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

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 (LVEF ≤40%, NYHA 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 (peak 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 VE/VCO2 slope, exercise capacity at first ventilatory threshold (VT1) or Borg scale at either Week 6 or Week 12. Change in heart rate at VT1 was lower in the sacubitril/valsartan group compared with the enalapril group at Week 12 (mean -3.75 beats/min; 95% CI: -7.03, -0.48; p=0.0248). The safety of sacubitril/valsartan was comparable to enalapril. CONCLUSION Short-term treatment with sacubitril/valsartan for 12 weeks did not result in significant benefits on peak VO2 when compared with enalapril. This article is protected by copyright. All rights reserved.