AHA: Empagliflozin effective and well tolerated in acute heart failure

18 Nov 2021
Empagliflozin effective and well tolerated in acute heart failure

Empagliflozin provides a significant clinical benefit within 90 days and is well tolerated 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 in ≥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]

Results showed that patients treated with empagliflozin were 36 percent more likely to experience a clinical benefit (primary endpoint), 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, compared with those treated with placebo (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).

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).

Reduction in body weight was also greater in the empagliflozin vs 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 patient population,” 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.”

 

Empagliflozin in HF patients with LVEF ≥50 percent

Also reported at AHA 2021 were results of the EMPEROR-Preserved trial in a subgroup of patients with HF with baseline LVEF ≥50 percent (ie, true HF with preserved ejection fraction [HFpEF], according to the European Society of Cardiology’s 2021 HF guidelines). [Anker SD, et al, AHA 2021; Eur Heart J 2021;doi:10.1093/eurheartj/ehab368]

The trial included 5,988 HF patients with baseline LVEF >40 percent. Among 4,005 patients with baseline LVEF ≥50 percent (mean age, 72.8 years; female, 50 percent), empagliflozin reduced the risk of the primary composite outcome of cardiovascular death or HHF by 17 percent (HR, 0.83; 95 percent CI, 0.71 to 0.98; p=0.024) and the risk of first HHF by 22 percent (HR, 0.78; 95 percent CI, 0.64 to 0.95; p=0.013) vs placebo.

“These results in patients with HFpEF showed no interaction with those with baseline LVEF of 41–49 percent [ie, HF with mildly reduced ejection fraction (HFmrEF)],” reported study author Professor Stefan Anker of the Charité University Hospital Berlin, Germany.

 

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