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Meta-Analysis
. 2022 Dec;9(6):3791-3803.
doi: 10.1002/ehf2.14050. Epub 2022 Jul 26.

Vericiguat and NT-proBNP in patients with heart failure with reduced ejection fraction: analyses from the VICTORIA trial

Michele Senni  1 , Jose Lopez-Sendon  2 , Alain Cohen-Solal  3 , Piotr Ponikowski  4 , Richard Nkulikiyinka  5 , Cecilia Freitas  6 , Vanja Miodrag Vlajnic  7 , Lothar Roessig  5 , Burkert Pieske  8
Affiliations
Meta-Analysis

Vericiguat and NT-proBNP in patients with heart failure with reduced ejection fraction: analyses from the VICTORIA trial

Michele Senni et al. ESC Heart Fail. 2022 Dec.

Abstract

Aims: Treatment response to vericiguat, based on baseline N-terminal pro-brain natriuretic peptide (NT-proBNP) subgroups specified in the protocol, was evaluated in the heart failure (HF) VICTORIA trial population by post hoc analysis of combined lower three quartiles [Q1-Q3] vs. the upper quartile [Q4].

Methods and results: VICTORIA participants with available baseline NT-proBNP levels (n = 4805; 95.1% of total) were included. Compared with patients in Q1-Q3 (NT-proBNP: Q1, ≤1556 pg/mL; Q2, >1556-2816 pg/mL; and Q3, >2816-5314 pg/mL), patients in Q4 (NT-proBNP: >5314 pg/mL) were older (69.2 ± 12.0 vs. 66.6 ± 12.1 years), had lower mean ejection fraction (27.2 ± 8.3% vs. 29.5 ± 8.2%; P < 0.0001), and were more likely to be in New York Heart Association (NYHA) Class III (51.8 vs. 35.6%) or IV (2.4 vs. 1.0%). Compared with Q1-Q3, patients in Q4 had higher mean Meta-Analysis Global Group in Chronic Heart Failure risk score (27.3 ± 6.6 vs. 23.5 ± 6.4; P < 0.0001), had lower mean estimated glomerular filtration rate (eGFR; 51.5 ± 25.5 vs. 65.0 ± 26.8 mL/min/1.73 m2 ; P < 0.0001) and haemoglobin (12.8 ± 2.0 vs. 13.6 ± 1.9 g/dL; P < 0.0001), and more had atrial fibrillation (48.7% vs. 43.1%; P = 0.0007) and were randomized while hospitalized for HF (14.8 vs. 9.9%; P < 0.0001). Target dose was achieved in 72.3 and 63.7% of patients in Q1-Q3 and Q4, respectively (P < 0.0001). Primary outcome (composite of time to cardiovascular death or first HF hospitalization) rates were 24.5 and 31.7 per 100 patient-years for vericiguat and placebo in Q1-Q3 [hazard ratio (HR) 0.78; 95% confidence interval (CI) 0.69-0.88, P < 0.001] and 73.6 and 63.6 in Q4 (HR 1.15; 95% CI 0.99-1.34, P = 0.070). Serious adverse events were more frequent in NT-proBNP Q4 (total population) compared with Q1-Q3 (38.3 vs. 32.3%; P = 0.0001), driven mainly by the placebo group. Adverse events leading to death were more frequent in Q4 than Q1-Q3 (5.8 vs. 2.4%; P < 0.0001).

Conclusions: Plasma NT-proBNP may help identify patients with worsening HF with reduced ejection fraction, in whom the beneficial effects of vericiguat may be highest. Patients with highest NT-proBNP values are probably too far advanced, suffering more co-morbidities, or still clinically unstable after decompensation to derive benefit from vericiguat.

Trial registration: ClinicalTrials.gov NCT02861534.

Keywords: Heart failure; Heart failure with reduced ejection fraction; NT-proBNP.

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Conflict of interest statement

RN, CF, VMV, and LR are employees of Bayer AG and may own stock in the company. ACS has received honoraria from Bayer AG and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD), during the conduct of the study; and personal fees from Novartis, Abbott, Sanofi, Vifor, Astra Zeneca, Servier, Leo Pharma, and Boehringer Ingelheim, outside the submitted work. JLS has received research grants from MSD, Angem, Pfizer, and Bayer AG; honoraria from Menarini; support for attending meetings from Pfizer; and support for participation on advisory boards from Bayer AG. MS has received consulting fees from Bayer AG and MSD. PP has received consulting fees from Boehringer Ingelheim, AstraZeneca, Vifor Pharma, Amgen, Servier, Novartis, Bayer, MSD, Pfizer, Cibiem, Impulse Dynamics, Renal Guard Solutions, and BMS. PP has also received honoraria from Boehringer Ingelheim, AstraZeneca, Vifor Pharma, Amgen, Servier, Novartis, Berlin Chemie, Bayer, Pfizer, Impulse Dynamics, Renal Guard Solutions, BMS, and Abbott Vascular for lectures, presentations, speakers' bureaus, manuscript writing, or educational events. BP has received research funds from Bayer Healthcare, Servier, and AstraZeneca, as well as speakers honoraria/committee membership fees from Novartis, Bayer Healthcare, Daiichi‐Sankyo, MSD, Stealth Peptides, AstraZeneca, Sanofi, Vifor, and Servier.

Figures

Figure 1
Figure 1
Kaplan–Meier curves of clinical outcomes for the primary composite endpoint and its components in patients with baseline NT‐proBNP levels in Quartiles 1–3 (Q1–Q3) and Quartile 4 (Q4). Primary outcome was composite of death from cardiovascular causes or first hospitalization for HF. Cumulative incidences of composite endpoint by NT‐proBNP group (Q1–Q3 and Q4) are shown in Panels A and B, respectively. Cumulative incidences of cardiovascular death by NT‐proBNP group (Q1–Q3 and Q4) are shown in Panels C and D, respectively. Cumulative incidences of first hospitalization by NT‐proBNP group (Q1–Q3 and Q4) are shown in Panels E and F, respectively. CI, confidence interval; CV, cardiovascular; HF, heart failure; NT‐proBNP, N‐terminal pro‐brain natriuretic peptide.
Figure 2
Figure 2
Forest plot of hazard ratios with 95% confidence intervals are shown for the primary composite endpoint and its components, CV death and time to first HF hospitalization, as well as total HF hospitalization, CV hospitalization, and all‐cause mortality, in patients with baseline NT‐proBNP levels in Quartiles 1–3 (Q1–Q3) and Quartile 4 (Q4). CI, confidence interval; CV, cardiovascular; HF, heart failure; HFH, heart failure hospitalization; HR, hazard ratio; NT‐proBNP, N‐terminal pro‐brain natriuretic peptide. *Calculated using the Anderson–Gill model.
See this image and copyright information in PMC

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