Introduction

Atrial fibrillation (AF) has been described as an ‘epidemic’ and affects over 35 million people worldwide (1), whilst incidence and prevalence continue to grow. Cardioembolic stroke is devastating and a major risk for patients with AF. Anticoagulation is a crucial component of AF management in those with risk factors for stroke (2). Direct oral anticoagulants (DOACs) are now used in the majority of patients on oral anticoagulants (OACs) in the UK (3,4), though many still use warfarin.

Despite the favourable safety and efficacy of DOACs, a significant bleeding risk remains (5,6). Major bleeding increases mortality (5) and concerns over bleeding may lead to discontinuation, underuse or inappropriate under-dosing of OACs (7). According to registry data, approximately 40-60% eligible for OACs are not prescribed them (7–9) though there is large variation between institutions and regions (10). Furthermore, amongst those prescribed OACs, approximately one-fifth may be inappropriately under-dosed, a strategy which fails to minimise bleeding risk but may increase mortality (11).

Factor XI (FXI) inhibitors are novel experimental agents that offer the enticing possibility of reducing thromboembolic risk in AF with minimal bleeding risk. This editorial aims to review the rationale for FXI inhibition in AF-related stroke prevention, and the results from the recent PACIFIC-AF study (12).