Outcomes associated with left atrial appendage occlusion in patients with cancer-associated atrial fibrillation: a real-world propensity-matched analysis

Atrial fibrillation (AF) is a common comorbidity in cancer patients, increasing their risk of stroke and mortality. Cancer patients are often excluded from risk stratification models such as HAS-BLED and CHA₂DS₂-VASc, which may underestimate AF-related risks. Additionally, oral anticoagulation in this population increases bleeding risk. This study evaluated the role of left atrial appendage occlusion (LAAO) in cancer patients with AF. TriNetX, a global federated health research network, was used to identify cancer patients with AF, with and without LAAO, from 2015 to 2023. Propensity score matching (1:1) was performed for age, race, sex, comorbidities, and medication use, generating two equal cohorts of 1,228 patients. The primary endpoint was major bleeding; the secondary endpoints were ischemic stroke and all-cause mortality. Secondary analyses compared LAAO with direct oral anticoagulants (DOACs) and warfarin. Among 2,456 matched AF patients, 1,228 underwent LAAO. LAAO was correlated with significantly lower major bleeding at 3 months (26.4% vs. 33.0%, p < 0.001), with similar trends at 1 year (p = 0.019) and 3 years (p = 0.005). Compared to warfarin, LAAO had lower major bleeding (p = 0.006); rates were similar to DOACs (p = 0.356). Ischemic stroke rates were not significantly different between groups at any time point. LAAO recipients exhibited lower mortality at 3 months (3.6% vs. 15.3%, p < 0.0001), 1 year (11.1% vs. 29.7%, p < 0.001), and 3 years (23.5% vs. 36.9%, p < 0.001). Mortality was also lower in LAAO recipients compared with DOAC (p < 0.001) and warfarin (p < 0.001) groups. In adjusted Cox models, LAAO remained associated with significantly lower mortality (adjusted HR 0.63), while adjusted risks of major bleeding and ischemic stroke did not differ between groups. In cancer patients with AF, LAAO was correlated with lower major bleeding and mortality in matched analyses, while stroke rates were similar. In adjusted Cox models, LAAO remained correlated with lower mortality, whereas bleeding and stroke risks were not significantly different. These findings should be interpreted in the context of real-world treatment selection and the absence of granular data on cancer stage, disease activity, timing of LAAO, and cause-specific mortality.