Warfarin plus aspirin after myocardial infarction or the acute coronary syndrome: Meta-analysis with estimates of risk and benefit

Background: After the acute coronary syndrome, adding warfarin to standard aspirin therapy decreases myocardial infarction and stroke but increases major bleeding. Purpose: To quantify the risks and benefits of warfarin therapy after the acute coronary syndrome. Data Sources: MEDLINE from 1990 to October 2004. Additional data were obtained from study authors. Clinical risk factors were used to classify hypothetical patients into cardiovascular and bleeding risk groups on the basis of published data. Study Selection: Randomized trials comparing intensive warfarin therapy (international normalized ratio > 2.0) plus aspirin with aspirin alone after the acute coronary syndrome. Data Extraction: Two reviewers independently selected studies and extracted data on study design; quality; and clinical outcomes, including myocardial infarction, stroke, revascularization, death, and major and minor bleeding. Rate ratios for outcomes were calculated and pooled by using the method of DerSimonian and Laird. Data Synthesis: Ten trials involving a total of 5938 patients (11 334 patient-years) met the study criteria. Compared with aspirin alone, warfarin plus aspirin was associated with a decrease in the annual rate of myocardial infarction (0.022 vs. 0.041; rate ratio, 0.56 [95% CI, 0.46 to 0.69]), ischemic stroke (0.004 vs. 0.008; rate ratio, 0.46 [CI, 0.27 to 0.77]), and revascularization (0.115 vs. 0.135; rate ratio, 0.80 [CI, 0.67 to 0.95]). Warfarin was associated with an increase in major bleeding (0.015 vs. 0.006; rate ratio, 2.5 [CI, 1.7 to 3.7]). Mortality did not differ. Limitations: Two large studies provided most of the data. Studies did not include coronary stenting, and results should not be applied to patients with stents. Relative risk reductions may not be consistent across risk groups. Conclusions: For patients with the acute coronary syndrome who are at low or intermediate risk for bleeding, the cardiovascular benefits of warfarin outweigh the bleeding risks.