GLP-1 receptor agonist treatment and cardiovascular outcomes following aortic valve replacement: a nationwide observational study

Abstract Background GLP-1 receptor agonists reduce major adverse cardiovascular events among patients with diabetes, overweight, and obesity. Whether these benefits extend to patients undergoing aortic valve replacement (AVR) for severe aortic stenosis (AS) remains unknown. Thus, we investigated the association between GLP-1 receptor agonist treatment and cardiovascular outcomes after AVR. Methods Nationwide population-based cohort study including consecutive patients with severe AS undergoing TAVI or SAVR in Western Denmark between January, 2016 and April, 2022. Patients were followed until death, emigration, crossover, or end of follow up on May 12, 2026. Propensity score-matching was performed to balance confounding. The primary outcome was a composite of all-cause mortality, heart failure hospitalization, or aortic valve reoperation. Secondary outcomes included all-cause mortality, heart failure hospitalization, aortic valve reoperation, with analyses accounting for the competing risk of death. Results Among 5259 eligible patients undergoing AVR, 292 propensity score-matched patients were included in the final analyses. During a mean follow up of 4.8±2.4 years, GLP-1 receptor agonist treatment was associated with a lower risk of the primary composite outcome compared with controls (HR 0.69, 95%CI 0.50-0.96, p=0.029). GLP-1 receptor agonist treatment was also associated with lower risk of all-cause mortality (HR 0.66, 95%CI 0.46-0.95, p=0.025). In competing risk analyses accounting for death, lower risks were observed for heart failure hospitalization (HR 0.67, 95%CI 0.48-0.93, p=0.018), and aortic valve reoperation (HR 0.69, 95%CI 0.49-0.98, p=0.037). Conclusion Treatment with GLP-1 receptor agonists was associated with lower risk of cardiovascular outcomes including mortality following AVR among patients with severe AS.