Direct oral anticoagulants versus vitamin K antagonists for postoperative atrial fibrillation after cardiac surgery: a systematic review and meta-analysis of randomized controlled trials

Postoperative atrial fibrillation (POAF) is a common complication after cardiac surgery. Although direct oral anticoagulants (DOACs) have revolutionized stroke prevention in non-surgical atrial fibrillation, their role relative to vitamin K antagonists (VKAs) specifically in POAF is unclear. A systematic review and meta-analysis were performed from randomized controlled trials comparing DOACs (apixaban, rivaroxaban, or dabigatran) vs. VKAs in adult patients with POAF following cardiac surgery. The primary outcomes included stroke/systemic embolism as an efficacy endpoint and major bleeding as a safety endpoint. Secondary outcomes comprised any bleeding and cost-effectiveness. We searched the following databases: PubMed, Scopus, Cochrane Central, and Google Scholar from inception through November 2025. The study protocol was registered with PROSPERO (Registration number: CRD420251249764). Four randomized controlled trials (RCTs) were included (n = 202 patients). Stroke/systemic embolism occurred in 1.0% (1/103) of DOAC patients versus 1.0% (1/99) of VKA patients (RR 0.80, 95% CI 0.06–11.5; P = 0.87). Major bleeding occurred in 1.9% (2/103) versus 4.0% (4/99) (RR 0.55, 95% CI 0.11–2.64; P = 0.46). Any bleeding occurred in 10.7% (11/103) versus 11.1% (11/99) (RR 1.01, 95% CI 0.31–3.30; P = 0.99). Two trials reported lower costs with DOACs in their local settings, though these findings are exploratory and not generalizable. Among patients with POAF following cardiac surgery, DOACs appear to have efficacy and safety profiles similar to those of VKAs, with non-significant trends toward lower major bleeding rates. Reported cost advantages are preliminary and context-specific. These findings are based on a small number of trials with limited sample sizes and very low event rates, and do not demonstrate equivalence; they warrant confirmation in larger, adequately powered studies.