1.6 Deriving Baseline Risk of Nonfatal Major Extracranial Bleeding To develop our recommendations, we also required estimates of the baseline risk of nonfatal major extracranial bleeding in patients with AF. We obtained this estimate from observational studies of VKA therapy in cohorts that included exclusively or predominantly patients with AF (median rate of 1.3% per year across these studies).44,53,54 To estimate the baseline risk of non- fatal major extracranial bleeding off VKA therapy, we used this median rate of bleeding on VKA therapy from the observa- tional studies (1.3% per year) and divided by the pooled relative risk (2.58) of nonfatal major extracranial bleeding associated with VKA therapy, as obtained from RCTs of VKA therapy vs no therapy. Therefore, our estimate of the baseline risk of nonfatal major extracranial bleeding off therapy was 0.5% per year. 2.0 Antithrombotic Therapy for Patients With AF in General Over the past 2 decades, numerous RCTs have investigated antithrombotic therapies to reduce the risk of thromboembolism, principally ischemic stroke, in patients with AF. In this section, we summarize the evidence and give treatment recommendations for VKA therapy, antiplatelet monotherapy (eg, aspirin), dual antiplatelet therapy with aspirin and clopid- ogrel, and new oral anticoagulants (eg, dabigatran) in patients with AF. 