Role of GLP1a drugs after TAVI: insights from the MOTIVE registry

Abstract

GLP-1 receptor agonists (GLP-1a) are a novel class of cardiometabolic drugs that have been shown to reduce the risk of major adverse cardiovascular events (MACE) and cardiovascular mortality in patients with type 2 diabetes, overweight, or obesity. Improved outcomes have also been reported in patients undergoing transcatheter aortic valve implantation (TAVI) treated with the SGLT2 inhibitor dapagliflozin in the recent DAPA-TAVI trial. Whether GLP-1a could provide similar benefits in patients with valvular heart disease, such as aortic stenosis, remains unknown. We retrospectively analyzed TAVI patients enrolled in the monocentric MOTIVE registry at a hospital, between 2015 and 2025. Patients were stratified according to whether they were prescribed GLP-1a at discharge. Outcomes were compared between groups using both propensity score matching (PSM) and inverse probability weighting (IPW). Cox regression was applied to assess the following endpoints: the composite of all-cause death and hospitalization for heart failure (HHF), all-cause death, cardiovascular death, HHF, and stroke. A total of 803 TAVI patients were included, of whom 45 (5.6%) received GLP-1a at discharge. The mean age was 81.1 ± 6.2 years, with a slight female predominance (403, 50.2%). Mean left ventricular ejection fraction was 56.5 ± 11.3%, and mean transvalvular gradient was 42.1 ± 12.3 mmHg. A self-expandable valve was implanted in 509 patients (63.4%), most commonly the Evolut R/PRO/PRO+ (362, 45.0%). Baseline, echocardiographic, and procedural characteristics were balanced between groups, except for diabetes, which was markedly more prevalent in the GLP-1a group (43/45, 95.5%). After a median follow-up of 363.5 days (IQR 224–592), in the IPW-adjusted cohort, GLP-1a prescription at discharge was associated with a lower risk of the composite endpoint of all-cause death or HHF (HR 0.34, 95% CI 0.17–0.68, p = 0.01), primarily driven by a reduction in HHF (HR 0.30, 95% CI 0.15–0.56, p = 0.008). No significant differences were observed in cardiovascular death or stroke during long-term follow-up. In this contemporary cohort of TAVI patients, GLP-1a prescription at discharge was associated with a marked reduction in the composite of all-cause death and HHF, mainly due to fewer heart failure hospitalizations. Given the observational and monocentric nature of this study, these findings should be considered hypothesis-generating. Larger multicenter registries and randomized controlled trials are warranted to confirm these preliminary results.