However, the risk of majorbleeding and ICH is substantially increased with the addition of APT to OAC. The largest cohort was reported by Lamberts et al293 where 8,700 AF patients (mean age, 74.2 years; 38% women) with stable coronary artery disease (de ned as 12 months from an acute coronary event) followed up for a mean 3.3 years, found the risk of MI/coronary death was similar for VKA plus aspirin (HR, 1.12; 95% CI, 0.94-1.34) and VKA plus clopidogrel (HR, 1.53; 95% CI, 0.93-2.52), relative to VKA monotherapy. However, the risk of bleeding increased > 50% when aspirin (HR, 1.50; 95% CI, 1.23-1.82) or clopidogrel (HR, 1.84; 95% CI, 1.11-3.06) was added to VKA. In the RCTs of NOACs compared with warfarin, aspirin at < 100 mg daily was allowed. Ancillary analyses show no added bene t of adding aspirin on stroke or mortality rates; however, absolute bleeding rates were higher with combination therapy, but the relative ef cacy and safety with NOAC vs warfarin use were maintained irrespective of aspirin use.294 Only the RE-LY trial showed data for combination of dabigatran with aspirin and/or clopidogrel, and as expected, major bleeding risks were increased with a single APT and further increased where 2 APTs were used.295 Less data are evident for OAC use in AF patients with stable isolated PAD or carotid disease, in relation to OAC use. However, it is reasonable to assume that data for coronary artery disease would be generally applicable to PAD or carotid disease. 