According to results from a pivotal trial published in The New England Journal of Medicine, the use of the sodium–glucose cotransporter 2 (SGLT2) inhibitor empagliflozin was linked with a lower combined risk for cardiovascular (CV) death or hospitalization for heart failure (HF) compared with placebo in patients receiving recommended therapy for heart failure, regardless of the presence of diabetes.

These findings were also presented at the 2020 European Society of Cardiology Virtual Congress. In the double-blind Empagliflozin Outcome Trial in Patients with Chronic Heart Failure and a Reduced Ejection Fraction (EMPEROR-Reduced), 3,730 adult patients with class II, III, or IV HF and an ejection fraction of ≤40% were randomly assigned to receive 10 mg empagliflozin or placebo once daily, in addition to recommended therapy. 

The primary outcome of the study was a composite of CV-related death or hospitalization for exacerbation of HF. The study included a total of 1,863 patients who received empagliflozin (average age, 67.2 years ± 10.8 years; 23.5% females; 71.1% Caucasian), and 1,867 participants received placebo (average age, 66.5 years ± 11.2 years; 24.4% females; 69.8% Caucasian). The results revealed that during a median of 16 months, a primary outcome event occurred in 361 patients (19.4%) in the empagliflozin group and in 462 patients (24.7%) in the placebo group (hazard ratio [HR], 0.75; 95% CI, 0.65-0.86; P <.001). 

The effect of empagliflozin was detected in patients with and without diabetes. Results also revealed that the total number of hospitalizations for HF was smaller in the empagliflozin versus the placebo group (HR, 0.70; 95% CI, 0.58-0.85; P <.001). In addition, the annual rate of decline in estimated glomerular filtration rate was slower in the empagliflozin versus the placebo group (–0.55 vs. –2.28 mL/min/1.73 m2 of body surface area per year, respectively; P <.001), and patients treated with empagliflozin versus placebo had a lower risk for serious renal outcomes. Patients who received empagliflozin reported more incidences of uncomplicated genital tract infection. They concluded that among patients receiving recommended therapy for HF, those in the empagliflozin group had a smaller risk of CV death or hospitalization for HF than those in the placebo group, regardless of the existence of diabetes.

The researchers, led by Dr. Milton Parker, noted, “In our trial, the combined risk for cardiovascular death or hospitalization for HF was 25% lower among the patients who received empagliflozin than among those who received placebo, a difference that was primarily related to a 31% lower risk for hospitalization for heart failure. These benefits were seen in patients receiving any of the currently recommended drugs for heart failure, including sacubitril–valsartan, and were seen regardless of the presence or absence of diabetes. In addition, empagliflozin was associated with a lower number of hospitalizations for heart failure and with a slower rate of decline in the estimated glomerular filtration rate; the latter effect was accompanied by a lower risk of serious renal outcomes.” 

In an accompanying editorial, Dr. John A. Jarcho stated that the study’s findings, along with the results from the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial, “substantially strengthen” the justification for using SGLT2 inhibitors in patients with HF and reduced ejection fraction. 
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