Abstract
Background: Sacubitril/valsartan is an angiotensin receptor–neprilysin inhibitor indicated for the treatment of patients with chronic heart failure (HF) with reduced ejection fraction; however, its mechanism of benefit remains unclear. Biomarkers that are linked to ventricular remodeling, myocardial injury, and fibrosis may provide mechanistic insight and important clinical guidance regarding sacubitril/valsartan use. Methods: This 52-week, multicenter, open-label, single-arm study is designed to (1) correlate biomarker changes with cardiac remodeling parameters, cardiovascular outcomes, and patient-reported outcome data and (2) determine short- and long-term changes in concentrations of biomarkers related to potential mechanisms of action and effects of sacubitril/valsartan therapy. Approximately 830 patients with HF with reduced ejection fraction will be initiated and titrated on sacubitril/valsartan according to United States prescribing information. Primary efficacy end points include the changes in N-terminal pro–B-type natriuretic peptide concentrations and cardiac remodeling from baseline to 1 year. Secondary end points include changes in concentrations of N-terminal pro–B-type natriuretic peptide and remodeling to 6 months, and changes in patient-reported outcomes using the Kansas City Cardiomyopathy Questionnaire-23 from baseline to 1 year. In addition, several other relevant biomarkers will be measured. Biomarker changes relative to the number of cardiovascular events in 12 months will also be assessed as exploratory end points. Conclusions: Results from the Prospective Study of Biomarkers, Symptom Improvement, and Ventricular Remodeling During Sacubitril/Valsartan Therapy for Heart Failure (PROVE-HF) will help establish a mechanistic understanding of angiotensin receptor–neprilysin inhibitor therapeutic benefits and provide clinicians with clarity on how to interpret information on biomarkers during treatment (PROVE-HF ClinicalTrials.gov identifier: NCT02887183).
| Original language | English (US) |
|---|---|
| Pages (from-to) | 130-136 |
| Number of pages | 7 |
| Journal | American Heart Journal |
| Volume | 199 |
| DOIs | |
| State | Published - May 1 2018 |
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ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
Cite this
Rationale and methods of the Prospective Study of Biomarkers, Symptom Improvement, and Ventricular Remodeling During Sacubitril/Valsartan Therapy for Heart Failure (PROVE-HF). / Januzzi, James L.; Butler, Javed; Fombu, Emmanuel; Maisel, Alan; McCague, Kevin; Pina, Ileana L.; Prescott, Margaret F.; Riebman, Jerome B.; Solomon, Scott.
In: American Heart Journal, Vol. 199, 01.05.2018, p. 130-136.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Rationale and methods of the Prospective Study of Biomarkers, Symptom Improvement, and Ventricular Remodeling During Sacubitril/Valsartan Therapy for Heart Failure (PROVE-HF)
AU - Januzzi, James L.
AU - Butler, Javed
AU - Fombu, Emmanuel
AU - Maisel, Alan
AU - McCague, Kevin
AU - Pina, Ileana L.
AU - Prescott, Margaret F.
AU - Riebman, Jerome B.
AU - Solomon, Scott
PY - 2018/5/1
Y1 - 2018/5/1
N2 - Background: Sacubitril/valsartan is an angiotensin receptor–neprilysin inhibitor indicated for the treatment of patients with chronic heart failure (HF) with reduced ejection fraction; however, its mechanism of benefit remains unclear. Biomarkers that are linked to ventricular remodeling, myocardial injury, and fibrosis may provide mechanistic insight and important clinical guidance regarding sacubitril/valsartan use. Methods: This 52-week, multicenter, open-label, single-arm study is designed to (1) correlate biomarker changes with cardiac remodeling parameters, cardiovascular outcomes, and patient-reported outcome data and (2) determine short- and long-term changes in concentrations of biomarkers related to potential mechanisms of action and effects of sacubitril/valsartan therapy. Approximately 830 patients with HF with reduced ejection fraction will be initiated and titrated on sacubitril/valsartan according to United States prescribing information. Primary efficacy end points include the changes in N-terminal pro–B-type natriuretic peptide concentrations and cardiac remodeling from baseline to 1 year. Secondary end points include changes in concentrations of N-terminal pro–B-type natriuretic peptide and remodeling to 6 months, and changes in patient-reported outcomes using the Kansas City Cardiomyopathy Questionnaire-23 from baseline to 1 year. In addition, several other relevant biomarkers will be measured. Biomarker changes relative to the number of cardiovascular events in 12 months will also be assessed as exploratory end points. Conclusions: Results from the Prospective Study of Biomarkers, Symptom Improvement, and Ventricular Remodeling During Sacubitril/Valsartan Therapy for Heart Failure (PROVE-HF) will help establish a mechanistic understanding of angiotensin receptor–neprilysin inhibitor therapeutic benefits and provide clinicians with clarity on how to interpret information on biomarkers during treatment (PROVE-HF ClinicalTrials.gov identifier: NCT02887183).
AB - Background: Sacubitril/valsartan is an angiotensin receptor–neprilysin inhibitor indicated for the treatment of patients with chronic heart failure (HF) with reduced ejection fraction; however, its mechanism of benefit remains unclear. Biomarkers that are linked to ventricular remodeling, myocardial injury, and fibrosis may provide mechanistic insight and important clinical guidance regarding sacubitril/valsartan use. Methods: This 52-week, multicenter, open-label, single-arm study is designed to (1) correlate biomarker changes with cardiac remodeling parameters, cardiovascular outcomes, and patient-reported outcome data and (2) determine short- and long-term changes in concentrations of biomarkers related to potential mechanisms of action and effects of sacubitril/valsartan therapy. Approximately 830 patients with HF with reduced ejection fraction will be initiated and titrated on sacubitril/valsartan according to United States prescribing information. Primary efficacy end points include the changes in N-terminal pro–B-type natriuretic peptide concentrations and cardiac remodeling from baseline to 1 year. Secondary end points include changes in concentrations of N-terminal pro–B-type natriuretic peptide and remodeling to 6 months, and changes in patient-reported outcomes using the Kansas City Cardiomyopathy Questionnaire-23 from baseline to 1 year. In addition, several other relevant biomarkers will be measured. Biomarker changes relative to the number of cardiovascular events in 12 months will also be assessed as exploratory end points. Conclusions: Results from the Prospective Study of Biomarkers, Symptom Improvement, and Ventricular Remodeling During Sacubitril/Valsartan Therapy for Heart Failure (PROVE-HF) will help establish a mechanistic understanding of angiotensin receptor–neprilysin inhibitor therapeutic benefits and provide clinicians with clarity on how to interpret information on biomarkers during treatment (PROVE-HF ClinicalTrials.gov identifier: NCT02887183).
UR - http://www.scopus.com/inward/record.url?scp=85043467903&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85043467903&partnerID=8YFLogxK
U2 - 10.1016/j.ahj.2017.12.021
DO - 10.1016/j.ahj.2017.12.021
M3 - Article
C2 - 29754651
AN - SCOPUS:85043467903
VL - 199
SP - 130
EP - 136
JO - American Heart Journal
JF - American Heart Journal
SN - 0002-8703
ER -