SAFETY AND ANTICOAGULATION EFFECT OF A LOW-DOSE COMBINATION OF WARFARIN AND ASPIRIN IN CLINICALLY STABLE CORONARY-ARTERY DISEASE

The hypothesis that the combination of low-dose aspirin and warfarin t herapy is more effective than aspirin alone in secondary prophylaxis a fter myocardial infarction is to be examined in the Coumadin Aspirin R einfarction Study. This pilot study addressed the safety and anticoagu lation effect of a fixed, low-dose combination in 114 patients (aged 6 4 +/- 8 years, 85% men) with stable coronary artery disease receiving 3 mg of warfarin plus 80 mg of aspirin daily for 8 weeks. The internat ional normalized ratio (INR) was measured within 72 hours of Initial t herapy, and weekly. Of the 110 patients with evaluable INRs, 87 patien ts (79%) maintained the 3 + 80 mg combination, 19 (17%) had the dose r educed to 1 mg warfarin + 80 mg aspirin, and 4 (4%) discontinued thera py because of a confirmed INR of greater than or equal to 4.5. At stea dy state, patients had INRs of 1.48 +/- 0.41 (3 + 80 mg group) and 1.2 1 +/- 0.23 (1 + 80 mg group), and inter- and intra-patient variability (estimated by the mean of the between and within-patient SDs at stead y state) was 0.49 +/- 0.08 and 0.13 +/- 0.14, respectively. There was no apparent effect of age on INR distribution. Microscopic hematuria w as the most frequent (20%) adverse clinical event, but was unrelated t o the INR. Three patients required discontinuation of therapy because of bleeding events (persistent hematuria and epistaxis). A fixed low-d ose combination of warfarin and aspirin results in a predictable and s table increase in the INR in a large proportion of patients with coron ary artery disease. Provided that early INR testing is undertaken in o rder to identify patients with significant sensitivity to low-dose war farin and to establish steady-state