Abstract Body (Do not enter title and authors here):
Background
Patients undergoing percutaneous left atrial appendage occlusion (LAAO) for atrial fibrillation often have comorbid diabetes and obesity. GLP-1 receptor agonists provide benefit in patients with these comorbid conditions. The impact of GLP-1 receptor agonists on outcomes in patients undergoing LAAO occlusion has not been previously assessed.

Hypothesis
GLP-1 receptor agonists may contribute to improved outcomes in patients undergoing percutaneous LAAO compared to those not receiving GLP-1 therapy.

Methods
A retrospective analysis using the TriNetX network identified adults who underwent LAAO over the past 20 years. Patients were grouped as GLP-1 receptor agonist users or non-users within three months before or any time after the procedure. The primary outcome was a three-component MACE, comprising all-cause mortality, stroke, and major bleeding. Secondary outcomes included myocardial infarction and heart failure exacerbation. These were assessed using odds ratios (ORs), with statistical significance at p < 0.05. Kaplan–Meier curves and log-rank tests were used for time-to-event survival analysis.

Results
A total of 4,382 patients (2,191 in each group) were included after propensity score matching. The mean age was 71.6 years, with 57% identified as male. At one-year follow-up, patients in the GLP-1 group exhibited significantly lower odds of MACE (OR: 0.64; 95% CI: 0.56–0.73; p < 0.001). Kaplan–Meier analysis for MACE supported these findings, showing a hazard ratio of 0.66 (95% CI: 0.59–0.74) with a log-rank p-value of <0.001 (Figure 1). GLP-1 users also had significantly reduced odds of all-cause mortality (OR: 0.42; 95% CI: 0.31–0.56; p < 0.001), major bleeding (OR: 0.64; 95% CI: 0.54–0.74; p < 0.001), myocardial infarction (OR: 0.78; 95% CI: 0.62-0.97; p=0.025), and heart failure exacerbation (OR: 0.65; 95% CI: 0.56–0.77; p < 0.001). However, no significant differences were observed in the odds of stroke (OR: 0.87; 95% CI: 0.70–1.09; p=0.220) between the two groups (Figure 2).

Conclusions
GLP-1 receptor agonist therapy was associated with a significantly lower risk of MACE, primarily driven by reductions in mortality and bleeding. These findings suggest a beneficial role for GLP-1 receptor agonists in patients undergoing percutaneous LAAO.