Direct Oral Anticoagulants vs Vitamin K Antagonists for Left Ventricular Thrombus: A Time-Dependent Meta-Analysis with Trial Sequential and Influence Analyses

Background Left ventricular thrombus (LVT) is a serious thromboembolic complication of cardiac dysfunction. Vitamin K antagonists (VKAs) are the historical standard therapy, but have limitations. While direct oral anticoagulants (DOACs) offer practical advantages, their efficacy and safety in LVT remain uncertain. This meta-analysis aimed to compare the efficacy and safety of DOACs versus VKAs for the treatment of LVT. Methods We conducted a meta-analysis by systematically searching electronic databases from inception to December 2025. A random-effects model was used for all analyses. The primary outcome was LVT resolution. Secondary outcomes included ischemic stroke, non-cerebral systemic embolism (SE), the composite of stroke and SE, any bleeding, major bleeding, and mortality. Results A total of 35 studies (7 RCTs and 28 retrospective cohort studies), with 6,437 patients (DOACs n = 2,421, VKAs n = 4,016), were included in the analysis. DOACs showed a non-significant trend toward higher LVT resolution than VKAs (odds ratio [OR] 1.17; 95% confidence interval [CI] 0.99–1.39). DOACs were associated with a lower risk of stroke (OR 0.77, 95% CI 0.65–0.92), while SE rates remained comparable (OR 0.79, 95% CI 0.54–1.15). DOACs were associated with a significantly lower risk of major bleeding compared to VKAs (OR 0.62, 95% CI 0.48–0.79; p < 0.001). When analyses were limited to only randomized trials or post–acute coronary syndrome, efficacy and safety were similar across anticoagulants. Trial sequential analysis indicated indecisive results, highlighting the need for further clinical trials. Conclusions DOACs showed overall efficacy similar to VKAs for the treatment of LVT, with lower rates of major bleeding. Despite the large number of included studies, the current evidence base remains inconclusive due to the predominance of observational studies, underscoring the need for additional large, well-designed clinical trials.