Rationale and methods of the Prospective Study of Biomarkers, Symptom Improvement, and Ventricular Remodeling During Sacubitril/Valsartan Therapy for Heart Failure (PROVE-HF).

Autor: Januzzi JL; Massachusetts General Hospital, Boston, MA; Baim Institute for Clinical Research, Boston, MA. Electronic address: JJanuzzi@partners.org., Butler J; Health Institute, Stony Brook University, Stony Brook, NY., Fombu E; Novartis Pharmaceuticals, East Hanover, NJ., Maisel A; University of California, San Diego School of Medicine, San Diego, CA., McCague K; Novartis Pharmaceuticals, East Hanover, NJ., Piña IL; Montefiore Medical Center, Bronx, NY., Prescott MF; Novartis Pharmaceuticals, East Hanover, NJ., Riebman JB; Novartis Pharmaceuticals, East Hanover, NJ., Solomon S; Harvard Medical School, Brigham and Women's Hospital, Boston, MA.
Jazyk: angličtina
Zdroj: American heart journal [Am Heart J] 2018 May; Vol. 199, pp. 130-136. Date of Electronic Publication: 2018 Feb 13.
DOI: 10.1016/j.ahj.2017.12.021
Abstrakt: 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).
(Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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