www.chestpubs.org CHEST / 141 / 2 / FEBRUARY, 2012 SUPPLEMENT e541S 2.1.2 implies that adjusted-dose warfarin is far supe- rior to aspirin for the prevention of stroke in patients with AF but is likely to be associated with a greater risk of bleeding complications. Direct evidence regarding this clinical question comes from 11 RCTs (total of 6,526 patients) comparing adjusted-dose VKA therapy to antiplatelet monotherapy (AFASAK 1, AFASAK 2, Birmingham Atrial Fibrillation Treat- ment of the Aged [BAFTA], EAFT, National Study for Prevention of Embolism in Atrial Fibrillation [NASPEAF], Primary Prevention of Arterial Throm- boembolism in Nonrheumatic AF in Primary Care Trial [PATAF], Studio Italiano Fibrillazione Atriale [SIFA], SPAF II, SPAF III, Vemmos et al,69 and War- farin vs Aspirin for Stroke Prevention in Octogenar- ians With AF [WASPO]) (Table 5).55,60,70-77 Antiplatelet therapy was typically with aspirin 75 to 325 mg/d, but in the SIFA and NASPEAF studies, it was with indobufen and tri usal, respectively.72,74 In SPAF III and one of the two antiplatelet arms of AFASAK II, aspirin was given in combination with xed mini- dose (ineffective) warfarin.70,76 These trials provide high-quality evidence that adjusted-dose VKA therapy reduces by one-half the risk of nonfatal stroke compared with antiplatelet monotherapy. These trials suggest that VKA therapy increases the risk of nonfatal major extracranial bleeding by about 50% compared with aspirin (pooled risk ratio, 1.42; 95% CI, 0.89-2.29), but the quality of evidence was rated down to moderate because of imprecision. 