Douglas L Mann1, Michael M Givertz2, Justin M Vader1, Randall C Starling3, Palak Shah4, Steven E McNulty5, Kevin J Anstrom5, Kenneth B Margulies6, Michael S Kiernan7, Claudius Mahr8, Divya Gupta9, Margaret M Redfield10, Anuradha Lala11, Gregory D Lewis12, Adam D DeVore5,13, Patrice Desvigne-Nickens14, Adrian F Hernandez5,13, Eugene Braunwald2. 1. Department of Medicine, Washington University in St Louis, St Louis, Missouri. 2. Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. 3. Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio. 4. Inova Heart and Vascular Institute, Falls Church, Virginia. 5. Duke Clinical Research Institute, Duke University, Durham, North Carolina. 6. Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia. 7. Department of Medicine, Tufts Medical Center, Boston, Massachusetts. 8. Department of Medicine, University of Washington, Seattle. 9. Department of Medicine, Emory University, Atlanta, Georgia. 10. Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota. 11. Icahn School of Medicine at Mount Sinai, New York, New York. 12. Department of Medicine, Massachusetts General Hospital, Boston. 13. Department of Medicine, Duke University, Durham, North Carolina. 14. Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, Baltimore, Maryland.
Abstract
Importance: The use of sacubitril/valsartan is not endorsed by practice guidelines for use in patients with New York Heart Association class IV heart failure with a reduced ejection fraction because of limited clinical experience in this population. Objective: To compare treatment with sacubitril/valsartan treatment with valsartan in patients with advanced heart failure and a reduced ejection fraction and recent New York Heart Association class IV symptoms. Design, Setting, and Participants: A double-blind randomized clinical trial was conducted; a total of 335 patients with advanced heart failure were included. The trial began on March 2, 2017, and was stopped early on March 23, 2020, owing to COVID-19 risk. Intervention: Patients were randomized to receive sacubitril/valsartan (target dose, 200 mg twice daily) or valsartan (target dose, 160 mg twice daily) in addition to recommended therapy. Main Outcomes and Measures: The area under the curve (AUC) for the ratio of N-terminal pro-brain natriuretic peptide (NT-proBNP) compared with baseline measured through 24 weeks of therapy. Results: Of the 335 patients included in the analysis, 245 were men (73%); mean (SD) age was 59.4 (13.5) years. Seventy-two eligible patients (18%) were not able to tolerate sacubitril/valsartan, 100 mg/d, during the short run-in period, and 49 patients (29%) discontinued sacubitril/valsartan during the 24 weeks of the trial. The median NT-proBNP AUC for the valsartan treatment arm (n = 168) was 1.19 (IQR, 0.91-1.64), whereas the AUC for the sacubitril/valsartan treatment arm (n = 167) was 1.08 (IQR, 0.75-1.60). The estimated ratio of change in the NT-proBNP AUC was 0.95 (95% CI 0.84-1.08; P = .45). Compared with valsartan, treatment with sacubitril/valsartan did not improve the clinical composite of number of days alive, out of hospital, and free from heart failure events. Aside from a statistically significant increase in non-life-threatening hyperkalemia in the sacubitril/valsartan arm (28 [17%] vs 15 [9%]; P = .04), there were no observed safety concerns. Conclusions and Relevance: The findings of this trial showed that, in patients with chronic advanced heart failure with a reduced ejection fraction, there was no statistically significant difference between sacubitril/valsartan and valsartan with respect to reducing NT-proBNP levels. Trial Registration: ClinicalTrials.gov Identifier: NCT02816736.
Importance: The use of sacubitril/valsartan is not endorsed by practice guidelines for use in patients with New York Heart Association class IV heart failure with a reduced ejection fraction because of limited clinical experience in this population. Objective: To compare treatment with sacubitril/valsartan treatment with valsartan in patients with advanced heart failure and a reduced ejection fraction and recent New York Heart Association class IV symptoms. Design, Setting, and Participants: A double-blind randomized clinical trial was conducted; a total of 335 patients with advanced heart failure were included. The trial began on March 2, 2017, and was stopped early on March 23, 2020, owing to COVID-19 risk. Intervention: Patients were randomized to receive sacubitril/valsartan (target dose, 200 mg twice daily) or valsartan (target dose, 160 mg twice daily) in addition to recommended therapy. Main Outcomes and Measures: The area under the curve (AUC) for the ratio of N-terminal pro-brain natriuretic peptide (NT-proBNP) compared with baseline measured through 24 weeks of therapy. Results: Of the 335 patients included in the analysis, 245 were men (73%); mean (SD) age was 59.4 (13.5) years. Seventy-two eligible patients (18%) were not able to tolerate sacubitril/valsartan, 100 mg/d, during the short run-in period, and 49 patients (29%) discontinued sacubitril/valsartan during the 24 weeks of the trial. The median NT-proBNP AUC for the valsartan treatment arm (n = 168) was 1.19 (IQR, 0.91-1.64), whereas the AUC for the sacubitril/valsartan treatment arm (n = 167) was 1.08 (IQR, 0.75-1.60). The estimated ratio of change in the NT-proBNP AUC was 0.95 (95% CI 0.84-1.08; P = .45). Compared with valsartan, treatment with sacubitril/valsartan did not improve the clinical composite of number of days alive, out of hospital, and free from heart failure events. Aside from a statistically significant increase in non-life-threatening hyperkalemia in the sacubitril/valsartan arm (28 [17%] vs 15 [9%]; P = .04), there were no observed safety concerns. Conclusions and Relevance: The findings of this trial showed that, in patients with chronic advanced heart failure with a reduced ejection fraction, there was no statistically significant difference between sacubitril/valsartan and valsartan with respect to reducing NT-proBNP levels. Trial Registration: ClinicalTrials.gov Identifier: NCT02816736.
Authors: Daniela Tomasoni; Julie K K Vishram-Nielsen; Matteo Pagnesi; Marianna Adamo; Carlo Mario Lombardi; Finn Gustafsson; Marco Metra Journal: ESC Heart Fail Date: 2022-03-30
Authors: Birju R Rao; Candace D Speight; Larry A Allen; Scott D Halpern; Yi-An Ko; Daniel D Matlock; Miranda A Moore; Alanna A Morris; Laura D Scherer; Mary C Thomson; Peter Ubel; Neal W Dickert Journal: J Am Heart Assoc Date: 2022-06-20 Impact factor: 6.106
Authors: Andrew P Sindone; Carmine De Pasquale; John Amerena; Christine Burdeniuk; Alicia Chan; Andrew Coats; David L Hare; Peter Macdonald; Aaron Sverdlov; John J Atherton Journal: Med J Aust Date: 2022-07-31 Impact factor: 12.776