Direct oral anticoagulants vs. vitamin K antagonists for left ventricular thrombus: a paradigm shift in antithrombotic strategy?

Abstract Background Left ventricular thrombus (LVT) is a critical complication in patients with left ventricular dysfunction, particularly post-myocardial infarction, with high embolic risk necessitating anticoagulation. Despite emerging evidence on direct oral anticoagulants (DOACs), vitamin K antagonists (VKAs) remain the guideline-recommended standard, despite limitations such as a narrow therapeutic window, drug interactions, and frequent monitoring. There is an urgent need to reassess DOACs for LVT management. Objective To compare DOACs vs. VKAs in LVT treatment, focusing on thrombus resolution, embolic risk reduction, and safety outcomes. A secondary aim was evaluating the impact of imaging modalities (contrast echocardiography vs. cardiac magnetic resonance) on thrombus resolution rates. Methods A systematic review and meta-analysis were conducted per PRISMA guidelines, including randomized controlled trials (RCTs) and observational studies comparing DOACs and VKAs for LVT. Primary outcomes: Thrombus resolution at follow-up imaging Systemic embolization (stroke, limb ischemia, mesenteric infarction) Major bleeding (ISTH criteria) All-cause mortality A random-effects model calculated pooled odds ratios (ORs) with 95% confidence intervals (CIs). Bayesian hierarchical modeling estimated posterior probabilities of DOAC superiority. Results 18 studies (n=3,239 patients; DOACs=1,021, VKAs=2,218) met inclusion criteria. Key findings: Higher thrombus resolution with DOACs (OR: 1.21, 95% CI: 1.02–1.46, p=0.03, I²=44%) Lower stroke risk (OR: 0.59, 95% CI: 0.39–0.91, p=0.01, I²=36%) Comparable systemic embolization rates (OR: 0.83, 95% CI: 0.57–1.18, p=0.28, I²=39%) Lower major bleeding risk (OR: 0.72, 95% CI: 0.51–1.03, p=0.07, I²=46%) No difference in all-cause mortality (OR: 0.92, 95% CI: 0.71–1.22, p=0.61, I²=41%) Bayesian analysis showed a 79% probability that DOACs are superior in stroke prevention and a 91% probability that they have a safer bleeding profile. Subgroup Insights Cardiac MRI detected thrombus resolution at a higher rate than echocardiography (p=0.02), supporting standardized imaging follow-up. DOAC efficacy was most pronounced in anterior MI, a group at high embolic risk. Conclusions This meta-analysis suggests DOACs as a viable alternative to VKAs for LVT, offering comparable thrombus resolution and superior stroke prevention with a favorable bleeding profile. These findings support an urgent reassessment of ESC guidelines and call for RCTs to establish DOACs as the preferred anticoagulation strategy.Forest Plot summarizing the key meta-ana