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

Sacubitril/valsartan over 12?weeks compared with enalapril did not significantly improve peak oxygen consumption (VO2) in patients with heart failure with reduced ejection fraction (HFrEF). CI, confidence interval; LSM, least squares mean; LVEF, left ventricular ejection fraction; NYHA, New York Heart Association; SE, standard error.

AbstractAims

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.