For patients who are unsuitable for or choose not to take an oral anticoagulant (for reasons other than concerns about major bleeding), we recommend combi- nation therapy with aspirin and clopidogrel rather than aspirin (75 mg to 325 mg once daily) (Grade 1B). 2.1.11 Recommendation Regarding Dabigatran vs Adjusted-Dose VKA Therapy: The RE-LY trial showed that dabigatran, at the higher dose of 150 mg bid, leads to reductions in nonfatal stroke, probable reductions in all-cause mortality, and no apparent increase in the risk of nonfatal major extracranial bleeding compared with VKA therapy (Table 9), whereas there was no evidence that dabigatran 110 mg bid leads to a signi cant reduction in relevant outcomes compared with VKA therapy (Table 10). In the United States, the Food and Drug Administra- tion approved the use of dabigatran for the preven- tion of thromboembolism in patients with AF at a dose of 150 mg bid but not at a dose of 110 mg bid. However, the Food and Drug Administration did approve, based on pharmacokinetic considerations rather than direct evidence from RCTs in AF popula- tions, a dose of 75 mg bid for patients with severe renal insuf ciency (de ned as a creatinine clearance For the question of whether to use dabigatran vs adjusted-dose VKA therapy, the evidence suggests net clinical bene t at the 150-mg dose. At the time of this writing, however, knowledge regarding the ef cacy and safety of the new oral anticoagulants for patients with AF is still limited to one large ran- domized trial per agent. Uncommon but serious adverse effects may emerge with large-scale use of the drugs. Performance in usual clinical care may deteriorate because of less-restricted patient selec- tion and suboptimal adherence to the unmonitored drug. 