DapaTAVI Trial Shows Farxiga Significantly Lowers Risk of Death After Transcatheter Aortic-Valve Implantation in Older Patients

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Results from the Phase IV DapaTAVI trial (NCT04696185) show that the addition of Farxiga (dapagliflozin) to standard care in older patients with severe aortic stenosis undergoing transcatheter aortic-valve implantation (TAVI) lowered the risk of death or worsening heart failure by 28%. These findings, published by The New England Journal of Medicine, demonstrated consistent benefits with administration of Farxiga across patient subgroups with a favorable safety profile.^1,2

“Many patients with aortic stenosis who are treated with TAVI still face a high risk of hospitalization for heart failure, which is associated with high mortality among these patients,” the study authors wrote. “Sodium–glucose cotransporter 2 (SGLT2) inhibitors have been shown to be effective in reducing heart-failure–related admissions across a wide spectrum of high-risk patients. Both US and European clinical practice guidelines recommend the use of SGLT2 inhibitors in patients with heart failure regardless of their left ventricular ejection fraction or diabetes status. However, the supporting evidence for this recommendation is less robust when it comes to patients with heart failure attributable to reversible conditions, such as aortic stenosis.”¹

Farxiga is an SGLT2 inhibitor that was initially approved by the FDA in 2014 to lower HbA1c in patients with type 2 diabetes mellitus. Farxiga has been found to reduce sodium reabsorption and increase the delivery of sodium to the distal tubule. Although the mechanism of the benefit with Farxiga in treating heart failure has yet to be determined, investigators have linked its use to a decrease in sodium and volume overload, which leads to improved cardiac function.³

Trial Design

Investigators conducted the DapaTAVI study using a pragmatic, controlled, prospective, randomized, open-label, evaluator-blind clinical trial design to compare the benefits of oral Farxiga at a dose of 10 mg once daily vs. standard care in patients with severe aortic stenosis discharged after TAVI was performed. The investigator-initiated clinical trial was performed at 39 sites throughout Spain.

All patients enrolled in the trial had a history of heart failure with at least one of either renal insufficiency, diabetes, or left ventricular systolic dysfunction. Patients enrolled in the trial had a mean age of 82 years, with 72% above 80 years of age and more than 7% above 90 years of age.

Investigators randomly assigned 620 patients to receive Farxiga and 637 patients to receive standard care alone after TAVI. Following patient exclusions, 1222 combined participants were included in the trial’s primary analysis. The primary endpoint of DapaTAVI was a composite of death from any cause or worsening of heart failure, which was defined as hospitalization or urgent visit at one year of follow-up.

Results show occurrence of a primary endpoint event in 15.0% of patients in the Farxiga cohort compared to 20.1% of patients in the standard care cohort (hazard ratio, 0.72; 95% confidence interval [CI], 0.55 to 0.95; P=0.02). Death from any cause was reported in 7.8% of patients in the Farxiga cohort compared to 8.9% of patients in the standard care cohort (hazard ratio, 0.87; 95% CI, 0.59 to 1.28).

Worsening of heart failure was observed in 9.4% of patients in the Farxiga cohort compared to 14.4% of patients in the standard care cohort (subhazard ratio, 0.63; 95% CI, 0.45 to 0.88). Incidence of a primary endpoint event was found to be consistent across all prespecified patients subgroups and was not affected by renal insufficiency, diabetes, or left ventricular systolic dysfunction.

“Our results appear to confirm that SGLT2 inhibitors are safe in older patients and are associated with clinical benefits, which is important given the low frequency of prescriptions for SGLT2 inhibitors among older patients,” the study authors wrote. “Another relevant aspect of our current trial is that almost half the patients were women. In previous trials of SGLT2 inhibitors, women have been underrepresented.”¹

References

1. Raposeiras-Roubin S., et al. Dapagliflozin in Patients Undergoing Transcatheter Aortic-Valve Implantation. N Engl J Med 2025;392:1396-1405. DOI: 10.1056/NEJMoa2500366. VOL. 392 NO. 14.

2. Dapagliflozin After Transcatheter Aortic Valve Implantation (DapaTAVI). ClinicalTrials.gov. Updated January 10, 2025. Accessed April 16, 2025. https://clinicaltrials.gov/study/NCT04696185

3. Farxiga full prescribing information. May 2020, Accessed April 16, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/202293s020lbl.pdf