medwireNews: The reported cardiac benefits of the sodium-glucose cotransporter (SGLT)2 inhibitor dapagliflozin extend to older people with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI), show the results of the DapaTAVI trial.
At 1 year, 15.0% of 605 people treated with dapagliflozin versus 20.1% of 617 who received standard care after TAVI experienced the primary composite endpoint of all-cause death or worsening heart failure (HF). The latter was defined as either HF hospitalization or the need for an urgent HF visit requiring intravenous diuretics.
This equated to a significant 28% relative risk reduction in the occurrence of death or worsening HF favoring the use of dapagliflozin, report Sergio Raposeiras‑Roubin (Hospital Álvaro Cunqueiro, Pontevedra, Spain) and co-authors in The New England Journal of Medicine.
The findings – which were published to coincide with their presentation at the American College of Cardiology annual meeting (ACC.25) in Chicago, Illinois, USA – suggest that the superior reduction in the primary endpoint with dapagliflozin was driven by its effect on HF. The rate of HF worsening was significantly lower in this group than the standard care group (9.4 vs 14.4%), as were the rates of HF hospitalization (7.4 vs 10.7%) and urgent HF visits (2.8 vs 6.0%).
By contrast, the rates of death from any cause were numerically lower in the dapagliflozin group compared with the standard care group, but not significantly so (7.8 vs 8.9%).
Participants in the trial had severe aortic stenosis requiring TAVI and prior aortic stenosis-related HF either requiring hospitalization or urgent care. They also met at least one of the following additional criteria: moderate renal insufficiency (estimated glomerular filtration rate [eGFR] of 25–75 mL/min per 1.73m²); diabetes mellitus; or left ventricular systolic dysfunction (ejection fraction ≤40%).
The participants were randomly assigned to receive treatment a median of 2 days after TAVI, with those allocated to the dapagliflozin group receiving a 10 mg once-daily dose. Clinical outcomes were assessed at 3 and 12 months by telephone interviews and review of medical records and national vital statistics registries.
The mean age of the participants was 82.4 years and 50.6% were men. Additionally, 43.9% had diabetes, 17.0% had left ventricular systolic dysfunction, and 88.6% had moderate renal dysfunction (mean eGFR=56.2 mL/min per 1.73m²).
Secondary outcomes that occurred significantly less frequently in the dapagliflozin than the standard care group included any hospitalization for HF or death from cardiovascular causes (10.1 vs 13.8%) and total number of recurrent HF hospitalizations or cardiovascular deaths (79 vs 121). The subhazard ratios both favored dapagliflozin treatment over standard care, with significant respective relative risk reductions of 29% and 33%.
Rates of death from cardiovascular causes were numerically lower with dapagliflozin, at 4.5% versus 5.3% with standard care, but the difference was not statistically significant.
Adverse events (AEs) known to occur with dapagliflozin were seen more frequently in this group than the standard care group, including genital infections (15.5 vs 11.5%) and hypotension (6.6 vs 3.6%). Other AEs, such as bacteremia, syncope, major hypoglycemia, nontraumatic amputation, and cancer, did not differ significantly between the groups. No cases of diabetic ketoacidosis or necrotizing fasciitis were reported in either group.
“Our current findings extend the evidence from previous trials of SGLT2 inhibitors,” say the DapaTAVI investigators, referencing the DapaHF, DELIVER, and DECLARE-TIMI 58 trials.
The study’s limitations include its “pragmatic and open-label” design and being conducted exclusively at 39 Spanish centers. While data on race and ethnicity were not collected, the investigators expect that 90% of the participants were White.
A study strength, however, is the inclusion of older patients undergoing aortic value replacement, who are often not included in clinical studies.
The investigators conclude: “Our results appear to confirm that SGLT2 inhibitors are safe in older patients and are associated with clinical benefits, which is important given the low frequency of prescriptions for SGLT2 inhibitors among older patients.”
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N Engl J Med 2025; doi:10.1056/NEJMoa2500366
ACC.25; Chicago, Illinois, USA: 29–31 March
