Empagliflozin significantly reduces CV and renal risk

Data from the EMPEROR-Reduced trial (NCT03057977) showed that empagliflozin reduces the risk of cardiovascular (CV) death or hospitalisation for heart failure (HF) in patients with HF and a reduced ejection fraction (HFrEF).

 This trial was designed to evaluate the effects of 10 mg empagliflozin once daily compared with placebo in patients with HFreEF, with or without diabetes, who were receiving treatment for HF [1,2]. The primary endpoint was the composite of CV death or hospitalisation for HF. The first secondary endpoint was total (first and recurrent) HF hospitalisation and the second secondary endpoint was the slope of decline in glomerular filtration rate (GFR) over time. A total of 3,730 patients with HF and a left ventricular ejection fraction of 40% or less, with or without diabetes, were randomised to 10 mg empagliflozin once daily or placebo. Median follow-up was 16 months. “It is noteworthy, that these patients were sicker and were more high risk than patients included in other studies such as DAPA-HF”, Dr Milton Packer (Baylor University Medical Center, Dallas, USA) said [3].

The primary endpoint occurred in 361 patients in the empagliflozin group (15.8/100 patient-years) and 462 patients in the placebo group (21.0/100 patient-years; HR 0.75; 95% CI 0.65-0.86; P<0.0001). Empagliflozin reduced the total number of hospitalisations for heart failure (HR 0.70; 95% CI 0.58-0.85; P<0.001). Regarding the second secondary endpoint, there was a difference in slope of 1.7 mL/min/1.73m²/year favouring the empagliflozin arm (95% CI 1.1-2.4; P<0.0001). In 966 patients, eGFR was reassessed at the end of the trial, 23-45 days after withdrawal of double-blind therapy, and over 16 months. The eGFR decreased by -4.2 mL/min/1.73m² in the placebo group, and -0.9 mL/min/1.73m² in the empagliflozin group (P<0.001). Adverse renal events occurred in 30 patients in the empagliflozin group and in 58 patients in the placebo group (HR 0.50; 95% CI 0.32-0.77; P<0.01), which translates into a 50% risk reduction.

1. Packer M, et al. N Engl J Med 2020; 383:1413-1424.
2. Packer M, et al. Eur J Heart Fail. 2019;21:1270–1278.
3. Packer M. Primary results. EASD 2020. Session: Empagliflozin for the treatment of chronic heart failure and a reduced ejection fraction in patients with and without diabetes: new results of the EMPEROR-Reduced trial.