1257 - Timing of GLP-1 Receptor Agonist Initiation and Cardiovascular Events in Men Receiving Androgen Receptor Pathway Inhibitors
Presenter(s)
K. M. Atkins1, N. Chakravarty2, M. Oorloff1, G. Grigsby2, I. Khan3, M. Kamrava4, A. Nikolova5, A. Karlstaedt2, C. Ramin6, and L. K. Ballas1; 1Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, 2Cedars-Sinai Medical Center, Los Angeles, CA, 3Cedars Sinai Medical Center, Los Angeles, CA, United States, 4Cedars Sinai, Los Angeles, CA, 5Department of Cardiology, Cedars-Sinai Medical Center, Los Angeles, CA, 6Department of Biomedical Sciences, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA
Purpose/Objective(s): Cardiovascular disease is a major cause of morbidity and mortality among men with prostate cancer (PC), and androgen receptor pathway inhibitors (ARPIs) are associated with increased cardiovascular risk. GLP-1 receptor agonists (GLP-1RAs) reduce cardiovascular events in non-cancer populations, but their role in patients receiving ARPIs is unclear. We evaluated whether GLP-1RA use and timing relative to ARPI initiation were associated with cardiovascular events.
Materials/Methods: Retrospective analysis of 120 men with PC treated with ARPIs between 2015-2025 with GLP-1RA exposure. GLP-1RA use was categorized by timing relative to ARPI initiation (pre- vs post-ARPI). Composite cardiovascular events after ARPI initiation were evaluated, including strict major adverse cardiac events (MACE; myocardial infarction, unstable angina, heart failure, coronary revascularization, ischemic stroke, and cardiovascular death) and any common terminology criteria for adverse events (CTCAE) grade =2 cardiovascular event (CE; including arrhythmia and valvular heart disease). Cumulative incidences were estimated and Fine-Gray regressions were performed (accounting for non-cardiac death as a competing risk).
Results: Median follow-up was 2.3 years (interquartile range [IQR] 1.3–3.7). Median age was 72 years (IQR 66–78); 51% had metastatic disease, 62% were on androgen deprivation therapy (ADT) prior to ARPI. Cardiovascular comorbidities were common, including hypertension (84%), hyperlipidemia (82%), diabetes (70%), and atherosclerotic cardiovascular disease (ASCVD; 45%), though only 59% of patients with ASCVD were on statin therapy. Overall, 55% initiated GLP-1RA therapy prior to ARPI and 45% after ARPI initiation. Four patients experienced MACE (3 coronary revascularization, 1 ischemic stroke), and 25 experienced at least one grade =2 CE, most commonly arrhythmia and thromboembolic events. The 2-year cumulative incidence of MACE and grade =2 CE was 2% and 8%, respectively. Adjusting for cardiovascular risk, statin use, GLP-1RA duration, and pre-ARPI ADT use, GLP-1RA use prior to ARPI initiation was associated with reduced risk of grade =2 CE (subdistribution hazard ratio 0.26, 95% confidence interval [CI] 0.08-0.91; p=0.036). Corresponding 2-year grade =2 CE rates were 11% with pre-ARPI GLP-1RA vs 22% with post-ARPI initiation (p=0.040).
Conclusion: Men with PC receiving ARPI therapy have substantial baseline cardiovascular risk, with notable statin underutilization despite high ASCVD prevalence. GLP-1RA use prior to ARPI initiation was associated with reduced risk of symptomatic cardiac events, suggesting that earlier cardiometabolic optimization may influence cardiovascular outcomes. These findings support investigation of early GLP-1RA initiation as a potential cardiovascular risk mitigation strategy during ARPI therapy.