EFFECT OF LOW-INTENSITY WARFARIN ANTICOAGULATION ON LEVEL OF ACTIVITYOF THE HEMOSTATIC SYSTEM IN PATIENTS WITH ATRIAL-FIBRILLATION

Background and Purpose: The Boston Area Anticoagulation Trial for Atri al Fibrillation (BAATAF) demonstrated that low-intensity warfarin anti coagulation can, with safety, sharply reduce the rate of stroke in pat ients with nonvalvular atrial fibrillation. The beneficial effect of w arfarin was presumably related to a decrease in clot formation in the cardiac atria and subsequent embolization. Methods: To assess the effe ct of warfarin therapy on in vivo clotting in patients in the BAATAF, we measured the plasma level of prothrombin activation fragment F1+2. One sample was obtained from 125 patients from the BAATAF; 62 were tak ing warfarin and 63 were not taking warfarin (control group). Results: The warfarin group had a 71% lower mean F1+2 level than the control g roup (mean F1+2 of 1.57 nmol/L in the control group compared with a me an of 0.46 nmol/L in the warfarin group; P<.001). F1+2 levels were hig her in older subjects but were consistently lower in the warfarin grou p at all ages. Fifty-two percent of patients in the control group were taking chronic aspirin therapy at the time their F1+2 level was measu red. Control patients taking aspirin had F1+2 levels very similar to c ontrol patients not taking aspirin (mean of 1.52 nmol/L for control pa tients on aspirin compared with 1.64 nmol/L for control patients off a spirin; P>.1). Conclusions: We conclude that prothrombin activation wa s significantly suppressed in vivo by warfarin but not aspirin among p atients in the BAATAF. These findings correlate with the marked reduct ion in ischemic stroke noted among patients in the warfarin treatment group observed in the BAATAF.