Direct Oral Anticoagulants Compared to Warfarin Early After Cardiac Surgery: A Pilot Randomized Controlled Trial.

BACKGROUND: The goal was 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, 2-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 receive a DOAC or warfarin started during the index hospitalization with a standardized time of postoperative 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, a total of 547 patients were screened, 163 met inclusion criteria, 104 were randomized, and 100 were analyzed (50 in each group). The median age was 72 years; 22% were female; 54% had preexisting atrial fibrillation; 37% had postoperative atrial fibrillation, with a median Congestive Heart Failure, Hypertension, Age ≥ 75 Years, Diabetes Mellitus, Stroke, Vascular Disease, Age 65 to 74 Years, Sex Category (CHA2DS2-VASc) score of 3 and a Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly (> 65 Years), Drugs/Alcohol Concomitantly (HAS-BLED) score of 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 provides valuable insights into key challenges to mitigate, thereby guiding the design of a large, definitive multicentre RCT comparing DOACs vs warfarin in cardiac surgery patients. CLINICAL TRIAL REGISTRATION: NCT05006287.