No Additional Gain in Quality of Life With Dapagliflozin on Top of TAVI

BELGRADE, Serbia—Dapagliflozin (Farxiga; AstraZeneca) does not further improve quality of life in older patients with aortic stenosis and a history of heart failure (HF) undergoing TAVI despite reducing the risk of all-cause mortality and worsening HF, a substudy of the DapaTAVI trial shows.

Clara Bonanad Lozano, MD, PhD (University Clinical Hospital of Valencia, Spain), reported the results here at the European Society of Cardiology’s Heart Failure 2025 congress.

In TAVI-treated patients randomized to dapagliflozin or standard care, Kansas City Cardiomyopathy Questionnaire (KCCQ) scores jumped more than 35 points by 3 months after the procedure, with results sustained through 1 year, but the KCCQ scores did not significantly differ between groups. However, significantly more patients had NYHA class I symptoms at 12 months when treated with the sodium-glucose cotransporter 2 (SGLT2) inhibitor instead of standard care.

During a panel discussion, Muthiah Vaduganathan, MD (Brigham and Women’s Hospital, Boston, MA), questioned why dapagliflozin, which was shown to improve clinical outcomes in DapaTAVI, would not also improve quality of life.

Bonanad Lozano noted that in prior trials of dapagliflozin, including DECLARE-TIMI 58 and DAPA-HF, patients started with a much higher baseline KCCQ score—around 75—and this only improved by a few points with treatment. With such a large jump in quality of life early after TAVI, “it’s very difficult in 1 year to show a slight improvement” on top of that with dapagliflozin, she said, adding that a difference favoring the drug might have emerged with longer follow-up.

Regardless of the effect on quality of life, the drug reduces mortality so “we have to use it in TAVI patients,” she said.

To TCTMD, Vaduganathan said the lack of a difference in quality of life between trial arms was “somewhat unexpected” considering dapagliflozin’s impact on clinical outcomes, including HF events.

“My general sense is that these were largely minimally symptomatic patients from their underlying conditions like heart failure and most of their symptoms were driven by severe aortic stenosis, and so the large improvement in the standard-of-care arm made it challenging for them to show a differential effect of dapagliflozin,” he said.

DapaTAVI-QoL

Though SGLT2 inhibitors have been shown to reduce HF admissions across a range of high-risk patients, those with severe valvular heart disease or those undergoing valvular interventions like TAVI have been excluded from the prior randomized trials, Bonanad Lozano pointed out.

DapaTAVI, which randomized 1,222 patients with severe aortic stenosis, a history of HF, and at least one high-risk feature (renal insufficiency, diabetes, or impaired LVEF) to dapagliflozin 10 mg once daily or standard care, was the first trial to extend those results to patients undergoing TAVI. Dapagliflozin reduced the primary endpoint of all-cause death or worsening HF by a relative 28% at 1 year.

DapaTAVI-QoL was a prespecified substudy to assess any impact on NYHA class and quality of life according to the KCCQ. It included 862 trial participants (mean age 82.4 years; 49.4% women) who provided 1-year data on these outcomes.

At baseline, mean KCCQ score was 39.9 points in the dapagliflozin arm and 39.1 points in the standard-care arm (P = 0.404). By 3 months, mean scores exceeded 75 points in both groups, with no difference between them; those gains were maintained at 1 year. Results were consistent across subgroups defined by age, sex, LVEF, LV hypertrophy, renal function, diabetes, hypertension, atrial fibrillation, and the use of various medications.

There was, however, a greater decline in NYHA class overall in the dapagliflozin group (P = 0.013). The proportion of patients in NYHA class I at 1 year was 43.5% among patients treated with the SGLT2 inhibitor and 36.2% among those who received standard care.

The beneficial effect of dapagliflozin on death or worsening HF seen in the trial was consistent across the range of baseline KCCQ scores and NYHA class (P = NS for both interactions).

TAVI itself can pretty dramatically improve health status in many people. Muthiah Vaduganathan

For Vaduganathan, the findings don’t change the way he thinks about using SGLT2 inhibitors in patients with severe aortic stenosis. “My sense is this is altering long-term disease progression of the underlying chronic conditions,” he said, “rather than necessarily altering anything about the aortic stenosis itself.”

DapaTAVI shows that “this is a vulnerable population, a high-risk population, and that implementation [of SGLT2 inhibition] around the time of TAVI is safe and effective,” he said. “These data largely also support that TAVI itself can pretty dramatically improve health status in many people.”