per year) and the warfarin group (0.68% per year; NNH=200 per year) than in the aspirin group (0.17% per year). There were no statistical differences in benefit or harm between the intervention groups. Nearly 33% of patients in the intervention groups needed to discontinue warfarin at some point.

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Warfarin plus aspirin more effective than aspirin alone for secondary prevention of MI

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