Reversal strategies for non-vitamin K antagonist oral anticoagulants: a critical appraisal of available evidence and recommendations for clinical management - a joint position paper of the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy and European Society of Cardiology Working Group on Thrombosis

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 2.0–3.0.1,2 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, Table S1 and their main effects are summarized in Supplementary material online, Table S2 . The risk of bleeding in patients managed with NOACs was properly assessed in the four landmark Phase III trials in patients with atrial fibrillation (AF; Table 1 ). Major bleeding was the principal safety outcome in RE-LY,3,4 ARISTOTLE,5 and ENGAGE AF.6 In ROCKET-AF, the primary safety endpoint was the composite of major and non-major clinically relevant bleeding.7 The risk of major bleeding was significantly reduced with dabigatran 110 mg b.i.d., apixaban and both doses of edoxaban3–6 while the bleeding rates for dabigatran 150 mg b.i.d. and rivaroxaban were similar to those with warfarin ( Table 1 ). View this table: Table 1 Risk of bleeding with non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation (rates per 100 patients-years) Gastrointestinal (GI) bleeding accounts for ∼90% of major extracranial haemorrhages in patients with AF receiving VKAs.8 With the NOACs, dabigatran 150 mg b.i.d., rivaroxaban, and edoxaban 60 mg o.d. significantly increased rates of GI bleeding (∼1.5-fold) compared with warfarin.3,6,7 While rivaroxaban increases upper and lower GI bleeding …