Dapagliflozin Associated With Long-Term Event-Free Survival in Adults With HF

Long-term use of dapagliflozin in older patients with heart failure and mildly reduced or preserved ejection fraction may extend event-free survival.

Long-term use of dapagliflozin may extend event-free survival for up to 2.5 years in middle-aged and older patients with heart failure (HF) and mildly reduced or preserved ejection fraction (EF), according to a study in the Journal of the American College of Cardiology.

Researchers reported results from a prespecified analysis of the DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure) trial.

The phase 3, randomized, double-blind, placebo-controlled trial enrolled adults aged 40 years or older with symptomatic HF (New York Heart Association functional class II-IV), left ventricular (LV) EF higher than 40%, increased levels of N-terminal pro-B-type natriuretic peptide, and evidence of structural heart disease.

The primary endpoint was the time to first occurrence of the composite of death from cardiovascular causes or worsening HF event.

A total of 6263 patients with HF with mildly reduced or preserved ejection fraction were randomly assigned across 350 sites in 20 countries from September 1, 2018, to January 18, 2021. Participants’ mean age at randomization was 72±10 years.

These data reinforce the primary results of the relative benefits of dapagliflozin during the DELIVER trial, and provide alternative reframing of the absolute benefits with use of dapagliflozin during the remaining lifetime of the individual.

After a median follow-up of 2.3 years, 1122 primary endpoint events occurred with an incidence rate of 8.7 per 100 patient-years (95% CI, 8.2-9.2 per 100 patient-years).

The estimated event-free survival at age 55 years from the primary endpoint was 11.8 years (95% CI, 9.8-13.9 years) in participants who used dapagliflozin vs 9.8 years (95% CI, 8.2-11.5 years) in those who received placebo (difference, 2.0 years [95% CI, -0.6 to 4.6 years]; P =.14). The estimated event-free survival at age 65 years was 12.1 years (95% CI, 11.0-13.2 years) for dapagliflozin and 9.7 years (95% CI, 8.8-10.7 years) for placebo (difference, 2.3 years [95% CI, 0.9-3.8 years]; P =.002).

When participants reached age 75 years, the estimated event-free survival was 10.6 years (95% CI, 9.7-11.5 years) with dapagliflozin and 9.4 years (95% CI, 8.6-10.3 years) with placebo (difference, 1.2 years [95% CI, -0.1 to 2.4 years]; P =.063).

Absolute benefits in mean event-free survival gains with dapagliflozin vs placebo for about 1.0 to 2.5 years were observed for all ages with attenuation after approximately age 80 years. Beginning at age 65 years, the mean event-free survival was greater with dapagliflozin vs placebo in 14 subgroups, including those based on LVEF, type 2 diabetes status, and concomitant use of other HF therapies.

The mean event-free survival gains were comparable in patients with HF with improved ejection fraction (2.7 years [95% CI, -0.4 to 5.9 years]) and those with an LVEF always higher than 40% (2.3 years [95% CI, 0.7-3.9 years]).

Among several limitations, the researchers did not have linked records across the 20 countries to allow long-term follow-up to validate the actuarial estimates. In addition, adherence to dapagliflozin in real-world settings may be different than what was observed in the DELIVER participants, and the analysis does not account for interval events that occur over time.

“These data reinforce the primary results of the relative benefits of dapagliflozin during the DELIVER trial, and provide alternative reframing of the absolute benefits with use of dapagliflozin during the remaining lifetime of the individual,” wrote the investigators.

Disclosure: The DELIVER trial was funded by AstraZeneca. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

References:

Vaduganathan M, Claggett BL, Jhund P, et al. Estimated long-term benefit of dapagliflozin in patients with heart failure. J Am Coll Cardiol. Published online August 27, 2022;80(19):1775-1784. doi: 10.1016/j.jacc.2022.08.745