Efficacy and Safety of Direct-Acting Oral Anticoagulants Versus Warfarin in Patients With Mechanical Valve Replacement

Abstract

This systematic review and meta-analysis aimed to compare the safety and efficacy of direct-acting oral anticoagulants (DOACs) and warfarin in patients with mechanical heart valves, specifically assessing the risks of ischemic stroke, thromboembolism, and major hemorrhage. We included randomized controlled trials (RCTs) that compared DOACs with warfarin, reporting on ischemic stroke, thromboembolism, and major hemorrhage as outcomes. Studies were excluded if they were observational, lacked relevant data, or did not meet the inclusion criteria specified and were extracted from PubMed, Cochrane Central, ClinicalTrials.gov, and Embase with the last search conducted in January 2025. The Cochrane Risk of Bias tool was used to assess the quality of the included studies. A meta-analysis was conducted using the inverse variance method with a fixed-effect model to pool OR with 95% CI for each outcome. Two studies with a total of 1115 participants were included. The DOAC group showed a significantly higher risk of ischemic stroke (OR: 17.42, P=0.005) and thromboembolism (OR: 3.58, P=0.001) compared to warfarin. No significant difference was found in the risk of major hemorrhage (OR: 0.89, P=0.70). The limitations of this review include the small number of included studies and the substantial heterogeneity in the thromboembolism outcomes (Chi²=0.03). There is also a potential for publication bias, as studies with negative or inconclusive results may be underrepresented. Additionally, inconsistencies in how thromboembolism and hemorrhagic events were defined across studies could have affected the outcome assessments. As a result, this meta-analysis implies that clinicians should exercise caution when prescribing DOACs to high-risk populations. Future studies, particularly larger, high-quality RCTs, are needed to further investigate these findings and to explore specific patient subgroups. No financial support was received for this review. This review was registered with PROSPERO (ID CRD42024625615) on December 12, 2024, prior to study search and data extraction.