Risk of thromboembolic events and bleeding in patients with nonvalvular atrial fibrillation after switching from warfarin to direct oral anticoagulant

Abstract: Non-valvular atrial fibrillation (NVAF) increases the risk of thromboembolic events like stroke. Warfarin has been the standard anticoagulant, but direct oral anticoagulants (DOACs) offer alternatives with fewer monitoring needs. NVAF accounts for a significant portion of ischemic strokes, with estimates suggesting that up to 20-30% of all ischemic strokes are attributable to AF, highlighting the critical need for effective anticoagulation strategies. Warfarin, while effective, is associated with challenges such as narrow therapeutic index, drug interactions, and variability in response due to genetic factors like VKORC1 and CYP2C9 polymorphisms. This systematic review and meta-analysis aims to evaluate the risks of thromboembolic events and bleeding in NVAF patients switching from warfarin to DOACs, synthesizing evidence to guide clinical decisions. The review also explores subgroup variations, long-term implications, and real-world applicability to provide a comprehensive framework for clinicians managing anticoagulation therapy transitions. Following PRISMA guidelines, we searched PubMed, Embase, Scopus, and Cochrane Library up to 2025. Included studies compared outcomes in switching patients. Data were pooled using random-effects models in Review Manager 5.4. We conducted sensitivity analyses to assess the robustness of findings and meta-regression to explore sources of heterogeneity, such as study design and patient demographics. Fifteen studies ( n =120,000) showed slightly reduced thromboembolic risk (RR=0.92, 95% CI: 0.82-1.03, P =0.15, I ²=40%) but reduced major bleeding (RR=0.85, 95% CI: 0.75-0.96, P =0.005, I ²=50%) with DOACs. Subgroup analyses favored apixaban for bleeding reduction ( P -interaction=0.02). Mixed results were noted in frail patients, with some studies showing increased bleeding risk upon switching. Additional analyses revealed that the benefits were more pronounced in patients with CHA 2 DS 2 -VASc (C-Congestive heart failure (1 point)/ H-Hypertension (1 point)/ A2-Age ≥ 75 years (2 points)/ D-Diabetes mellitus (1 point)/ S2-Stroke, TIA, or thromboembolism (2 points)/ V-Vascular disease (prior MI, peripheral artery disease, or aortic plaque) (1 point)/ A-Age 65–74 years (1 point)/ Sc-Sex category (female) (1 point)) scores ≥4, and forest plots demonstrated consistent trends across different DOAC agents. Switching to DOACs generally maintains thromboembolic protection while lowering bleeding risk, supporting their use in select high-risk patients. However, caution is advised in frail or elderly populations where bleeding risks may increase. Future guidelines should incorporate these findings to optimize patient selection and monitoring protocols, potentially integrating pharmacogenomic testing for personalized anticoagulation management.