Direct oral anticoagulants versus warfarin for left ventricular thrombus: an updated systematic review and meta-analysis of randomized and observational studies.

Background: Left ventricular thrombus (LVT) is associated with substantial risk of embolism and mortality. Given the growing use of direct oral anticoagulants for LVT and evolving evidence, we conducted an updated, comprehensive systematic review and meta-analysis comparing their effectiveness and safety with vitamin K antagonists. Methods: We systematically searched PubMed/MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception through the most recent search date for randomized controlled trials and observational studies comparing DOACs with VKAs in adults with imaging-confirmed LVT. Outcomes of interest included LVT resolution, systemic embolic events, all-cause mortality, bleeding events, and composite clinical outcomes. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using random-effects models. Statistical heterogeneity was assessed using the I² statistic. Results: A total of 29 studies, comprising randomized controlled trials and observational cohorts, were included. Compared with VKAs, DOAC therapy was associated with a numerically higher likelihood of LVT resolution, although this did not reach statistical significance (RR 1.06, 95% CI 0.98-1.14; I² = 48.2%). There was no significant difference in the risk of systemic embolic events between DOACs and VKAs (RR 0.89, 95% CI 0.78-1.03; I² = 5.5%). DOAC use was associated with a lower risk of all-cause mortality (RR 0.84, 95% CI 0.64-1.09; I² = 5.5%); however, this finding was primarily driven by observational data. DOACs were also associated with a lower risk of bleeding events (RR 0.86, 95% CI 0.72-1.03; I² = 16.4%), although this did not reach statistical significance. Conclusions: In this updated meta-analysis, DOACs were associated with a numerically higher rate of LVT resolution, although this did not reach statistical significance, and with lower rates of bleeding compared with VKAs, without an increased risk of systemic embolic events. Although a lower risk of all-cause mortality was observed, this finding was primarily driven by observational studies and should be interpreted with caution. These findings support DOACs as a reasonable and potentially safer alternative to VKAs for the management of LVT, while emphasizing the need for adequately powered randomized trials to confirm optimal anticoagulation strategies in this population. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251181379, PROSPERO CRD420251181379.