Ejection Fraction, Biomarkers, and Outcomes and Impact of Vericiguat on Outcomes Across EF in VICTORIA.

Background: Vericiguat reduced the risk of cardiovascular death (CVD) or hospitalization for heart failure (HF) in patients with worsening HF and reduced left ventricular ejection fraction (LVEF).
Objectives: The authors assessed the association of LVEF with biomarker levels, risk of outcome, and whether the effect of vericiguat was homogeneous across LVEF in the VICTORIA (Vericiguat Global Study in Subjects with Heart Failure With Reduced Ejection Fraction) trial.
Methods: Patients were grouped by LVEF tertiles (≤24%, 25%-33%, and >33%). Patient characteristics, clinical outcomes, and efficacy and safety of vericiguat were examined by tertile. Prespecified biomarkers including N-terminal pro-B-type natriuretic peptide, cardiac troponin T, growth differentiation factor 15, interleukin 6, high-sensitivity C-reactive protein, and cystatin C were examined.
Results: The mean LVEF was 29% ± 8% (range: 5%-45%). A pattern of higher N-terminal pro-B-type natriuretic peptide, high-sensitivity C-reactive protein, and interleukin 6 was evident in patients in the lowest LVEF tertile vs the other tertiles. Patients with lower LVEF experienced higher rates of the composite outcome (41.7%, 36.3%, and 33.4% for LVEF ≤24, 25-33, and >33; P < 0.001). There was no significant treatment effect heterogeneity of vericiguat across LVEF groups (adjusted HR from lowest to highest tertiles: 0.79 [95% CI: 0.68-0.94]; 0.95 [95% CI: 0.82-1.11]; 0.94 [95% CI: 0.79-1.11]; P for interaction = 0.222), although the HR was numerically lower in the lowest tertile. There was also no heterogeneity of effect for CVD and HF hospitalization individually (P interaction for CVD = 0.964; HF hospitalization = 0.438). Discontinuation of treatment because of adverse events, symptomatic hypotension, or syncope was consistent across the range of LVEF.
Conclusions: Patients with lower LVEF had a distinctive biomarker profile and a higher risk for adverse clinical outcomes vs those with a higher LVEF. There was no significant interaction for the benefit of vericiguat across LVEF tertiles, although the largest signal for benefit in both the primary outcome and HF hospitalizations was noted in tertile 1 (LVEF ≤24%). (Vericiguat Global Study in Subjects with Heart Failure With Reduced Ejection Fraction [VICTORIA]; NCT02861534).
Competing Interests: Funding Support and Author Disclosures The VICTORIA trial was funded by Merck Sharp and Dohme Corp, a subsidiary of Merck and Co Inc, and Bayer AG. Dr Butler has received consulting fees from Abbott, Adrenomed, Amgen, Array, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CVRx, G3 Pharmaceutical, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, Novo Nordisk, Roche, and Vifor. Dr Lund is a consultant for Bayer/Merck; has received grants unrelated to the present work from AstraZeneca, Vifor, Boston Scientific, Boehringer Ingelheim, and Novartis; has received consulting fees from Merck, Vifor, AstraZeneca, Bayer, Pharmacosmos, MedScape, Sanofi, Lexicon, Myokardia, Boehringer Ingelheim, and Servier; has received speaker honoraria from Abbott, MedScape, Radcliffe, AstraZeneca, Novartis, and patent AnaCardio; and has stock ownership in AnaCardio. Dr deFilippi has received institutional research grants from Abbott Diagnostics, Roche Diagnostics, Siemens Healthineers, and Ortho Diagnostics; and has received consulting fees from FujiRebio, Roche Diagnostics, Siemens Healthineers, and Ortho Diagnostics. Dr Blaustein is an employee of Merck and Co, Inc. Mr Ezekowitz has received research grants and consulting fees from Bayer, Merck, Servier, Amgen Sanofi, Novartis, Cytokinetics, American Regent, and Applied Therapeutics. Dr Freitas is an employee of Bayer AG. Dr Hernandez has received research grants from Merck, AstraZeneca, Novartis, and Verily; and has received honoraria from Merck, Bayer, Amgen, AstraZeneca, and Novartis. Dr O’Connor has received research grants from Merck; and has received consulting fees from Bayer, Dey LP, and Bristol Myers Squibb Foundation. Dr Voors has received research grants from Boehringer Ingelheim and Roche Diagnostics; and has received consulting fees from Merck, Bayer, Amgen, AstraZeneca, Boehringer Ingelheim, Cytokinetics, Myokardia, Novartis, Servier, and Roche Diagnostics. Dr Westerhout has received consulting fees from Bayer. Dr Lam has received research grants from Bayer and Roche Diagnostics; has received consulting fees from Abbott, Actelion, Alleviant Medical, Allysta Pharma, Amgen, AnaCardio AB, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Darma Inc, EchoNous Inc, Impulse Dynamics, Ionis Pharmaceutical, Janssen Research and Development LLC, Medscape/WebMD Global LLC, Merck, Novartis, Novo Nordisk, Prosciento Inc, Radcliffe Group Ltd, Roche Diagnostics, Sanofi, Siemens Healthcare Diagnostics, and Us2.ai; and is a cofounder and nonexecutive director of Us2.ai. Dr Armstrong has received research grants from Merck, Bayer, Sanofi-Aventis Recherche and Développement, Boehringer Ingelheim, and CSL Limited; and has received consulting fees from Merck, Bayer, AstraZeneca, and Novartis.
(Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)