Bleeding is the main adverse effect when using oral anticoagulants (OACs). The risk of major bleeding with vitamin K antagonists (VKAs) is dependent on the quality of anticoagulation control and estimated to be 1.3/100 patients/year in patients with INR 2.0–3.0. Multiple limitations of VKAs stimulated the development of non-vitamin K antagonist oral anticoagulants (NOACs) acting directly on coagulation factors, including factor FIIa (thrombin) and FXa. Pharmacological properties of the NOACs relevant for bleeding are summarized in the supplement including Supplementary material online and their main effects are summarized in Supplementary material online. The risk of bleeding in patients managed with NOACs was properly assessed in the four landmark Phase III trials in patients with atrial fibrillation. Major bleeding was the principal safety outcome in RE-LY, ARISTOTLE, and ENGAGE AF. In ROCKET-AF, the primary safety endpoint was the composite of major and non-major clinically relevant bleeding. The risk of major bleeding was significantly reduced with dabigatran 110 mg b.i.d., apixaban and both doses of edoxaban while the bleeding rates for dabigatran 150 mg b.i.d. and rivaroxaban were similar to those with warfarin.
Eur Heart J (2017) 38 (22): 1710-1716.