<h3>Introduction</h3> Left ventricular thrombus (LVT) is encountered in patients with poor ventricular function or following acute myocardial infarction (AMI). Furthermore, incorporating oral anticoagulants into dual antiplatelet therapy for AMI adds complexity. While conventional guidance favours vitamin K antagonists (VKAs), emerging evidence suggests favourable outcomes with direct oral anticoagulants (DOACs). <h3>Purpose</h3> To assess the safety and efficacy of DOACs versus VKAs in managing LVT among patients with and without recent acute coronary syndrome (ACS). <h3>Methods</h3> This was a retrospective observational study conducted within TriNetX, a global federated health research network with access to electronic medical records (EMRs) from participating health care organizations including academic medical centres and community hospitals covering approximately 70 million individuals, mainly in the United States. The search was conducted on 26th Februrary 2024 with a study cohort comprising patients with LV thrombus treated with either DOAC or VKA between 1st December 2013 to 1st December 2023. Subgroup analyses were conducted for patients with ACS within one month and those without ACS within a month of treatment. Cohort data were subject to propensity score matching (PSM) for age, gender, ethnicities, medical and drug history. Outcomes of interest was (1) all cause death, (2) stroke, (3) systemic embolism and (4) intracranial or gastrointestinal bleeding. Risk analysis and Kaplan-Meier survival analysis were computed for each subgroup at 90 days since the indexed event. <h3>Results</h3> Following PSM, a total of 39,770 patients were included and 14,302 were in the ACS group with 7151 on DOACs and 7151 on VKAs (mean age 61.6 SD 16.5 vs 61.4 SD 16.1 years, 33.9% vs 34% female) and 24,162 in the non-ACS group with 12081 on DOACs vs 12081 on VKAs (mean age 62.2 SD 14.4 vs 62.4 SD 14.0 years; 29.3% vs 28.9% female). DOAC treatment exhibited favourable outcomes for stroke, bleeding, and systemic embolism (p<0.05) compared to VKA in the overall cohort (table 1). In the ACS group, DOAC was linked to a reduced risk of stroke and systemic embolism (p<0.05) with borderline reduction in bleeding (p=0.066). In the non-ACS group, DOAC was associated with a decreased risk of stroke and bleeding (p<0.05) but not systemic embolism (p=0.113). Across all groups, there were no disparities in relation to causes of mortality. <h3>Conclusion</h3> DOACs demonstrated better safety and efficacy outcomes when compared to VKAs in LVT treatment. DOAC utilisation within the ACS context was associated with a lower risk of embolic complications with a trend for reduced bleeding risks. <h3>Conflict of Interest</h3> none
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