ACC 2025: Dapagliflozin Found Safe, Effective in Older Adults With Heart Failure Undergoing Valve Replacement

In the first trial of a sodium-glucose cotransporter-2 (SGLT2) inhibitor for valvular disease, investigators found that patients with heart failure who took dapagliflozin (Farxiga; AstraZeneca) after undergoing transcatheter aortic valve replacement (TAVR) were significantly less likely to die or experience worsening heart failure at 1 year compared with patients who did not take the medication.¹

Image credit: luchschenF | stock.adobe.com

According to systematic review data published in 2021, SGLT2 inhibitors have been shown to decrease cardiovascular death and heart failure hospitalizations in patients with heart failure. Among the 15 randomized trials and 20,241 patients included in the meta-analysis, 10,594 received SGLT2 inhibitors. Among those, all-cause mortality (HR 0.86; 95% CI 0.79-0.94; p=0.0007) and cardiovascular mortality (HR 0.86; 95% CI 0.78-0.96; p=0.006) were significantly lower compared with patients who received placebo. Furthermore, the composite of cardiovascular mortality, heart failure hospitalizations, or urgent visits for heart failure was significantly reduced with SGLT2 inhibitors in all of the following subgroups: male, female, age younger than 65, age 65 years or older, Black race, White race, estimated glomerular filtration rate (eGFR) less than 60, eGFR of 60 or greater, New York Heart Association (NYHA) class 2, NYHA class 3 or greater, and heart failure with preserved ejection fraction.²

Despite this substantial body of data, SGLT2 inhibitors have not previously been tested in those undergoing TAVR, also known as transcatheter aortic valve implantation (TAVI). TAVR is a less invasive option than open heart surgery for patients with heart failure and valvular heart disease. The new trial, DapaTAVI, was presented at the American College of Cardiology 2025 Scientific Session and is the first to assess the use of SGLT2 inhibitors in individuals undergoing the procedure.^3,4

“Previous trials have provided evidence for SGLT2 inhibitors in patients with a variety of other conditions but have excluded patients with valvular heart disease,” said Sergio Raposeiras-Roubin, MD, the DapaTAVI study’s first author. “Based on our study, if you have a patient undergoing TAVI who is at risk of heart failure, it is important to treat them with dapagliflozin or another SGLT2 inhibitor. These are safe drugs and have a lot of benefit.”

The DapaTAVI trial enrolled 1257 patients undergoing TAVR at 39 Spanish hospitals. Participants had an average age of 82 years, and half were women. All participants had previously been hospitalized for heart failure and had severe aortic stenosis as well as at least 1 other condition that put them at high risk of poor health outcomes, such as diabetes, poor kidney function, or a low left ventricular ejection fraction.⁴

Half of the participants were randomly assigned to daily dapagliflozin starting within 2 weeks after TAVR, and half did not take dapagliflozin. At 1 year, the rate of the study’s primary end point, a composite of all-cause death or worsening heart failure, was 28% lower in patients taking dapagliflozin. This statistically significant improvement was attributed to a 37% reduction in worsening heart failure among those taking dapagliflozin. The 2 study groups did not see a significant difference in the rate of all-cause death.³

The rate of adverse events was relatively high in both arms due to advanced age and comorbidities. Participants in the dapagliflozin arm reported many of the same adverse effects found in previous clinical trials, including low blood pressure. There was no difference between study groups in the rate of urinary tract infections, which are also associated with SGLT2 inhibitors. Individuals in the dapagliflozin arm did see a higher rate of genital infection.⁴

“We found that these drugs are safe even in our elderly population, who are usually excluded from clinical trials,” Raposeiras-Roubin said. “It is important to have evidence in this group of patients; it is good for science and good for physicians to have an independent trial to demonstrate that the [beneficial] effect of SGLT2 inhibitors is also consistent in subgroups of patients in whom we didn’t have evidence until now.”

The findings were consistent across subgroups of age, sex, kidney function, and diabetes status. The investigators plan to further study whether there were any differences by left ventricle ejection fraction, and additional sub-studies are underway to assess quality of life outcomes.

REFERENCES

1. Raposeiras-Roubin S. Dapagliflozin safe and effective in elderly patients with heart failure undergoing valve replacement. Presented at: American College of Cardiology 2025 Scientific Session. Chicago, IL; March 29, 2025.

2. Cardoso R, Graffunder FP, Ternes CMP, et al. SGLT2 inhibitors decrease cardiovascular death and heart failure hospitalizations in patients with heart failure: a systematic review and meta-analysis. EClinicalMedicine. 2021;36:100933. doi:10.1016/j.eclinm.2021.100933

3. Dapagliflozin safe and effective in elderly patients with heart failure undergoing valve replacement. News release. American College of Cardiology. March 29, 2025. Accessed March 29, 2025.

4. Raposeiras-Roubin S, Amat-Santos IJ, Rossello X, et al. Dapagliflozin in patients undergoing transcatheter aortic-valve implantation. N Engl J Med. 2025; ePub online.