Abstract Body (Do not enter title and authors here): Introduction: Recent studies have demonstrated the potential cardiac benefits of GLP1 receptor agonists (GLP1-RA). Specifically, these drugs have been shown to improve patient symptoms and reduce both mortality and heart failure hospitalizations (HFH) in patients with heart failure with preserved ejection fraction. However, little is known about their effects on hypertrophic cardiomyopathy (HCM). In this retrospective study, we analyze a cohort of patients with HCM prescribed GLP1-RAs and assess their relative risk of all-cause mortality, HFH, major adverse cardiac events (MACE), and myocardial infarction (MI).

Methods: All Icahn Mount Sinai Health System patients were searched using TriNetX from 1/1/2005-6/1/2025. Patients with HCM, BMI >25, and age >18 years were included. Patients who did not meet the inclusion criteria or who had any of the outcomes of interest prior to indexing were excluded. The control cohort was composed of included patients who were not prescribed a GLP1-RA. The cohorts were propensity matched and balanced for baseline characteristics (i.e. BMI, hypertension, age, sex, etc.). Statistical analysis was performed via Cox regression using the built-in TriNetX calculator. Outcomes are reported as risk ratios (HR) and 95% confidence intervals (CI).

Results: A total of 2,940 patients with HCM were included in the analysis after propensity matching (GLP1 n=;1470 no GLP1 n=1,470). Baseline characteristics of the cohorts did not differ significantly between the groups. There was a significant 30.5% reduction in the risk of all-cause mortality (HR 0.695, 95% CI 0.552-0.874, P = 0.0019), 19.3% reduction in risk of MI (HR 0.807, 95% CI 0.651-0.999, P = 0.0494), and 24.1% reduction in risk of MACE (HR 0.759, 95% CI 0.661-0.871, P<0.0001) for HCM patients prescribed GLP1-RAs as compared to those who were not. There was a small, non-significant decrease in the risk of HFH in the GLP1-RA cohort (HR 0.968, 95% CI 0.867-1.081, P = 0.5642).

Conclusion: In the present analysis of a large, real-life cohort, GLP1-RAs were shown to reduce the risk of adverse cardiovascular events and all-cause mortality in patients with HCM. Surprisingly, however, there were no significant effects on HFH. Further research, including prospective randomized-controlled trials, is needed to better qualify the effects of GLP1-RAs in HCM and to elucidate the underlying mechanism of the beneficial effects that were seen in this retrospective study.