In the Wake of OCEANIC-AF, Is Equipoise Regarding Factor XI Inhibition Still Afloat?

Abstract

Although factor Xa inhibitors reduce intracranial hemorrhage vs vitamin K antagonists in atrial fibrillation (AF),¹ concerns regarding nonintracranial bleeding have led to the development of factor XI/XIa inhibitors, which offer the promise of uncoupling pathologic thrombosis from normal hemostasis. Although phase 2 and 3 studies support the safety of factor XI/XIa inhibition in a variety of settings, the premature termination of OCEANIC-AF (Oral FXI(a) Inhibition Compared to Standard Therapy in Patients With Atrial Fibrillation) because of the inferior efficacy of asundexian compared to apixaban² has raised important questions. Is this a class effect? Is there still equipoise regarding the efficacy of factor XI/XIa inhibitors? To represent a therapeutic advance, the right drug must be administered at the right dose to the right subject. The results of OCEANIC-AF can be evaluated in the context of this drug development paradigm.