In optimizing anticoagulation therapy, it is essential to balance treatment efficacy with the major adverse effect of anticoagulant treatment, bleeding risk. This narrative review examines the efficacy and safety of the non-vitamin K antagonist oral anticoagulants (NOACs) dabigatran, rivaroxaban, apixaban, and edoxaban compared with standard anticoagulation or placebo. NOAC therapies provide equivalent to superior protection versus standard therapy, with similar or superior safety, and potential benefits in convenience. We will review the phase III evidence for each of the available NOACs in different antithrombotic indications, including atrial fibrillation (in the absence of significant mitral stenosis or mechanical heart valves); prophylaxis of venous thromboembolism (VTE) in patients undergoing orthopedic surgery; and acute and long-term treatment of VTE. Further, we will illustrate scenarios in which the evidence is stronger for a particular agent in the context of the overall positive safety and efficacy profile of NOACs in general. Limitations of the factor Xa inhibitors include the lack of a specific antidote in case of a bleeding emergency (an approved agent is available for reversing the effect of the direct thrombin inhibitor). We discuss the options for mitigating bleeding and describe the ongoing developments towards specific reversal agents. In conclusion, the available data for efficacy and safety, together with reliable pharmacokinetics obviating the need for regular monitoring, indicate that NOACs may offer substantial benefits for patients with nonvalvular atrial fibrillation or VTE.
PMID: 30270775 [PubMed - as supplied by publisher]