Massimo F Piepoli1, Rizwan I Hussain2, Josep Comin-Colet3, Ramon Dosantos4, Philippe Ferber2, Tiny Jaarsma5,6, Frank Edelmann7,8,9. 1. Heart Failure Unit, Cardiology Department, G. da Saliceto Polichirurgico Hospital, Piacenza, Italy, and Scuola Superiore S. Anna, Piacenza, Italy. 2. Novartis Pharma AG, Basel, Switzerland. 3. Community Heart Failure Program, Department of Cardiology, Bellvitge University Hospital and Biomedical Research Institute (IDIBELL), University of Barcelona, Hospitalet de Llobregat, Barcelona, Spain. 4. Biometrics Department, TFS SL, Barcelona, Spain. 5. Division of Nursing Science, Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden. 6. Julius Center, University Medical Center Utrecht, Utrecht, The Netherlands. 7. Department of Internal Medicine and Cardiology, Campus Virchow Klinikum, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany. 8. Berlin Institute of Health, Berlin, Germany. 9. German Centre for Cardiovascular Research (DZHK), partner site Berlin, Berlin, Germany.
Abstract
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.
RCT Entities:
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.
Authors: Lorenzo Stretti; Dauphine Zippo; Andrew J S Coats; Markus S Anker; Stephan von Haehling; Marco Metra; Daniela Tomasoni Journal: ESC Heart Fail Date: 2021-12-16