Eric J Velazquez1, David A Morrow2, Adam D DeVore3, Andrew P Ambrosy3, Carol I Duffy4, Kevin McCague4, Adrian F Hernandez3, Ricardo A Rocha4, Eugene Braunwald2. 1. Duke Clinical Research Institute, Duke University, Durham, NC. Electronic address: eric.velazquez@duke.edu. 2. Thrombolysis in Myocardial Infarction (TIMI) Study Group, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA. 3. Duke Clinical Research Institute, Duke University, Durham, NC. 4. Novartis Pharmaceuticals Corporation, East Hanover, NJ.
Abstract
OBJECTIVE: The objective is to assess the safety, tolerability, and efficacy of sacubitril/valsartan compared with enalapril in patients with heart failure (HF) with a reduced ejection fraction (EF) stabilized during hospitalization for acute decompensated HF. BACKGROUND:Sacubitril/valsartan, a first-in-class angiotensin receptor-neprilysin inhibitor, improves survival among ambulatory HF patients with a reduced EF. However, there is very limited experience with the in-hospital initiation of sacubitril/valsartan in patients who have been stabilized following hospitalization for acute decompensated HF. METHODS: PIONEER-HF is a 12-week, prospective, multicenter, double-blind, randomized controlled trial enrolling a planned 882 patients at more than 100 participating sites in the United States. Medically stable patients >18 years of age with an EF <40% and an amino terminal-pro b-type natriuretic peptide >1600 pg/mL or b-type natriuretic peptide >400 pg/mL are eligible for participation no earlier than 24 hours and up to 10 days from initial presentation while still hospitalized. Patients are randomly assigned 1:1 to in-hospital initiation of sacubitril/valsartan titrated to 97/103 mg by mouth twice daily versus enalapril titrated to 10 mg by mouth twice daily for 8 weeks. All patients receive open-label treatment with sacubitril/valsartan for the remaining 4 weeks of the study. The primary efficacy end point is the time-averaged proportional change in amino terminal-pro b-type natriuretic peptide from baseline through weeks 4 and 8. Secondary and exploratory end points include serum and urinary biomarkers as well as clinical outcomes. Safety end points include the incidence of angioedema, hypotension, renal insufficiency, and hyperkalemia. CONCLUSION: The PIONEER-HF trial will inform clinical practice by providing evidence on the safety, tolerability, and efficacy of in-hospital initiation of sacubitril/valsartan among patients who have been stabilized following an admission for acute decompensated HF with a reduced EF.
RCT Entities:
OBJECTIVE: The objective is to assess the safety, tolerability, and efficacy of sacubitril/valsartan compared with enalapril in patients with heart failure (HF) with a reduced ejection fraction (EF) stabilized during hospitalization for acute decompensated HF. BACKGROUND:Sacubitril/valsartan, a first-in-class angiotensin receptor-neprilysin inhibitor, improves survival among ambulatory HF patients with a reduced EF. However, there is very limited experience with the in-hospital initiation of sacubitril/valsartan in patients who have been stabilized following hospitalization for acute decompensated HF. METHODS: PIONEER-HF is a 12-week, prospective, multicenter, double-blind, randomized controlled trial enrolling a planned 882 patients at more than 100 participating sites in the United States. Medically stable patients >18 years of age with an EF <40% and an amino terminal-pro b-type natriuretic peptide >1600 pg/mL or b-type natriuretic peptide >400 pg/mL are eligible for participation no earlier than 24 hours and up to 10 days from initial presentation while still hospitalized. Patients are randomly assigned 1:1 to in-hospital initiation of sacubitril/valsartan titrated to 97/103 mg by mouth twice daily versus enalapril titrated to 10 mg by mouth twice daily for 8 weeks. All patients receive open-label treatment with sacubitril/valsartan for the remaining 4 weeks of the study. The primary efficacy end point is the time-averaged proportional change in amino terminal-pro b-type natriuretic peptide from baseline through weeks 4 and 8. Secondary and exploratory end points include serum and urinary biomarkers as well as clinical outcomes. Safety end points include the incidence of angioedema, hypotension, renal insufficiency, and hyperkalemia. CONCLUSION: The PIONEER-HF trial will inform clinical practice by providing evidence on the safety, tolerability, and efficacy of in-hospital initiation of sacubitril/valsartan among patients who have been stabilized following an admission for acute decompensated HF with a reduced EF.
Authors: Elena-Laura Antohi; Andrew P Ambrosy; Sean P Collins; Ali Ahmed; Vlad Anton Iliescu; Gad Cotter; Peter S Pang; Javed Butler; Ovidiu Chioncel Journal: Am J Ther Date: 2019 Mar/Apr Impact factor: 2.688
Authors: David D Berg; Eugene Braunwald; Adam D DeVore; Anuradha Lala; Sean P Pinney; Carol I Duffy; Yared Gurmu; Eric J Velazquez; David A Morrow Journal: JACC Heart Fail Date: 2020-08-12 Impact factor: 12.035
Authors: Adam D DeVore; Eugene Braunwald; David A Morrow; Carol I Duffy; Andrew P Ambrosy; Hrishikesh Chakraborty; Kevin McCague; Ricardo Rocha; Eric J Velazquez Journal: JAMA Cardiol Date: 2020-02-01 Impact factor: 14.676
Authors: Marat Fudim; Sabina Sayeed; Haolin Xu; Roland A Matsouaka; Paul A Heidenreich; Eric J Velazquez; Clyde W Yancy; Gregg C Fonarow; Adrian F Hernandez; Adam D DeVore Journal: Circ Heart Fail Date: 2020-04-06 Impact factor: 8.790