Abstract 4371398: Glucagon Receptor Agonist Impact on Cardiac Amyloidosis. A Retrospective Propensity Matched Analysis

Introduction: Cardiac amyloidosis is a complex and progressive infiltrative cardiomyopathy associated with high morbidity and mortality. Recent studies have raised interest in the cardiometabolic benefits of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) agonists. This study aimed to evaluate the impact of GLP/GIP therapy on key cardiovascular outcomes in patients with cardiac amyloidosis using real-world data. Methods: A retrospective cohort analysis was conducted using the TriNetX global federated research network. Two cohorts were identified: patients with cardiac amyloidosis treated with GLP/GIP agents (n = 6,838) and those not exposed to such agents (n = 93,367). Propensity score matching yielded two balanced groups (n = 8,083 each), with outcomes assessed between 90 and 365 days following the index event. Patients with prior occurrences of each outcome were excluded from the respective analyses. The primary outcomes included all-cause mortality, ventricular fibrillation (VFib), ventricular tachycardia (VTach), atrial fibrillation (Afib), and heart failure (HF). Risk ratios (RR) were computed to compare the incidence of each outcome between groups. Results: GLP/GIP agents were associated with a consistently lower risk of adverse outcomes across all endpoints. The mortality risk was reduced by more than half in the treatment group compared to controls (RR 0.459, 95% CI: 0.384–0.548, p < 0.001). Similarly, patients receiving GLP/GIP therapy had lower risks of VFib (RR 0.428, 95% CI: 0.243–0.754, p = 0.002), VTach (RR 0.728, 95% CI: 0.566–0.936, p = 0.013), Afib (RR 0.664, 95% CI: 0.521–0.848, p = 0.001), and HF (RR 0.587, 95% CI: 0.463–0.745, p < 0.001). Kaplan-Meier survival analyses corroborated these findings, showing improved event-free survival across all GLP/GIP group outcomes. Conclusion: In this large, real-world cohort of patients with cardiac amyloidosis, treatment with GLP/GIP agents was associated with significantly lower risks of mortality, arrhythmias, and heart failure. These findings suggest a potential cardioprotective effect of GLP/GIP therapy in a high-risk population and the need for prospective studies to validate these observations and guide clinical practice.