Evolution of NT-proBNP During Prerandomization Screening in VICTORIA: Implications for Clinical Outcomes and Efficacy of Vericiguat

Paul W Armstrong; Yinggan Zheng; Lars H Lund; Javed Butler; Richard W Troughton; Michele Emdin; Carolyn S P Lam; Piotr Ponikowski; Robert O Blaustein; Christopher M O'Connor; Lothar Roessig; Adriaan A Voors; Justin A Ezekowitz; Cynthia M Westerhout; VICTORIA Study Group

doi:10.1161/CIRCHEARTFAILURE.123.010661

Evolution of NT-proBNP During Prerandomization Screening in VICTORIA: Implications for Clinical Outcomes and Efficacy of Vericiguat

Circ Heart Fail. 2023 Oct;16(10):e010661. doi: 10.1161/CIRCHEARTFAILURE.123.010661. Epub 2023 Jul 28.

Authors

Affiliations

¹ Canadian VIGOUR Centre, University of Alberta, Edmonton, AB, Canada (P.W.A., Y.Z., J.A.E., C.M.W.).
² Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden (L.H.L.).
³ Baylor Scott and White Research Institute, Dallas, TX (J.B.).
⁴ University of Otago, Christchurch, New Zealand (R.W.T.).
⁵ Health Science Interdisciplinary Center, Scuola Superiore Sant'Anna, Pisa, Italy (M.E.).
⁶ National Heart Centre Singapore and Duke-National University of Singapore (C.S.P.L.).
⁷ Wroclaw Medical University, Poland (P.P.).
⁸ Merck & Co Inc, Rahway, NJ (R.O.B.).
⁹ Innova Heart and Vascular Institute, Falls Church, VA (C.M.O.).
¹⁰ Bayer AG, Wuppertal, Germany (L.R.).
¹¹ Department of Cardiology, University of Groningen, University Medical Center of Groningen, the Netherlands (A.A.V.).

PMID: 37503602
DOI: 10.1161/CIRCHEARTFAILURE.123.010661

Abstract

Background: Selecting high-risk patients with heart failure with potentially modifiable cardiovascular events is a priority. Our objective was to evaluate NT-proBNP (N-terminal pro-B-type natriuretic peptide) changes during a 30-day screening to establish (1) the frequency and direction of changes; (2) whether a relationship exists between changes in NT-proBNP and the primary composite outcome of cardiovascular death and heart failure hospitalization; and (3) whether changes in NT-proBNP relate to vericiguat's clinical benefit.

Methods: VICTORIA (A Study of Vericiguat in Participants With Heart Failure With Reduced Ejection Fraction) randomized 5050 patients with heart failure with reduced ejection fraction and a recent worsening heart failure event. We studied 3821 patients who had NT-proBNP measured during screening and at randomization.

Results: Sixteen hundred exhibited a >20% reduction, 1412 had ≤20% change, and 809 showed a >20% rise in NT-proBNP levels. As compared with the primary composite outcome of 28.4/100 patient-years (497 events; 31.1%) in patients with a >20% decline in NT-proBNP, those with >20% during screening had worse outcomes; 48.8/100 patient-years (359 events; 44.4%); adjusted hazard ratio, 1.61 (95% CI, 1.39-1.85). Those patients with a ≤20% change in NT-proBNP had intermediate outcomes; 39.2/100 patient-years (564 events; 39.9%); adjusted hazard ratio, 1.33 (95% CI, 1.17-1.51). No relationship existed between NT-proBNP changes during screening and vericiguat's effect on cardiovascular death and heart failure hospitalization.

Conclusions: Substantial differences occurred in the rates of cardiovascular death and heart failure hospitalization, especially in patients with a >20% change in NT-proBNP levels during screening interval. Sequential NT-proBNP levels add important prognostic information meriting consideration in future heart failure trials.

Registration: URL: https://www.

Clinicaltrials: gov; Unique identifier: NCT02861534.

Keywords: clinical trial; heart failure; hospitalization; natriuretic peptides; screening.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers
Heart Failure* / diagnosis
Humans
Natriuretic Peptide, Brain
Peptide Fragments
Prognosis
Stroke Volume
Ventricular Dysfunction, Left*

Substances

pro-brain natriuretic peptide (1-76)
Natriuretic Peptide, Brain
vericiguat
Peptide Fragments
Biomarkers

Associated data

ClinicalTrials.gov/NCT02861534