Direct oral anticoagulants compared to warfarin early after cardiac surgery: a pilot randomized controlled trial

Background: To conduct a pilot randomized controlled trial (RCT) of direct oral anticoagulants (DOACs) early after cardiac surgery to determine the feasibility of a larger RCT.Methods: We conducted an open-label, two-site, pilot RCT of adults undergoing cardiac surgery with an indication for anticoagulation, excluding mechanical valves and bioprosthetic mitral valve replacements.We randomized patients 1:1 to DOAC or warfarin started during the index hospitalization with a standardized time of post-operative initiation and bridging for high thrombosis risk.The coprimary feasibility outcome goals were recruitment of 70% eligible patients and adherence to the anticoagulation protocol in 80% patients.The primary clinical composite outcome included all-cause mortality, major bleeding, stroke, systemic embolism, or pericardial effusion requiring intervention within 3 months.Results: Between October 2022 and February 2024, 547 patients were screened, 163 met inclusion criteria, 104 were randomized, and 100 were analyzed (50 in each group).Median age was 72 years, 22% were female, 54% had pre-existing atrial fibrillation, 37% had post-operative atrial fibrillation, with median CHA2DS2-VASc 3 and HAS-BLED 2. We recruited 64% of eligible patients and anticoagulation protocol adherence was 91%.The clinical composite outcome occurred in 8% with DOAC (2 major bleeding, 1 pericardial effusion, 1 death) vs 4% with warfarin (2 strokes); log-rank p=0.42. Conclusions:Although the a priori recruitment goal was not met, this trial supports the need for and gains valuable insights into key challenges to mitigate, which guides the design of a large, definitive multicenter RCT comparing DOACs versus warfarin in cardiac surgery patients.Registration of clinical trial: Clinicaltrials.govNCT05006287 (registered 2021-08-16)