The SGLT2 inhibitor dapagliflozin was superior to standard care alone in decreasing rates of all-cause mortality or worsening heart failure (HF) in older adults with aortic stenosis undergoing TAVI, resulting in a 28% relative risk reduction, according to results from the DAPA-TAVI study presented during a Late-Breaking Clinical Trial session during ACC.25 in Chicago and simultaneously published in the NEJM.

In the first trial of an SGLT2 inhibitor for valvular disease, DAPA-TAVI was conducted at 39 centers across Spain, from January 2021 to December 2023. Researchers randomized 1,222 patients (median age 82.4 years, 49.4% women) with severe aortic stenosis to either 10 mg of dapagliflozin once daily (n=605) or standard care (n=617) within 14 days of hospital discharge after TAVI. All patients had HF plus at least one other condition that placed them at high risk, moderate renal insufficiency (in 88.6%), diabetes (in 43.9%) or a LVEF ≤40% (17%). Of the patients, 72% were older than 80 and 7% older than 90 years. More patients in the dapagliflozin group than the standard care group had coronary artery disease and a higher NT-proBNP level, otherwise baseline characteristics were well balanced.

Results showed that at one year the composite primary outcome of all-cause death or worsening HF occurred in 91 patients (15.0%) in the dapagliflozin group and 124 patients (20.1%) in the standard care group (hazard ratio [HR], 0.72; p=0.02). This was attributable to a 37% reduction in worsening HF in the dapagliflozin arm (9.4% vs. 14.4% in the standard care group). Death from any cause occurred in 7.8% of the dapagliflozin group and 8.9% in the standard care group (HR, 0.87).

The rate of adverse events in both groups was high due to advanced age and comorbidities. Genital infection (1.8% vs. 0.5%, p=0.03) and hypotension (6.6% vs. 3.6%; p=0.01) were significantly more common in the dapagliflozin group than the standard care group.

The results were consistent across subgroups in terms of age, sex, kidney function and diabetes status. The researchers plan to further study whether there were any differences by left ventricle ejection fraction. Additional substudies are underway to assess quality of life outcomes.

In an accompanying editorial comment, Ori Ben-Yehuda, MD, FACC, noted there was greater benefit for patients with atrial fibrillation and older patients, important considering that, "given the pervasive assumption that the mechanical problem, namely aortic stenosis, had been solved with the TAVI procedure, SGLT2 inhibitors have been under-prescribed in this population, particularly among older patients."

"We found that these drugs are safe even in our elderly population, who are usually excluded from clinical trials," said Sergio Raposeiras-Roubin, PhD, MD, the study's first author "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."