Critique of Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation Trial
Cardiogenic embolism in atrial fibrillation (AF) causes 15% to 20% of all ischemic strokes. For 2 decades, there has been solid evidence that strokes in AF can be prevented much more effectively by oral anticoagulants than by antiplatelets.1 Shockingly, it has remained a daily experience of stroke physicians that stroke in patients with known AF has not been adequately prevented.2 This corresponds to registries consistently reporting that only ≈60% of eligible patients with AF are actually anticoagulated. Vitamin K antagonists (VKAs) are inconvenient because they require coagulation monitoring and frequent dose adjustments. Moreover, patients and physicians are concerned about major bleeding complications particularly in the elderly.
Insufficient acceptance of VKAs has led to the development of direct oral anticoagulants (DOACs). DOACs target a single-activated key coagulation factor and result in largely predictable anticoagulation without the need for coagulation monitoring. Three previous large randomized trials have shown consistently that DOACs are at least as effective as warfarin for prevention of stroke in AF.3–5 Remarkably, the direct thrombin inhibitor dabigatran and the factor Xa inhibitors, rivaroxaban and apixaban, also halved the incidence of intracerebral hemorrhage, the most feared complication of long-term anticoagulation. Weighing safety and efficacy of DOACs versus warfarin, European and American guidelines are in favor of starting patients with first diagnosed AF on DOACs, but there is a debate whether stable stroke-free patients on VKA should be switched to DOACs.
The Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation (ENGAGE-AF) trial has added valuable information to the matter.6 ENGAGE-AF, the latest and largest trial of a DOAC, was a randomized, double-blind, double-dummy trial comparing 1 of 2 doses of edoxaban to dose-adjusted warfarin (target international normalized ratio, 2–3). The edoxaban doses were 30 and 60 mg once daily. The edoxaban dose was …