Influence of diabetes mellitus on dapagliflozin response after transcatheter aortic valve replacement (TAVR): insights from the DAPA-TAVI trial

The DAPA-TAVI trial demonstrated that dapagliflozin reduced the composite of all-cause mortality or worsening heart failure (HF) at 1 year in patients undergoing transcatheter aortic valve replacement (TAVR) with prior HF. Whether the magnitude of this benefit differs according to diabetes mellitus (DM) status remains uncertain. This pre-specified subgroup analysis of the multicenter randomized DAPA-TAVI trial conducted at 39 centers in Spain, which enrolled 1222 patients with severe aortic stenosis undergoing TAVR with prior HF and at least one high-risk condition. Patients were stratified by the presence or absence of DM. The primary endpoint was a composite of all-cause mortality or worsening HF at 12 months. Secondary endpoints included the individual components of the primary endpoint, cardiovascular death, and safety outcomes. Cox proportional-hazards models adjusted for age, sex, coronary artery disease, baseline ejection fraction and baseline estimated glomerular filtration rate were used to estimate treatment effects. Among 1222 patients, 537 (43.9%) had DM. In patients with DM, dapagliflozin significantly reduced the primary endpoint compared with standard care (15.2% vs. 22.7%; HR 0.580; 95% CI 0.389–0.866; p = 0.008; number needed to treat NNT = 11), driven primarily by fewer worsening HF events. In patients without DM, the reduction was numerically lower and non-significant (15.0% vs. 18.0%; HR 0.814; 95% CI 0.560–1.183; p = 0.280; NNT = 32). Genital infections were more frequent with dapagliflozin in patients with DM, whereas symptomatic hypotension was more common in those without DM. No significant differences in serious adverse events were observed in either subgroup. No statistically significant interactions between DM status and treatment effect were observed for the primary or secondary endpoints. In this pre-specified subanalysis of the DAPA-TAVI trial, dapagliflozin significantly reduced the risk of death or worsening HF in patients with DM undergoing TAVR, with a favorable benefit–risk profile, whereas a more modest and non-significant effect was observed in non-DM patients. Although no statistically significant interaction according to diabetes status was observed, the apparently greater benefit among patients with DM warrants further investigation. Central Illustration: Distribution of patients by diabetes status in the DAPA-TAVI trial and impact of dapagliflozin on the primary outcome according to the presence or absence of diabetes.