Role of Glp1 Agonist After Tavi: Insights From Motive Registry

Introduction GLP–1a are a novel class of cardiometabolic drugs that have been shown to reduce the risk of MACE and cardiovascular mortality in patients with type 2 diabetes, overweight, or obesity. Improved outcomes have also been reported in patients undergoing 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. Methods We retrospectively analysed TAVI patients enrolled in the monocentric MOTIVE registry at Molinette Hospital, Turin, 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. Results 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. Conclusions In this cohort, 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.