Sacubitril/valsartan did not significantly improve 6-minute walk test distance (difference 8.98 m; 97.5% CI -1.31 to 19.27; P=0.0503) or daytime physical activity compared with enalapril at 12 weeks.
RCT (n=621)
1:1
Does sacubitril/valsartan improve 6-min walk test distance and daily physical activity compared to enalapril in patients with stable symptomatic HFrEF?
Sacubitril/valsartan did not significantly improve 6-minute walk test distance or daily physical activity compared to enalapril over 12 weeks in patients with stable HFrEF.
Effect estimate: treatment difference 8.98 m (95% CI -1.31, 19.27)
Absolute Event Rate: 35.09% vs 26.11%
p-value: p=0.0503
Aims OUTSTEP‐HF compared the effect of sacubitril/valsartan vs. enalapril on 6‐min walk test (6MWT) distance, non‐sedentary daytime physical activity and heart failure (HF) symptoms in patients with HF with reduced ejection fraction (HFrEF). Methods and results Ambulatory patients ( n = 621) with stable symptomatic HFrEF were randomised 1:1 to sacubitril/valsartan ( n = 310) or enalapril ( n = 311). Changes in physical activity and mean daily non‐sedentary daytime activity from baseline to Week 12 were measured using 6MWT and a wrist‐worn accelerometer device, respectively. After 12 weeks, 6MWT improved by 35.09 m with sacubitril/valsartan 97.5% confidence interval (CI) 27.85, 42.32 and by 26.11 m with enalapril (97.5% CI 18.78, 33.43); however, there was no significant difference between groups least squares means treatment difference: 8.98 m (97.5% CI −1.31, 19.27); P = 0.0503. Mean daily non‐sedentary daytime activity decreased by 27 min with sacubitril/valsartan and by 21 min with enalapril least squares means treatment difference: −6 min (97.5% CI −25.7, 13.4), P = 0.4769 after 12 weeks. 6MWT improved by ≥30 m in 51% of patients in the sacubitril/valsartan group vs. 44% of patients treated with enalapril (odds ratio 1.251, 95% CI 0.895, 1.748). At Week 4, non‐sedentary daytime activity increased by ≥10% in 58% of patients treated with sacubitril/valsartan vs. 64% with enalapril; 58% of patients treated with sacubitril/valsartan reported improved HF symptoms as assessed by patient global assessment vs. 43% with enalapril. However, these differences did not persist at Week 12. Conclusion After 12 weeks of treatment, there was no significant benefit of sacubitril/valsartan on either 6MWT or daytime physical activity measured by actigraphy compared with enalapril.
Piepoli et al. (Mon,) conducted a rct in chronic heart failure with reduced ejection fraction (HFrEF) (n=621). sacubitril/valsartan vs. enalapril was evaluated on change in 6-min walk test (6MWT) distance from baseline to Week 12 (treatment difference 8.98 m, 95% CI -1.31, 19.27, p=0.0503). Sacubitril/valsartan did not significantly improve 6-minute walk test distance (difference 8.98 m; 97.5% CI -1.31 to 19.27; P=0.0503) or daytime physical activity compared with enalapril at 12 weeks.