Dapagliflozin Shows Promise After TAVI in Elderly Aortic Stenosis Patients

Aortic stenosis is a condition that causes the aortic valve, one of your heart valves that works to carry blood from your heart to the body, to become narrowed or blocked. This narrowing of heart valves restricts blood flow, thereby forcing your heart to do some “hard work” to pump blood through it, which eventually results in complications like a heart attack. This condition is the most common valvular heart disease and affects the elderly population the most.

So, if you have aortic stenosis, what's next? The standard of care is a minimally invasive procedure called Transcatheter Aortic Valve Implantation (TAVI) that replaces the damaged valve without the need for open-heart surgery. However, some patients may not recover as expected from this treatment. Many individuals continue to be at high risk of being admitted to the hospital due to heart failure, sadly, most resulting in death, leaving doctors and researchers to explore a solution for this.

An Unexpected Ally: A Diabetes Drug

A class of medications known as sodium–glucose cotransporter 2 (SGLT2) inhibitors, which were originally developed to treat type 2 diabetes by lowering blood sugar, also has the additional beneficial effect of protecting your heart and kidneys. Even high-risk heart patients who took this drug were reported to have fewer hospital stays for heart failure and even lived longer. However, this drug didn't have strong evidence regarding its efficacy on heart failure due to reversible conditions, like aortic stenosis, especially in the elderly population. This made a group of researchers in Spain wonder if this drug can help those who are recovering from heart valve replacement, even if they don’t have diabetes.

That’s where the DapaTAVI trial comes in.

What is the DapaTAVI trial?

This randomised open-blinded end-point (PROBE) controlled trial was conducted in 39 centres across Spain from January 2021 through December 2023. The trial, conducted by Dr Raposeiras-Roubín and the team, investigated the effect of dapagliflozin (Farxiga; AstraZeneca), a type of SGLT2 inhibitor, in older patients (mean age 82.4 years; 49.4% women) undergoing TAVI for severe aortic stenosis. In order to be eligible for the research, patients were required to have undergone a TAVI procedure and have at least one additional medical condition, such as a history of heart failure, diabetes, renal insufficiency, or poor cardiac function (left ventricular ejection fraction of ≤40%). People who experienced health issues due to dapagliflozin, those who were already taking similar medications, and those with low blood pressure (below 100/50 mmHg), serious kidney problems (very low kidney filtration rate), or a history of recurrent urinary tract infections were excluded from the study.

Patients were randomly assigned to receive treatment within 14 days of discharge from the hospital following TAVI. Among 1,222 patients recruited for the trial, half of them (n = 605) were randomly given dapagliflozin (at an oral dose of 10 mg once daily) along with standard care, while the other half (n = 617) received only standard care. The study lasted a year, with results being tracked at 3 and 12 months.

The main aim was to see whether the medication could lower the risk of death or worsening heart failure, which would require another visit to the hospital or immediate care. Researchers also monitored the number of hospital visits they had and side effects like infections and low blood pressure.

Are the findings promising?

Yes, they are! Those patients who received treatment with dapagliflozin had better health outcomes. Only a few people in this group had worsening of heart failure and death compared to people who received only standard care (15% vs. 20%, hazard ratio [HR], 0.72; p = 0.02). Moreover, compared to the patients in the standard-care group, these people also had fewer hospitalisations due to heart failure (7.4% vs. 10.7%; subhazard ratio, 0.68; 95% CI, 0.46 to 0.99) and fewer urgent hospital visits requiring intravenous diuretic therapy (2.8% vs. 6%; subhazard ratio, 0.46; 95% CI, 0.26 to 0.82).

Then what about the safety of this drug? Even though there were no major side effects, patients who received dapagliflozin, compared to those who didn't take it, experienced more side effects like genital infections (1.8% vs. 0.5%; p = 0.03) and low blood pressure (6.6% vs. 3.6%; p = 0.01).

Why it matters

These promising findings of the trial give hope for patients with aortic stenosis who have undergone TAVI and are at high risk of heart failure. For them, adding dapagliflozin to the standard treatment could potentially reduce the risk of death or worsening heart failure. Moreover, since the study was conducted in the elderly population, the findings that this drug is safe and beneficial for them are particularly significant because, despite their potential health advantages, doctors often do not recommend SGLT2 inhibitors to older adults.

The study also found that dapagliflozin was equally effective in women and men, and it showed benefits irrespective of kidney function or diabetes status. However, given the study's shortcomings, like its open-label design, limited safety data, and the fact that the study was carried out only in Spain, it further necessitates more extensive, diverse, and long-term research in order to validate the findings.

The trial was presented during the American College of Cardiology (ACC) 2025 Late-Breaking Clinical Trial session in Chicago and published in the New England Journal of Medicine.

Source

Raposeiras-Roubin S, Amat-Santos IJ, Rossello X, González Ferreiro R, González Bermúdez I, Lopez Otero D, et al. Dapagliflozin in Patients Undergoing Transcatheter Aortic-Valve Implantation. N Engl J Med [Internet]. 2025 [cited 2025 May 3]; 392(14):1396–405. Available from: http://www.nejm.org/doi/10.1056/NEJMoa2500366.

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