Bleeding during warfarin and aspirin therapy in patients with atrial fibrillation - The AFASAK 2 Study

Background: Treatment with warfarin sodium is effective for stroke preventi on in atrial fibrillation but many physicians hesitate to prescribe it to e lderly patients presumably because of the associated risk for bleeding and the inconvenience of frequent blood tests for the patients. Methods:. In the Second Copenhagen Atrial Fibrillation, Aspirin, and Antico agulation (AFASAK 2) Study, we studied the rate of bleeding events associat ed with the incidence of thromboembolic events in patients receiving warfar in sodium, 1.25 mg/d; warfarin sodium; 1.25 mg/d, plus aspirin, 300 mg/d; a spirin, 300 mg/d; or adjusted-dose warfarin therapy aiming at an internatio nal normalized ratio of the prothrombin time ratio (INR) of 2.0 to 3.0. The study was scheduled for 6 years from May 1, 1993, but owing to evidence of inefficiency of low-intensity;therapy plus aspirin from another study it w as prematurely terminated on October 2, 1996. Minor and major bleeding even ts were recorded prospectively. The rate of bleeding was calculated using t he Kaplan-Meier method and risk factors were identified by the Cox proporti onal hazards model. Results: Of 677 included patients, 130 (median age, 77 years; range, 67-89 years) experienced bleeding. One woman and 12 men experienced major bleedin g. Four had intracranial bleeding: 2 cases were fatal and 2 were nonfatal. During treatment with mini-dose warfarin, warfarin plus aspirin, aspirin, a nd adjusted-dose warfarin, the annual rate of major bleeding was 0.8%, 0.3% , 1.4%, and 1.1%, respectively (P =.20). After 3 years of treatment the cum ulative rate of any bleeding was 24.7%, 24.4%, 30.0%, and 41.1% (P =.003), respectively. Increasing INR value (P<.001) and prior myocardial infarction (P =.001) were independent risk factors for bleeding, whereas increasing a ge was not. Conclusions: Fixed mini-dose warfarin and aspirin alone or in combination w ere associated with both minor and major bleeding. The small number of majo r bleeding events in patients receiving adjusted-dose warfarin therapy as c ompared with those receiving less intensive antithrombotic treatments and t he finding of no significant influence of age on the risk for bleeding indi cate that even elderly patients with atrial fibrillation tolerate adjusted dose warfarin therapy (INR, 2.0;3.0).