Twelve weeks of treatment with empagliflozin in patients with heart failure and reduced ejection fraction: A double-blinded, randomized, and placebo-controlled trial

Am Heart J. 2020 Oct:228:47-56. doi: 10.1016/j.ahj.2020.07.011. Epub 2020 Jul 17.

Abstract

Aims: To investigate the effect of the sodium-glucose co-transporter-2 inhibitor empagliflozin on N-terminal pro-b-type natriuretic peptide (NT-proBNP) in patients with heart failure (HF) and reduced ejection fraction (HFrEF).

Methods and results: Empire HF was an investigator-initiated, multi-center, double-blinded, placebo-controlled, randomized trial. Patients with mildly symptomatic HFrEF, mean (standard deviation (SD)) age 64 (11) years, 85% male, and mean left ventricular ejection fraction 29% (8), on recommended HF therapy were assigned to receive either empagliflozin 10 mg once daily or placebo for 12 weeks. The primary endpoint was the between-group difference in the change of NT-proBNP from baseline to 12 weeks. In total, 95 patients were assigned to empagliflozin and 95 to placebo. No significant difference in the change of NT-proBNP with empagliflozin versus placebo was observed [Empagliflozin: baseline, median (interquartile range (IQR)) 582 (304-1020) pg/mL, 12 weeks, 478 (281-961) pg/mL; Placebo: baseline, 605 (322-1070) pg/mL, 12 weeks, 520 (267-1075) pg/mL, adjusted ratio of change empagliflozin/placebo 0.98; 95% confidence interval (CI) 0.82-1.11, P = 0.7]. Further, no significant difference was observed in accelerometer-measured daily activity level [adjusted mean difference of change, empagliflozin versus placebo, -26.0 accelerometer counts; 95% CI -88.0 to 36.0, P = 0.4] or Kansas City Cardiomyopathy Questionnaire Overall Summary Score [adjusted mean difference of change, empagliflozin versus placebo 0.8; 95% CI -2.3 to 3.9, P = 0.6].

Conclusion: In low-risk patients with HFrEF with mild symptoms and on recommended HF therapy, empagliflozin did not change NT-proBNP after 12 weeks. Further, no change in daily activity level or health status was observed.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Accelerometry / methods*
  • Activities of Daily Living*
  • Benzhydryl Compounds* / administration & dosage
  • Benzhydryl Compounds* / adverse effects
  • Double-Blind Method
  • Female
  • Glucosides* / administration & dosage
  • Glucosides* / adverse effects
  • Heart Failure* / blood
  • Heart Failure* / diagnosis
  • Heart Failure* / drug therapy
  • Heart Failure* / physiopathology
  • Humans
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / blood*
  • Outcome Assessment, Health Care
  • Peptide Fragments / blood*
  • Sodium-Glucose Transporter 2 Inhibitors / administration & dosage
  • Stroke Volume
  • Ventricular Dysfunction, Left / diagnosis*

Substances

  • Benzhydryl Compounds
  • Glucosides
  • Peptide Fragments
  • Sodium-Glucose Transporter 2 Inhibitors
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • empagliflozin