SGLT2 inhibitors foundational therapy in all HF patients regardless of EF: Pooled analysis of DAPA-HF and DELIVER

Previous studies have shown that the SGLT2 inhibitor dapagliflozin reduces cardiovascular mortality and morbidity in patients with diabetes, chronic kidney disease, and heart failure with reduced ejection fraction.

According to Pooled analysis of DAPA-HF and DELIVER trials SGLT2 inhibitor dapagliflozin may be foundational therapy in all patients of heart patients regardless of ejection fraction.

This pre-specified patient-level meta-analysis combined the DAPA-HF2 and DELIVER3 trials of the SGLT2 inhibitor dapagliflozin in patients with heart failure. DAPA-HF enrolled patients with reduced ejection fraction (40% or less) and DELIVER enrolled patients with mildly reduced and preserved ejection fraction (above 40%). Both trials randomly allocated participants to dapagliflozin 10 mg once daily or placebo.

The first aim of this analysis was to examine the effect of dapagliflozin on a number of secondary outcomes that each trial alone was not powered to examine. The second aim was to examine if dapagliflozin was effective across the entire range of ejection fraction, since the EMPEROR-Preserved trial previously suggested that the effect of empagliflozin, another SGLT2 inhibitor, may be attenuated in patients with higher ejection fraction.4

A total of 11,007 patients were randomised to dapagliflozin or placebo in the two trials. Survival analysis was used to examine the effect of dapagliflozin on death from cardiovascular causes; death from any cause; total hospital admissions for heart failure; and the composite of death from cardiovascular causes, myocardial infarction, or stroke (major adverse cardiovascular events; MACE).

The average age of participants was 69 years and 35% were women. The median follow up was 1.8 years. Dapagliflozin reduced the risk of death from cardiovascular causes by 14% (hazard ratio [HR] 0.86; 95% confidence interval [CI] 0.76–0.97; p=0.01), death from any cause by 10% (HR 0.90; 95% CI 0.82–0.99; p=0.03), total hospital admissions for heart failure by 29% (relative risk [RR] 0.71; 95% CI 0.65–0.78; p<0.001) and MACE by 11% (HR 0.90; 95% CI 0.81–1.00; p=0.045). There was no evidence that the effect of dapagliflozin differed by ejection fraction for any of the outcomes.

Study author Professor Pardeep Jhund of the University of Glasgow, UK said: "Our findings confirm that all patients with heart failure, regardless of ejection fraction, may benefit from dapagliflozin in addition to any other heart failure therapy they are receiving."

References:

1. McMurray JJV, Solomon SD, Inzucchi SE, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019;381:1995-2008.

2. DELIVER is being presented during Hot Line Session 4 at ESC Congress 2022 by Professor Scott Solomon.

3. Butler J, Packer M, Filippatos G, et al. Effect of empagliflozin in patients with heart failure across the spectrum of left ventricular ejection fraction. Eur Heart J. 2022;43:416–426.