With regard to primary stroke prevention, convincing evidence favoring the efficacy of anticoagulants in the prevention of embolism in patients with atrial fibrillation came from the Boston Area Anticoagulant Trial for Atrial Fibrillation in 1990. Initially, patients younger than 65 years of age in this and other trials did not clearly benefit from long-term prophylactic anticoagulation unless there were additional cerebrovascular risk factors such as diabetes, hypertension, congestive heart failure, or cardiac valvular disease but newer studies have extended this age range for those with atrial fibrillation. (Those younger than 65 years old and without such additional features [formerly called lone fibrillators], constituting about one-third of adults with atrial fibrillation, have a low risk of stroke). In order to estimate the risk of stroke in atrial fibrillation, including age as a factor so as to address those younger than 65, two variants of what are termed CHADS scores have been developed as summarized in Table 33-3.
Aspirin does not appear to afford the same degree of protective benefit as does anticoagulation for primary risk stroke reduction in atrial fibrillation, and some studies suggest if there are no other risk factors for stroke, there may be slightly better risk reduction for stroke with aspirin than with no treatment. For patients under age 65 and without other risk factors for stroke, reflected usually by a low CHADS score, aspirin may be reasonable preventive measure. The appropriate dose of aspirin has not been established but former trials of very large doses, for example, 1 g/d, conferred risk of bleeding.
A determination of prothrombin and partial thromboplastin activity is needed before therapy is started with warfarin, but if this is not feasible, the initial doses of anticoagulant drugs can usually be given safely if there is no clinical evidence of bleeding anywhere in the body and there has been no recent surgery. Warfarin, beginning with a dose of 5 to 10 mg daily, is relatively safe provided that the international normalized ratio (INR) is brought only to 2 to 3 (formerly measured as a prothrombin time between 16 and 19 s) and the level is determined regularly (an approximate plan is once a day for the first 5 days, then 2 or 3 times a week for 1 to 2 weeks, and finally once every several weeks).
Numerous drugs may alter the anticoagulant effects of the coumarins or add to the risk of bleeding—aspirin, cholestyramine, alcohol, carbamazepine, cephalosporin and quinolone antibiotics, sulfa drugs, and high-dosage penicillin being the most important ones. Hemorrhagic skin necrosis is a rare but dangerous complication. It is the result of a paradoxical microthrombosis of skin vessels and is liable to occur in patients with unsuspected deficiencies of endogenous clotting proteins (S and C). Although the disseminated form of skin necrosis occurs within days of initiating warfarin therapy, we have seen one patient with a form of this lesion following local skin injury after months on treatment.