Empagliflozin beneficial and well tolerated in acute heart failure

Empagliflozin provides a significant clinical benefit within 90 days and shows no safety concerns in patients hospitalized for acute heart failure (HF), according to results of the EMPULSE trial reported at the American Heart Association (AHA) Scientific Sessions 2021.

In the trial, patients hospitalized with a primary diagnosis of acute HF (de novo or decompensated chronic HF), regardless of left ventricular ejection fraction (LVEF) or diabetes status, were randomized between ≥24 hours and ≤5 days after admission and stabilization to receive empagliflozin 10 mg (n=265; median age, 71 years; female, 32.5 percent) or placebo (n=265; median age, 70 years; female, 35.1 percent) for 90 days. [Voors AA, et al, AHA 2021]

The primary endpoint of clinical benefit, defined as a composite of death, number of HF events (ie, hospitalizations for HF [HHFs], urgent HF visits, and unplanned outpatient visits), time to first HF event, and change from baseline in Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS) after 90 days of treatment, was 36 percent more likely with empagliflozin vs placebo (53.9 percent vs 39.7 percent; stratified win ratio, 1.36; 95 percent confidence interval [CI], 1.09 to 1.68; p=0.0054).

“Empagliflozin’s effect on the primary endpoint was consistent across subgroups, including in patients with de novo or decompensated chronic HF, those with or without diabetes, and those with baseline LVEF ≤40 percent or >40 percent,” reported lead author Professor Adriaan Voors of the University Medical Centre Groningen in Groningen, the Netherlands.

Empagliflozin-treated patients also had greater improvements in symptoms, as measured by the secondary endpoint of change in KCCQ-TSS score at day 90 (placebo-adjusted mean difference, +4.5 points; 95 percent CI, 0.3 to 8.6; p=0.0347).

In addition, all-cause death or first HF event was reduced by 35 percent with empagliflozin vs placebo (hazard ratio [HR], 0.65; 95 percent CI, 0.43 to 0.99; p=0.0423). Cardiovascular death or first HF event showed a 31 percent reduction (HR, 0.69; 95 percent CI, 0.45 to 1.08; p=0.1021), which did not reach statistical significance.

Patients in the empagliflozin group also had greater reduction in body weight vs those in the placebo group (placebo-adjusted mean difference at day 90, -1.5 kg; 95 percent CI, -2.8 to -0.3; p=0.0137).

“Empagliflozin demonstrated a very benign safety profile, with no safety concerns, in this very vulnerable and sick population of patients hospitalized for acute HF,” said Voors.

Adverse events (AEs) and serious AEs were reported in 70 percent vs 77.3 percent and 32.3 percent vs 43.6 percent of patients in the empagliflozin vs placebo group, respectively. Acute renal failure was reported in 7.7 percent vs 12.1 percent of the patients, while genital infection occurred in 1.2 percent vs 0.4 percent.

“Rates of volume depletion [12.7 percent vs 10.2 percent], hypotension [10.4 percent vs 10.2 percent], and confirmed hypoglycaemia [1.9 percent vs 1.5 percent] were similar between the empagliflozin and placebo groups,” said Voors. “Importantly, no cases of ketoacidosis were reported.”