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. 2023 Feb;11(2):211-223.
doi: 10.1016/j.jchf.2022.11.007.

Applicability of Vericiguat to Patients Hospitalized for Heart Failure in the United States

Muhammad Shahzeb Khan  1 , Haolin Xu  2 , Gregg C Fonarow  3 , Dominik Lautsch  4 , Robert Hilkert  4 , Larry A Allen  5 , Adam D DeVore  6 , Brooke Alhanti  2 , Clyde W Yancy  7 , Nancy M Albert  8 , Javed Butler  9 , Stephen J Greene  10
Affiliations

Applicability of Vericiguat to Patients Hospitalized for Heart Failure in the United States

Muhammad Shahzeb Khan et al. JACC Heart Fail. 2023 Feb.

Abstract

Background: In January 2021, vericiguat, a soluble guanylate cyclase stimulator, was approved by the U.S. Food and Drug Administration (FDA) to reduce the risk of cardiovascular death and heart failure (HF) hospitalization among patients with a recent worsening HF event based on the VICTORIA (VerICiguaT Global Study in Subjects with Heart Failure with Reduced Ejection Fraction) trial.

Objectives: This study sought to leverage a contemporary U.S. registry of patients hospitalized for heart failure (HF) to characterize patients who may be candidates for vericiguat based on FDA label and the VICTORIA trial eligibility criteria.

Methods: The authors studied patients hospitalized for HF with ejection fraction (EF) <45% across 525 sites in the GWTG-HF (Get With The Guidelines-Heart Failure) registry between January 2014 and December 2020. Approximate FDA label criteria (excluding estimated glomerular filtration rate [eGFR] <15 mL/min/1.73 m2, dialysis, or patients with heart transplantation or durable mechanical circulatory support) and eligibility criteria for the VICTORIA trial were applied to the GWTG-HF cohort.

Results: Among 241,057 patients with EF <45% in the GWTG-HF registry, 221,730 (92%) could be candidates for vericiguat under the FDA label and 92,249 (38%) would have been eligible for the VICTORIA trial. The most frequent reasons for ineligibility for the FDA label were eGFR <15 mL/min/1.73 m2 (5.7%) and dialysis (1.6%). Although there were greater proportions of women and Black patients in the GWTG-HF registry, most clinical characteristics were qualitatively similar with patients enrolled in the VICTORIA trial. Among Medicare beneficiaries in the GWTG-HF registry eligible for vericiguat by either FDA label or VICTORIA trial criteria, 12-month postdischarge rates of mortality (36%-37%), HF hospitalization (33%-35%), all-cause hospitalization (64%-66%), and mean health care expenditure (U.S. $25,106-$25,428) were high.

Conclusions: Data from a large, contemporary U.S. registry of patients actively hospitalized for HF with EF <45% suggest that approximately 4 in 10 patients meet the criteria of the VICTORIA trial and that more than 9 in 10 patients are potential candidates for vericiguat based on the FDA label. Contemporary Medicare beneficiaries hospitalized for HF with EF <45% and eligible for vericiguat face high rates of postdischarge mortality and readmission and accrue substantial health care costs.

Keywords: heart failure; hospitalization; trial; vericiguat.

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Conflict of interest statement

