Rationale and design of a randomized study comparing the Watchman FLX device to DOACs in patients with atrial fibrillation

Abstract

Percutaneous left atrial appendage (LAA) closure (LAAC) was developed as a non-pharmacological alternative to oral anticoagulants (OACs) in patients with atrial fibrillation (AF) who are at an increased risk for stroke or systemic embolism. The Watchman device permanently seals off the LAA to prevent thrombi from escaping into the circulation. Previous randomized trials have established the safety and efficacy of LAAC compared to warfarin. However, direct OACs (DOACs) have become the preferred pharmacological strategy for stroke prevention in patients with AF, and there is limited data comparing Watchman FLX to DOACs in a broad AF patient population. CHAMPION-AF is designed to prospectively determine whether LAAC with Watchman FLX is a reasonable first-line alternative to DOACs in patients with AF who are indicated for OAC therapy. A total of 3000 patients with a CHA2DS2-VASc score ≥2 (men) or ≥3 (women) were randomized to Watchman FLX or DOAC in a 1:1 allocation at 142 global clinical sites. Patients in the device arm were to be treated with DOAC and aspirin, DOAC alone, or DAPT for at least 3 months post-implant followed by aspirin or P2Y12 inhibitor for 1-year. Control patients were required to take an approved DOAC for the duration of the trial. Clinical follow-up visits are scheduled at 3- and 12-months, and then annually through 5 years; LAA imaging is required at 4 months in the device group. Two primary endpoints will be evaluated at 3 years: (i) composite of stroke (ischemic/hemorrhagic), cardiovascular death, and systemic embolism compared for non-inferiority, and (ii) non-procedural bleeding (International Society on Thrombosis and Haemostasis [ISTH] major and clinically relevant non-major bleeding) tested for superiority in the device arm against DOACs. The third primary non-inferiority endpoint is the composite of ischemic stroke and systemic embolism at 5 years. Secondary endpoints include 3- and 5-year rates of (i) ISTH-defined major bleeding and (ii) the composite of cardiovascular death, all stroke, systemic embolism, and non-procedural ISTH bleeding. This study will prospectively evaluate whether LAAC with the Watchman FLX device is a reasonable alternative to DOACs in patients with AF.