Vericiguat for the treatment of heart failure with reduced ejection fraction

ABSTRACT

Introduction

Despite significant therapeutic advancements in heart failure with reduced ejection fraction (HFrEF), the residual risk of all-cause mortality and hospitalizations remains high among patients with HFrEF. Vericiguat is a novel oral soluble guanylate cyclase (sGC) stimulator which was approved by the US Food and Drug administration (FDA) in January 2021 for use in patients with symptomatic chronic HF and an ejection fraction less than 45% following a hospitalization for HF or the need for outpatient intravenous diuretics.

Areas covered

We provide a concise review of the pharmacology, clinical efficacy, and tolerability of vericiguat in HFrEF. We also discuss the role of vericiguat in current clinical practice.

Expert opinion

Vericiguat reduces the risk of cardiovascular mortality or HF hospitalizations by an absolute event-rate reduction of 4.2 events per 100 patient-years with a number needed to treat of 24 patients, on a background of guideline-directed medical therapy. Almost 90% of the patients with HFrEF were adherent to the 10 mg dose of vericiguat in the VICTORIA trial with a favorable tolerability and safety profile. Considering the high residual risk that persists in HFrEF, vericiguat has a role to improve outcomes among patients with worsening HFrEF.

KEYWORDS:

• Heart failure
• heart failure with reduced ejection fraction
• HFrEF
• cardiovascular death
• hospitalization
• vericiguat
• soluble guanylate cyclase stimulator

Article highlights

• Despite significant therapeutic advancements in heart failure with reduced ejection fraction (HFrEF), the residual risk of all-cause mortality and hospitalizations remains high among patients with HFrEF.

• Vericiguat is a novel oral soluble guanylate cyclase (sGC) stimulator which was approved by the US Food and Drug administration (FDA) in January 2021 for use in patients with symptomatic chronic HF and an ejection fraction less than 45% following a hospitalization for HF or the need for outpatient intravenous diuretics.

• Vericiguat reduces the risk of cardiovascular mortality or HF hospitalizations by an absolute event-rate reduction of 4.2 events per 100 patient-years with a number needed to treat of 24 patients, on a background of guideline-directed medical therapy.

• Almost 90% of the patients with HFrEF were adherent to the 10 mg dose of vericiguat in the VICTORIA trial with a favorable tolerability and safety profile.

• Considering the high residual risk that persists in HFrEF, vericiguat has a role to improve outcomes among patients with worsening HFrEF.

• Vericiguat can be an excellent add-on fifth agent, owing to its unique mechanism of action of targeting guanylate cyclase, in patients with symptomatic, chronic HFrEF who have experienced a recent worsening event and are already on maximally tolerated GDMT, or in those patients who cannot tolerate GDMT and are at high risk of recurrent hospitalizations.

Declaration of Interest

SJ 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, Novartis, Pfizer, and Sanofi; has served on advisory boards for Amgen, AstraZeneca, Boehringer Ingelheim/ Lilly, Bristol Myers Squibb, Cytokinetics, Roche Diagnostics, Sanofi, and scPharmaceuticals; serves as a consultant for Amgen, Bayer, Bristol Myers Squibb, Boehringer Ingelheim/ Lilly, CSL Vifor, Merck, PharmaIN, Roche Diagnostics, Sanofi, Tricog Health, and Urovant Pharmaceuticals; and has received speaker fees from Boehringer Ingelheim and Cytokinetics. M Fudim is supported by the Mario Family Award, Duke Chair’s Award, Translating Duke Health Award, Bayer, and BTG Specialty Pharmaceuticals. He receives consulting fees from AxonTherapies, Bodyport, CVRx, Daxor, Edwards LifeSciences, Fire1, NXT Biomedical, Zoll, and Viscardia. RJ Mentz has received research support and honoraria from Abbott, American Regent, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim/Eli Lilly, Boston Scientific, Cytokinetics, Fast BioMedical, Gilead, Innolife, Medtronic, Merck, Novartis, Relypsa, Respicardia, Roche, Sanofi, Vifor, Windtree Therapeutics, and Zoll. J Butler is a consultant to Abbott, Adrenomed, Amgen, Applied Therapeutics, Array, AstraZeneca, Bayer, Boehringer Ingelheim, Cardior, CVRx, G3 Pharma, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, NovoNordisk, Relypsa, Roche, Sanofi, Sequana Medical, and Vifor.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.