Alternate-day dosing of aspirin in atrial fibrillation: A critical evaluation.

Atrial fibrillation is well recognized as an important risk factor for cerebrovascular and systemic embolism. Several randomized trials have demonstrated a benefit of warfarin therapy in reducing the risk of stroke compared with placebo, and there is evidence that warfarin offers better protection than aspirin, except perhaps in patients at low risk for stroke. One proposed mechanism for the benefit of warfarin is the belief that it prevents the development of left atrial appendage thrombus. Atrial fibrillation predisposes the appendage to a relatively stagnant blood pool and creates the substrate for thrombus development. A second proposed mechanism for benefit from antithrombotic strategies is less direct. Common conditions associated with a risk for atrial fibrillation are also risk factors for atherosclerotic vascular disease. Patients with these conditions are at risk of in situ thrombosis. Aspirin has proven benefit in primary and secondary prevention of vascular events in cerebral, peripheral, and coronary circulations and may have use in the setting of atrial fibrillation by potentially preventing or limiting this process. The article by Posada and Barriales1 in this edition of the Journal examines the role of low-dose aspirin therapy in the setting of atrial fibrillation. Both treatment arms, 125 mg every day (A1) and 125 mg every other day (A2) showed a non–statistically significant trend toward decreased cardiovascular events compared with the placebo group. The apparent benefit was seen predominantly in preventing cardiovascular death, the principal cause of death in this study. The study did not demonstrate any significant reduction in disabling or fatal stroke between the treatment arms and the placebo arm (2.6% vs 3.3%, P = .7). The study has major limitations. The sample size was relatively small; the authors acknowledge that the steering committee terminated enrollment after the results of SPAF I and SPAF II (Stroke Prevention in Atrial Fibrillation) were available because of ethical issues of having a placebo group. The lower than expected rate of stroke also contributed to the β error; the authors expected a 12% incidence of stroke over a 2-year period but found a 3.3% incidence in the control group after 12 months. The study population was therefore intermediate in risk for stroke. Based on current teaching these patients could expect a substantial benefit from warfarin. Intermittent dosing of aspirin did show a reduction in stroke compared with placebo (1.1% vs 3.3%, P = .05), whereas daily dosing of aspirin did not demonstrate this benefit (3.8% vs 3.3%, P = not significant). Similarly, intermittent dosing of aspirin suggested a benefit in reducing major vascular events compared with placebo (2.2% vs 11%, P = .001). However, the study was unable to demonstrate a significant difference between the more relevant comparison of intermittent and daily dosing of aspirin for either stroke (P = .4) or survival (P = .8). In our view the authors overstate the conclusion that “aspirin given on alternate days prevents cardiovascular events.” Compelling data to support the use of alternate-day aspirin in atrial fibrillation are not provided by this paper.