A randomized clinical trial on the short-term effects of 12-week sacubitril/valsartan vs. enalapril on peak oxygen consumption in patients with heart failure with reduced ejection fraction: results from the ACTIVITY-HF study

Eur J Heart Fail. 2021 Dec;23(12):2073-2082. doi: 10.1002/ejhf.2355. Epub 2021 Oct 12.

Abstract

Aims: ACTIVITY-HF was a randomized, double-blind, active-controlled study, which assessed the short-term effect of sacubitril/valsartan compared with the active comparator enalapril on improving maximal exercise capacity in patients with heart failure with reduced ejection fraction (HFrEF).

Methods and results: A total of 201 ambulatory patients with HFrEF (left ventricular ejection fraction ≤ 40%, New York Heart Association class III) across 34 centres in Germany were randomized (1:1) to receive sacubitril/valsartan 97/103 mg bid (n = 103) or enalapril 10 mg bid (n = 98). The primary endpoint of the study was the change from baseline in peak oxygen consumption (VO2 ; adjusted to body weight) after 12 weeks, and the key secondary endpoint was change from baseline in peak VO2 after 6 weeks. The study population was predominantly male (81.1%) with a mean age of 66.9 years and a body mass index of 29.4 kg/m2 . Change in peak VO2 from baseline to Week 12 was similar between sacubitril/valsartan and enalapril groups [least squares mean difference: 0.32 mL/min/kg; 95% confidence interval (CI) -0.21, 0.85; P = 0.2327]. Similarly, no significant differences were observed between the two treatment groups in minute ventilation to carbon dioxide production slope, exercise capacity at first ventilatory threshold or Borg scale at either Week 6 or Week 12. Change in heart rate at first ventilatory threshold was lower in the sacubitril/valsartan group compared with the enalapril group at Week 12 (mean -3.75 bpm; 95% CI -7.03, -0.48; P = 0.0248). The safety of sacubitril/valsartan was comparable to enalapril.

Conclusion: In patients with HFrEF, short-term treatment with sacubitril/valsartan for 12 weeks did not result in significant benefits on peak VO2 when compared with enalapril.

Keywords: Exercise capacity; Physical activity; Quality of life; Sacubitril/valsartan; Six-minute walk test.

Publication types

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

MeSH terms

  • Aged
  • Aminobutyrates* / therapeutic use
  • Angiotensin Receptor Antagonists / therapeutic use
  • Biphenyl Compounds* / therapeutic use
  • Drug Combinations
  • Enalapril* / therapeutic use
  • Female
  • Heart Failure*
  • Humans
  • Male
  • Oxygen Consumption
  • Stroke Volume
  • Tetrazoles / therapeutic use
  • Valsartan* / therapeutic use
  • Ventricular Function, Left

Substances

  • Aminobutyrates
  • Angiotensin Receptor Antagonists
  • Biphenyl Compounds
  • Drug Combinations
  • Tetrazoles
  • sacubitril
  • Enalapril
  • Valsartan