Funding Support and Author Disclosures This study was supported by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc (Rahway, New Jersey, USA). The Get With The Guidelines–Heart Failure program is provided by the American Heart Association and sponsored, in part, by Novartis, Boehringer Ingelheim and Eli Lilly Diabetes Alliance, Novo Nordisk, Sanofi, AstraZeneca, and Bayer. Dr Fonarow has served as a consultant for Abbott, Amgen, AstraZeneca, Bayer, Cytokinetics, Janssen, Medtronic, Merck Sharp & Dohme LLC (a subsidiary of Merck & Co, Inc), and Novartis. Drs Lautsch and Hilkert are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc. Dr Allen has received grant support from the National Institutes of Health and Patient-Centered Outcomes Research Institute; and has received consulting fees from ACI Clinical, American Heart Association, Boston Scientific, Cytokinetics, Novartis, and UpToDate. Dr Albert has received grant support from Novartis and AstraZeneca; and consulting fees from Boston Scientific, Boehringer Ingelheim/Lilly, Cytokinetics, and Merck Sharp & Dohme LLC (a subsidiary of Merck & Co, Inc). Dr Butler has served as a consultant for Abbott, Adrenomed, Arena Pharma, Array, Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Cardior, CVRx, Eli Lilly, G3 Pharma, Imbria, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck Sharp & Dohme LLC (a subsidiary of Merck & Co, Inc), Novartis, Novo Nordisk, Sequana Medical, V-Wave Limited, and Vifor. Dr Greene has received research support from the Duke University Department of Medicine Chair’s Research Award, American Heart Association (#929502), National Heart, Lung, and Blood Institute, Amgen, AstraZeneca, Bristol Myers Squibb, Cytokinetics, Merck Sharp & Dohme LLC (a subsidiary of Merck & Co, Inc), Novartis, Pfizer, and Sanofi; served on the advisory board for Amgen, AstraZeneca, Boehringer Ingelheim/Lilly, Bristol Myers Squibb, Cytokinetics, Roche Diagnostics, scPharmaceuticals, and Sanofi; and served as a consultant for Amgen, Bayer, Boehringer Ingelheim/Lilly, Bristol Myers Squibb, CSL Vifor, Corteria Therapeutics, Merck Sharp & Dohme LLC (a subsidiary of Merck & Co, Inc), PharmaIN, Roche Diagnostics, Sanofi, Tricog Health, and Urovant Pharmaceuticals; and has received speaker fees from Boehringer Ingelheim and Cytokinetics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

Figure 1.
Figure 1.. Identifying the Proportion of Patients Hospitalized for Heart Failure with Ejection Fraction <45% that are Candidates for Initiation of Vericiguat in the Get With The Guidelines-Heart Failure Registry.
BNP=B-type natriuretic peptide; CABG=coronary artery bypass grafting; eGFR=estimated glomerular filtration rate; FDA=Food and Drug Administration; HF=heart failure; LVEF=left ventricular ejection fraction; NT-proBNP, N-terminal pro-B-type natriuretic peptide; PCI=percutaneous coronary intervention; SBP=systolic blood pressure
Figure 2.
Figure 2.. Background Medical Therapy in the VICTORIA Trial and GWTG-HF Registry.
Shows the medications by VICTORIA eligible patients, FDA label patients, hospitalized HF with EF <45% population, and VICTORIA randomized trial population. Percentages represent proportion of patients prescribed these medications at discharge among all groups except VICTORA trial population where the percentages represent the proportion of patients who were on these medications at baseline.
Figure 3.
Figure 3.. Post-discharge Outcomes of Heart Failure Patients Eligible for Vericiguat.
Shows the cumulative incidence plots of all-cause mortality, all cause readmission and heart failure admission for the 3 cohorts: hospitalized HF with EF<45% population, FDA label and VICTORIA eligible patients. The 3 cohorts are represented by red, blue and green colors respectively.
Figure 4.
Figure 4.. Healthcare Expenditure of Heart Failure Patients Eligible for Vericiguat.
Graph depicts cumulative costs in each patient group divided by number of patients at risk at that timepoint accounting for competing risk of death. Mean per-patient cost over 12-months post-discharge are shown for the hospitalized HF with EF<45% population (blue), FDA label patients (red), and VICTORIA eligible patients (black), respectively.
Central Illustration.
Central Illustration.. Applicability of Vericiguat to US Patients Hospitalized for HF with EF<45%.
Clinical characteristics, clinical outcomes, and clinical outcomes among VICTORIA eligible patients, FDA label patients, the hospitalized HF with EF <45% population in GWTG-HF, as well as patients enrolled in the VICTORIA randomized trial. ARNI=Angiotensin receptor neprilysin inhibitor; ARB= Angiotensin receptor blocker; ACEI= Angiotensin converting enzyme inhibitor.
See this image and copyright information in PMC

Comment in

References

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