Frailty usually marks the patients doctors worry about most after a heart procedure. A new analysis of a randomized trial suggests it may also point to who gains the most from treatment, which matters to older people facing a valve implant and to their families, with clear limits on what it shows.
On 16 October 2026 the Journal of the American Heart Association published a new analysis of DapaTAVI, a randomized trial run in Spain in people with severe aortic stenosis who had a transcatheter aortic valve implantation (TAVI), a valve replacement done through a blood vessel instead of open-heart surgery. At the start of the trial, 1,222 participants were scored on the FRAIL scale, which counts fatigue, weakness, difficulty walking, number of illnesses and weight loss: 47.2% were frail, 40.3% prefrail and 12.4% robust.
The outcome was the same as in the main trial: death from any cause or worsening heart failure within one year. It happened to 215 people (17.6%). Among frail patients, dapagliflozin was associated with a hazard ratio of 0.53 (95% CI 0.36–0.77), roughly half the risk of the combined outcome compared with standard care. In prefrail patients the hazard ratio was 1.01 (0.66–1.55), and in robust patients 1.26 (0.42–3.75). The test for a difference between these groups gave P = 0.021. The authors found no sign that frailty changed the drug's safety profile.
The trial behind the analysis
The main DapaTAVI results appeared in the New England Journal of Medicine in April 2025. The trial randomly assigned 1,257 people undergoing TAVI to dapagliflozin, a drug of the SGLT2 inhibitor class, or to standard care alone; there was no placebo. Everyone had a history of heart failure plus at least one of kidney dysfunction, diabetes or a weakened left ventricle. After exclusions, 1,222 were analysed. The combined outcome occurred in 15.0% with dapagliflozin and 20.1% with standard care (hazard ratio 0.72; 95% CI 0.55–0.95). Deaths from any cause were 7.8% and 8.9% (hazard ratio 0.87; 95% CI 0.59–1.28), a difference that could be due to chance. Worsening heart failure was 9.4% and 14.4%. Genital infections and low blood pressure were more common with the drug. The trial was sponsored by the Spanish Society of Cardiology and funded by the Instituto de Salud Carlos III and others.
Frailty marked both higher risk and a larger relative effect
Frailty was common in this group and, independently of other factors, it marked higher risk: compared with robust patients, the adjusted hazard ratio was 1.88 for prefrail and 2.29 for frail patients. In this post hoc analysis, the relative effect of the drug was also larger in frail patients: the people at the highest risk after the procedure appeared to gain the most. The result does not yet establish that a frailty score should decide who is offered the drug after TAVI.
What the result does not prove
This is a post hoc analysis: the trial was not designed to compare frailty groups, and splitting a trial into subgroups after the fact can produce differences by chance. The robust group was small, which is why its confidence interval is so wide. The outcome combines death with heart-failure events, and the main trial did not show a separate reduction in deaths, so the result cannot be read as "the drug extends life". Everyone in the trial already had heart failure and an additional risk factor, so it says nothing about people who are frail but have no heart disease. The abstract of the new analysis does not state its funding or conflicts of interest. Because this is a post hoc subgroup analysis, the finding needs confirmation before it can guide treatment decisions.
If you or a relative are preparing for TAVI or have recently had it, frailty and this class of drug are a reasonable topic to discuss with your cardiologist.
This material is for information only and does not replace a consultation with a doctor. Nothing in it is a recommendation to start, stop or change treatment.
Sources
Gonzalez-Manzanares R, et al. Dapagliflozin After Transcatheter Aortic Valve Implantation According to Frailty in DapaTAVI Trial. J Am Heart Assoc. 2026. PMID 42885795
Raposeiras-Roubin S, et al. Dapagliflozin in Patients Undergoing Transcatheter Aortic-Valve Implantation. N Engl J Med. 2025. PMID 40162639
Dapagliflozin After Transcatheter Aortic Valve Implantation (DapaTAVI). ClinicalTrials.gov. NCT04696185
Articles in this section are educational and are not medical advice, a diagnosis, or a prescription. Consult a qualified professional before acting on anything you read here.
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