How safe are non-vitamin K antagonist oral anticoagulants in atrial fibrillation?

Abstract

The development of non-vitamin K antagonist oral anticoagulants (NOACs), also formerly referred to as ‘new’, or ‘novel’, or ‘direct’ oral anticoagulants, in atrial fibrillation (AF) has involved the organization and performance of clinical trials overall accruing experience in over 80,000 patients, approximately 10 times more than patients ever tested with vitamin K antagonists (VKAs) against placebo or aspirin. These drugs were originally developed with the aim of providing practical alternatives to VKAs, not requiring anticoagulation monitoring, and with fixed dosing. They are, however based on this large clinical trial experience now considered to be overall ‘better’ than VKAs, and are therefore currently recommended as the first option of treatment in the vast majority of patients with AF. An important part of their quick acceptance by the international community is their overall better safety compared with VKAs. However the concept of safety is complex and multi-faceted, and can be analyzed in terms of major bleeding, intracranial hemorrhage, mortality, or other criteria. While not all doses of NOACs tested in phase III comparative trials against warfarin have shown less major bleeding or less overall death, all NOACs, at all doses tested, have shown less intracranial hemorrhage. More importantly, all NOAC doses tested appear to show a ‘net clinical benefit’ compared with warfarin. This article expands on the concept of the ‘net clinical benefit’ and on how this may inform clinical decisions, reinforcing the perception of NOACs as better drugs than VKAs in preventing stroke in AF.