Abstract Body (Do not enter title and authors here): Introduction: Atrial fibrillation (AF) is a common comorbidity in cancer patients, increasing their risk of stroke and mortality. Cancer patients are often excluded from anticoagulation and AF intervention trials due to the nature of their disease, and risk scores such as HAS-BLED, CHADS2/CHADS2-VASc often underpredict the high risk of AF and related complications for these patients.

Research Question: Does left atrial appendage occlusion (LAAO) reduce mortality, major bleeding events (MBE), and stroke in cancer patients with AF?

Methods: Using TriNetX, an international health research network with data from over 100 million patients, cancer patients with AF, with and without LAAO were identified between 2015 and 2022. Equal cohorts of 147 patients were created after propensity score matching for demographics, diabetes, hypertension, and heart failure. Measures of Association and Survival Analysis were conducted between 3-months and 5-years. The primary outcome was mortality. The secondary outcomes were MBE and stroke.

Results:
The study included 294 cancer patients with AF, with 147 having received LAAO. The risk of mortality at 3 months was 6.8% in the LAAO+ group compared to 15% in the LAAO- group (p-value= 0.025). At 6 months, the mortality risk was 8.8% in the LAAO+ group and 18.4% in the LAAO- group (p-value= 0.017). At 1 year, the mortality risk was 12.2% in the LAAO+ group and 23.8% in the LAAO- group (p-value=0.010). At 5 years, the mortality risk was 28.6% in the LAAO+ group and 49.7% in the LAAO- group (p-value<0.0001).

The MBE risk was 20.4% for the LAAO+ group and 32% for the LAAO- group at 3 months (p-value= 0.024). At 6 months, the MBE risk was 25.9% in the LAAO+ group and 40.1% in the LAAO- group (p-value=0.009). Although there was no significant difference in risk of MBE at 1 year and 5 years, survival was higher among the LAAO+ group than the LAAO- group (64.92% vs 52.76%; p-value= 0.038 at 1 year and 52.67% vs 39.23%; p-value=0.029 at 5 years). However, there was no difference between stroke risk or survival probability across all measured time points.

Conclusion: LAAO in cancer patients with AF was associated with significantly reduced mortality and major bleeding events over a 5-year period compared to those without LAAO. These findings suggest that LAAO may be a beneficial intervention for improving survival and reducing bleeding complications in cancer patients with AF.