Abstract Body: Introduction: This study investigated the efficacy of direct oral anticoagulants (DOACs) versus warfarin in ischemic stroke (IS) patients with reduced left ventricular ejection fraction (LVEF ≤30%), examining outcomes both with and without left ventricular thrombus (LVT).

Methods: A multicenter retrospective study was conducted across 15 sites using an intent-to-treat framework. The study included consecutive patients with LVEF ≤30% following an IS, excluding those on mixed antithrombotic regimens prior to any outcome event. The primary outcome combined new IS occurrence and mortality at last follow-up given low prevalence of new IS events. Similarly, we used a composite outcome for bleeding events, encompassing intracranial hemorrhage and major extracranial bleeding. In all cases, we used inverse propensity-score weighted logistic regression, adjusting for demographics, comorbidities, and stroke severity. For patients without LVT, we also adjusted for concurrent antiplatelet therapy use.

Results: Of 771 screened patients, 370 met inclusion criteria, with 264 (71.4%) receiving DOACs and 106 (28.6%) receiving warfarin. The cohort included 295 patients without LVT and 75 with LVT. Overall, new IS occurred in 3.8% (4/106) of warfarin patients and 6.4% (17/264) of DOAC patients. Deaths occurred in 22.6% (24/106) of warfarin patients versus 23.1% (61/266) of DOAC patients. In patients without LVT, DOAC use proved non-inferior for the primary outcome (adjusted odds ratio [aOR] 0.91, 95% confidence interval [CI] 0.52-1.58), mortality (aOR 0.78, 95% CI 0.43-1.38), bleeding (aOR 1.52, 95% CI 0.71-3.26), and major bleeding (aOR 0.96, 95% CI 0.10-9.03). Among patients with LVT, DOAC demonstrated non-inferiority for the primary outcome (aOR 0.47, 95% CI 0.13-1.67) and bleeding (aOR 2.90, 95% CI 0.70-12.06), while showing significant benefits in mortality (aOR 0.18, 95% CI 0.03-0.88) and major bleeding (aOR 0.77, 95% CI 0.67-0.87) compared to warfarin. Interaction analyses revealed DOAC use had an enhanced protective effect against mortality as LVEF decreased (aOR 1.28, p=0.02) among LVT patients.

Conclusions: DOACs demonstrated non-inferiority to warfarin in IS patients with LVEF ≤30% without LVT across all outcomes. In patients with LVT, DOACs showed superior outcomes in mortality and major bleeding. These findings suggest promising potential for DOACs in secondary prevention for specific IS populations, though further research is warranted to confirm these benefits.