Background: Anticoagulation therapy remains largely underused in older people with atrial fibrillation (AF). The aim of this pilot trial was to investigate the effects of low-intensity adjusted-dose and fixed-dose coumadin on the incidence of arterial thromboembolism and bleeding, as well as the efficacy of anticoagulation monitoring in elderly AF patients.
Methods: In this open-label, randomized trial we recruited patients over 75 years of age without previous stroke or systemic embolism. Patients were randomized into three groups, with group A receiving aspirin 100 mg/day, group B fixed-dose coumadin 1 mg/day; and group C adjusted-dose coumadin with a target range of international normalized ratios (INR) between 1.6 and 2.5. Primary endpoints (ischemic strokes and systemic embolisms) and secondary endpoints (deaths, myocardial infarctions, and major bleeding events) were prospectively documented.
Results: The study was discontinued 6 months after the enrollment of the first patient for safety reasons. During this period, 45 patients were recruited (15 patients in group A, 14 in group B, and 16 in group C). Over a mean follow-up period of 3.7 months (range: 1-6 months), two patients from group B developed a dangerous prolongation of the INR (7.0 and 4.2), which led to the discontinuation of fixed-dose coumadin. Another patient from the same group experienced a major bleeding event 1 month after enrollment in the study (INR: 5.5). The percentage of INR measurements within the target range was significantly (p<0.001) lower in group B (48.7%) than in group C (83.7%).
Conclusions: Older people receiving fixed-dose oral anticoagulants may be at risk of developing a dangerous prolongation of their INR.