Prevention of thrombus formation after plaque rupture is thought to reduce further cardiovascular events after myocardial infarction. Studies report a 25 percent reduction in vascular events with short-term antiplatelet therapy (including aspirin) and a 35 percent reduction with long-term warfarin therapy. Van Es and colleagues used a Dutch family-practice research network to compare three anticoagulation regimens following acute myocardial infarction.

They studied nearly 1,000 patients admitted to hospitals because of acute myocardial infarction or unstable angina. Patients with conditions that required platelet inhibitors or anticoagulation, such as atrial fibrillation or prosthetic heart valve, and those with serious risk of bleeding or adverse outcome from anticoagulation were excluded from the study. Patients planning a revascularization procedure and those with anemia or a history of stroke also were excluded. Patients were randomly assigned to therapy with low-dosage (80 mg per day) aspirin; warfarin, with a target International Normalized Ratio (INR) of 3.0 to 4.0; or low-dosage aspirin plus anticoagulants, with a target INR of 2.0 to 2.5.

Patient follow-up was performed by family physicians and a regional anticoagulation clinic. Questionnaires and patient records were used to gather data on vascular events and adverse effects of treatment every three months for a maximum of 26 months.

The mean age of the 993 patients for whom data were analyzed was 61 years, and approximately 75 percent of participants were men. Myocardial infarction was diagnosed in more than 85 percent, and 13 percent of patients were diagnosed with unstable angina. The prevalence of risk factors was high. About one half of the patients were smokers, 36 to 40 percent had hypercholesterolemia, 20 to 27 percent had hypertension, and more than 30 percent had a family history of cardiovascular disease.

The three treatment groups were comparable in demographic and significant clinical variables. During the study, 10 percent of the aspirin group, 19 percent of the warfarin group, and 20 percent of the combination-therapy group discontinued treatment. Mean INR levels in the target range were obtained in about one half of patients taking high-intensity warfarin and in about 40 percent of those taking combination therapy. The rates of vascular death, myocardial infarction, or stroke were significantly lower in patients who took warfarin (5 percent) or combination therapy (5 percent) than in patients who took aspirin alone (8 percent).

Patients who took aspirin also showed a nonsignificantly higher rate of unstable angina (7 percent compared with 5 percent) and revascularization procedure (12 percent compared with 10 percent). Rates of major bleeding events were low in all three groups (i.e., 1 percent per patient-year for aspirin and warfarin alone compared with 2 percent per patient-year for combination therapy). Rates of minor bleeding were significantly higher in combination therapy (15 percent) and war-farin treatment (8 percent) compared with aspirin alone (5 percent).

The authors conclude that either high-intensity warfarin therapy or the combination of aspirin plus medium-intensity oral anticoagulants is more effective than aspirin alone in reducing death and serious cardiovascular events following myocardial infarction. The combination therapy was, however, associated with a doubling of rare major bleeding events and a tripling of minor bleeding complications.