Empagliflozin in Patients Hospitalized for Acute Heart Failure - EMPULSE

Oct 31, 2022
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Author/Summarized by Author:
Anthony A. Bavry, MD,MPH,FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Boehringer Ingelheim; Eli Lilly
Date Presented:
04/04/2022
Date Published:
10/18/2022
Date Updated:
10/31/2022
Original Posted Date:
11/14/2021
References

Contribution To Literature:

Highlighted text has been updated as of October 31, 2022.

The EMPULSE trial showed that empagliflozin was beneficial at reducing adverse events among acute decompensated heart failure patients.

Description:

The goal of the trial was to evaluate empagliflozin compared with placebo among patients with acute decompensated heart failure. Empagliflozin is a sodium-glucose cotransporter-2 (SGLT2) inhibitor, which has been shown to reduce the risk of cardiovascular death or heart failure hospitalization among patients with chronic heart failure.

Study Design

  • Randomization
  • Parallel

Participants with acute heart failure were randomized to empagliflozin 10 mg daily (n = 265) versus placebo (n = 265).

  • Total number of enrollees: 530
  • Duration of follow-up: 90 days
  • Mean patient age: 71 years
  • Percentage female: 33%
  • Percentage with diabetes: 47%

Inclusion criteria:

  • Patients admitted to the hospital with acute heart failure regardless of ejection fraction or diabetes status
  • Systolic blood pressure ≥100 mm Hg and no symptoms of hypotension within 6 hours
  • No increase in intravenous (IV) diuretic dose within 6 hours
  • No IV vasodilators, including nitrates, within 6 hours
  • No IV inotropic drugs within 24 hours
  • N-terminal pro–B-type natriuretic peptide (NT-proBNP) ≥1600 pg/ml or BNP ≥400 pg/ml during hospitalization or within 72 hours prior to admission

Other salient features/characteristics:

  • Median left ventricular ejection fraction: 31%

Principal Findings:

The primary analysis was assessed by a stratified win ratio, defined as a composite of death, number of heart failure events, time to first heart failure event, and change in Kansas City Cardiomyopathy Questionnaire-Total Symptom Score (KCCQ-TSS) from baseline to 90 days. Clinical benefit occurred at a rate of 53.9% in the empagliflozin group compared with 39.7% in the placebo group (p = 0.0054). There was no evidence for treatment interaction among various tested subgroups.

Secondary outcomes:

  • Death: 4.2% in the empagliflozin group vs. 8.3% in the placebo group
  • Heart failure event: 10.6% in the empagliflozin group vs. 14.7% in the placebo group
  • Change in KCCQ-TSS: 4.5 points for the empagliflozin group vs. the placebo group (p = 0.035)
  • Acute renal failure: 7.7% in the empagliflozin group vs. 12.1% in the placebo group
  • Body weight change: -1.5 kg for the empagliflozin group vs. the placebo group (p = 0.014)

Effects of empagliflozin on quality of life:

Patients were divided into tertiles based on Kansas City Cardiomyopathy Questionnaire-total symptom score (KCCQ-TSS) (comparisons for empagliflozin vs. placebo; p for interaction = 0.94).

  • Low tertile: Win ratio, 1.49
  • Middle tertile: Win ratio, 1.37
  • High tertile: Win ratio, 1.48

Effects of empagliflozin on weight loss:

  • Body weight change (kg) from baseline to day 15: -3.20 kg in the empagliflozin group vs. -1.23 in the placebo group (p < 0.0001)
  • Body weight change (kg) from baseline to day 30: -3.19 kg in the empagliflozin group vs. -1.45 in the placebo group (p = 0.0007)
  • Body weight change (kg) from baseline to day 90: -2.36 kg in the empagliflozin group vs. -0.83 in the placebo group (p = 0.014)

Interpretation:

Among patients with acute decompensated heart failure, empagliflozin versus placebo was associated with significant clinical benefit at 90 days. This trial enrolled participants regardless of ejection fraction or diabetes status and there was no evidence for treatment interaction based on either of these variables. The benefit of empagliflozin was independent of symptomatic impairment at baseline. Empagliflozin versus placebo was also associated with fewer deaths, improvement in quality of life, and greater reduction in body weight. There were no safety concerns with empagliflozin. Empagliflozin was also associated with improved weight loss (decongestion) compared with placebo.

References:

Biegus J, Voors AA, Collins SP, et al. Impact of Empagliflozin on Decongestion in Acute Heart Failure: The EMPULSE Trial. Eur Heart J 2022;Oct 18:[Epub ahead of print].

Kosiborod MN, Angermann CE, Collins SP, et al. Effects of Empagliflozin on Symptoms, Physical Limitations and Quality of Life in Patients Hospitalized for Acute Heart Failure: Results From the EMPULSE Trial. Circulation 2022;146:279-88.

Editorial: Anker SD, Usman MS, Butler J. SGLT2 Inhibitors: From Antihyperglycemic Agents to All-Around Heart Failure Therapy. Circulation 2022;146:299-302.

Presented by Dr. Mikhail Kosiborod at the American College of Cardiology Annual Scientific Session (ACC 2022), Washington, DC, April 4, 2022.

Presented by Dr. Adriaan A. Voors at the American Heart Association Virtual Annual Scientific Sessions (AHA 2021), November 14, 2021.

Clinical Topics: Geriatric Cardiology, Heart Failure and Cardiomyopathies, Acute Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: ACC Annual Scientific Session, ACC22, AHA21, AHA Annual Scientific Sessions, Blood Pressure, Body Weight, Geriatrics, Heart Failure, Natriuretic Peptide, Brain, Quality of Life, Sodium-Glucose Transporter 2 Inhibitors, Stroke Volume, Weight Loss


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