Left atrial appendage occlusion versus NOACs in patients with atrial fibrillation: Rationale and design of the CATALYST Trial.

Background Both percutaneous left atrial appendage occlusion (LAAO) and non-vitamin K antagonist oral anticoagulants (NOACs) are noninferior to warfarin for stroke prevention in high-risk patients with atrial fibrillation (AF). However, there is limited data comparing LAAO with NOACs. The CATALYST trial compares a dual-seal LAAO device (Amplatzer™ Amulet™) to NOACs in AF patients indicated for thromboprophylaxis.Study Design CATALYST is a prospective, multicenter, randomized controlled, open-label trial with an adaptive statistical design. Up to 2,650 AF patients with CHA2DS2-VASc score ≥2 (men) or ≥3 (women) will be randomly assigned to LAAO or NOAC at 123 global sites. Patients randomized to NOACs take the appropriate labeled dose with compliance monitored at each visit, while LAAO patients receive dual antiplatelet therapy followed by aspirin monotherapy for ≥12 months post-implant. Patients are followed through 5 years, with post-implant cardiac imaging at 3- and 12-months. There are three co-primary endpoints: (1) ischemic stroke, systemic embolism, or cardiovascular death through 2 years, tested for noninferiority; (2) major or clinically relevant non-major bleeding through 2 years, tested for superiority; and (3) ischemic stroke or systemic embolism through 3 years, tested for noninferiority. The following secondary endpoints will be tested if the primary endpoints are met: (1) all-bleeding, tested for noninferiority; (2) followed by testing for superiority; (3) disabling or fatal strokes, tested for superiority; all through 2 years.Conclusions CATALYST is evaluating the safety and effectiveness of a dual seal LAAO device compared to NOACs in patients with AF at increased risk of stroke.Clinical Trial Registration URL https://clinicaltrials.gov; Unique Identifier NCT04226547.