In patients with AF, adjusted-dose warfarin and antiplatelet agents reduce the risk for stroke by≈ 65% and by≈ 20%, respectively. 17 However, oral antiplatelet agents do not perform as well as OAC with warfarin in this context. The Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE-W) trial performed in patients with AF plus≥ 1 risk factor for stroke was stopped prematurely because of a clear evidence of superiority of OAC compared with DAPT with aspirin and clopidogrel, particularly in those already receiving OAC at study entry, with no increase in bleeding complications. 18 In a meta-analysis of 6 contemporary randomized clinical trials published between 2002 and 2012, focusing on patients with AF on warfarin therapy, the stroke rates were found to be higher in elderly, female, subjects who were VKAs naïve or those with previous stroke or transient ischemic attack, renal impairment, previous aspirin use, or high CHADS2 (cardiac failure, hypertension, age, diabetes mellitus, stroke [doubled]) score. 19 However, even in the highest risk subgroup (previous stroke), the annualized risk of stroke with warfarin therapy was relatively low (≈ 2.5% per year). These results have corroborated the role of OAC with warfarin as the mainstay of cardioembolic prevention in patients with AF. In contrast, despite its undeniable benefits, warfarin is affected by a number of known limitations, including bleeding complications, dietary or drug interactions, and need for international normalized ratio (INR) monitoring and dose adjustment. These limitations may contribute to explain why only approximately half of patients who would benefit from OAC actually receive warfarin. 20 Patients deemed unsuitable for warfarin therapy may benefit from DAPT with aspirin and clopidogrel, which in the ACTIVE-A trial was shown to reduce the risk of major vascular events and stroke, compared with aspirin alone, at the price of an increased risk of major bleeding. 21 NOACs, which act by directly and selectively inhibiting key coagulation factors such as thrombin (ie, dabigatran) or factor Xa (ie, rivaroxaban and apixaban), have recently entered the market and clinical practice guidelines for the management of patients with nonvalvular AF. 22 NOACs hold several favorable characteristics, including good availability, rapid onset of action, minimal drug/food interaction, no need for coagulation monitoring or dose adjustment, established efficacy and low risk of bleeding. 23 In meta-analyses of warfarin-controlled trials, NOACs have been shown to reduce mortality significantly by 11% to 12%, the combination of stroke and systemic embolism by 18% to 23%, and intracranial hemorrhage by 21% to 54%. 21–54 The annualized absolute risks of stroke or systemic embolism in these pooled analyses have been estimated at 2.4% to 2.8% with NOACs and 3.1% to 3.5% with warfarin. 24, 25