Pharmacist University of British Columbia UBC Vancouver, British Columbia, Canada
Background: Direct oral anticoagulants (DOACs) have superseded warfarin in the prevention of thromboembolic complications for most conditions, but their use early after cardiac surgery is limited due to a lack of randomized controlled trials (RCTs) and concerns about bleeding risk. We aimed to conduct a pilot RCT to determine the feasibility of conducting a larger RCT of DOACs after cardiac surgery.
METHODS AND RESULTS: We conducted an open-label, 2-site, pilot RCT of adults undergoing cardiac surgery with an indication for anticoagulation (pre-existing or post-operative atrial fibrillation [AF], venous or arterial thromboembolism, stroke, or mitral valve repair), excluding patients with mechanical valves, bioprosthetic mitral valve replacement, and those at high bleeding risk. We randomized patients 1:1 to DOAC (apixaban, dabigatran, edoxaban, rivaroxaban) or warfarin started during the index hospitalization with a standardized time of post-operative anticoagulation initiation (starting DOAC earliest on postoperative day 5 or day of discharge and starting warfarin 1 day after confirming indication for anticoagulation) and parenteral bridging for those at moderate to high thrombosis risk. The coprimary feasibility outcome goals were recruitment of eligible patients and adherence to the anticoagulation protocol (i.e., appropriate study drug timing of initiation and bridging criteria adherence). The primary scientific outcome was a composite of death, major bleeding, stroke, systemic embolism, or pericardial effusion requiring drainage at 1 and 3 months.
Between October 2022 and February 2024, 547 patients were screened, 163 met inclusion criteria, 104 were randomized, and 100 were analyzed (4 withdrew consent post-randomization - 3 in warfarin and 1 in DOAC group). We recruited 64% of eligible patients (target: ≥70%), with a median monthly recruitment of 5 (range 0-12). Mean age of participants was 69.5 years, 22% were female, mean CHA2DS2-VASc was 2.7, and mean HAS-BLED was 1.6. The most common indications for anticoagulation were pre-existing AF (54%) and post-operative AF (37%). Adherence to the anticoagulation protocol was 91% (target: ≥80%), with the study drug initiated on the appropriate post-operative day in all, and 91% achieved bridging protocol adherence. The primary scientific outcome occurred in four patients receiving DOAC (8%; 3 major bleeding,1 death) and two patients receiving warfarin (4%; 2 strokes).
Conclusion: This pragmatic, pilot RCT demonstrated feasibility with adequate recruitment, high retention and protocol adherence, and low incidence of thromboembolic and bleeding complications. This trial supports the need for and can guide the design of a large, definitive multicenter RCT comparing DOAC versus warfarin in patients undergoing cardiac surgery.
