The following is a summary of “Time to Clinical Benefit of Dapagliflozin in Patients With Heart Failure With Mildly Reduced or Preserved Ejection Fraction” published in the October 2022 issue of Cardiology by Vaduganathan et al.
In the Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure (DELIVER) trial, it was recently shown that dapagliflozin reduces cardiovascular death or worsening heart failure (HF) events in people with HF who have a mildly reduced or preserved ejection fraction. The goal was to see how the benefits of dapagliflozin changed over time for clinically important outcomes in this population. The DELIVER trial was a global phase 3 clinical trial in which HF patients with mildly reduced or preserved ejection fraction were given dapagliflozin or a matching placebo. Inclusion criteria included HF with symptoms, a left ventricular ejection fraction of more than 40%, high levels of natriuretic peptides, and signs of structural heart disease. In this predetermined secondary analysis of the DELIVER trial, hazard ratios (HR) and 95% CIs were estimated for the primary composite endpoint and worsening HF events alone with truncated data at every day after randomization to look at how long it took for dapagliflozin to show clinical benefit.
Then, the time to first and sustained statistical significance of dapagliflozin for these endpoints were examined. Participants were enrolled from August 2018 to December 2020, and the data for this secondary analysis were analyzed from April to September 2022. The main result was the time until the first death from heart disease or worsening of HF (hospitalization for HF or an urgent HF visit requiring intravenous HF therapies). In total, 6,263 patients from 350 centers in 20 countries were randomly assigned. The average mean (standard deviation) age of the 6,263 patients included was 71.7 (9.6) years, and 43.9% were women. During a median (IQR) follow-up period of 2.3 (1.7-2.8) years, 1,122 primary end point events happened, with an incidence rate per 100 patient-years of 8.7 (95% CI, 8.2-9.2). The time to first nominal statistical significance for the primary endpoint was 13 days (HR, 0.45; 95% CI, 0.20-0.99; P=.046), and significance lasted from day 15 onwards.
The first and last statistical significance was found for worsening HF events (HR, 0.45; 95% CI, 0.21-0.96; P=.04) 16 days after randomization. Significant benefits were still seen for the primary endpoint and worsening HF events at 30 days, 90 days, 6 months, 1 year, 2 years, and the final follow-up (HR, 0.82; 95% CI, 0.73–0.92 for the primary endpoint; HR, 0.79; 95% CI, 0.69–0.91 for worsening HF events). In the DELIVER trial, dapagliflozin led to early and long-lasting reductions in clinical events in patients with HF who had a mildly reduced or preserved ejection fraction. These reductions were statistically significant within 2 weeks of starting treatment.
Source: jamanetwork.com/journals/jamacardiology/fullarticle/2796867
