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Review
. 2024 Jul;24(4):469-479.
doi: 10.1007/s40256-024-00652-6. Epub 2024 Jun 10.

Towards the Fifth Pillar for the Treatment of Heart Failure with Reduced Ejection Fraction: Vericiguat in Older and Complex Patients

Luigi Spadafora  1 , Marco Bernardi  2 , Gianmarco Sarto  3 , Beatrice Simeone  3 , Maurizio Forte  4 , Luca D'Ambrosio  5 , Matteo Betti  6 , Alessandra D'Amico  5 , Vittoria Cammisotto  2 , Roberto Carnevale  4   5 , Simona Bartimoccia  5 , Pierre Sabouret  7   8 , Giuseppe Biondi Zoccai  5   9 , Giacomo Frati  4   5 , Valentina Valenti  5 , Sebastiano Sciarretta  4   5 , Erica Rocco  3
Affiliations
Review

Towards the Fifth Pillar for the Treatment of Heart Failure with Reduced Ejection Fraction: Vericiguat in Older and Complex Patients

Luigi Spadafora et al. Am J Cardiovasc Drugs. 2024 Jul.

Abstract

Heart failure with reduced ejection fraction (HFrEF) represents an emerging epidemic, particularly affecting frail, older, and multimorbid patients. Current therapy for the management of HFrEF includes four different classes of disease-modifying drugs, commonly referred to as 'four pillars', which target the neurohormonal system that is overactivated in HF and contributes to its progression. These classes of drugs include β-blockers, inhibitors of the renin-angiotensin-aldosterone system, mineralocorticoid receptor antagonists, and sodium-glucose co-transporter-2 (SGLT2) inhibitors. Unfortunately, these agents cannot be administered as frequently as needed to older patients because of poor tolerability and comorbidities. In addition, although these drugs have dramatically increased the survival expectations of patients with HF, their residual risk of rehospitalization and death at 5 years remains considerable. Vericiguat, a soluble guanylate cyclase (sGC) stimulator, was reported to exert beneficial effects in patients with worsening HF, including older subjects, reducing the rate of both hospitalizations and deaths, with limited adverse effects and drug interaction. In this narrative review, we present the current state of art on vericiguat, with a particular focus on elderly and frail patients.

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Conflict of interest statement

Luigi Spadafora, Marco Bernardi, Gianmarco Sarto, Beatrice Simeone, Maurizio Forte, Luca D’Ambrosio, Matteo Betti, Alessandra D’Amico, Vittoria Cammisotto, Roberto Carnevale, Simona Bartimoccia, Giuseppe Biondi Zoccai, Giacomo Frati, Sebastiano Sciarretta, Valentina Valenti and Erica Rocco declare they have no potential conflicts of interest that might be relevant to the contents of this manuscript. Pierre Sabouret reports consulting fees from Axis-TV, Astra-Zeneca, BMS, Les Laboratoires Servier, Novartis, Menarini and Sanofi, outside the submitted work.

Figures

Fig. 1
Fig. 1
Impact of vericiguat in modulating the NO-sGC-cGMP pathway. NO-sGC-cGMP nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate, GTP guanosine triphosphate
Fig. 2
Fig. 2
Features of vericiguat in older and complex patients, HFrEF heart failure with reduced ejection fraction, OMT optimal medical therapy
Fig. 3
Fig. 3
Proposed algorithm for the use of vericiguat in older and complex patients. ARNI angiotensin receptor/neprilysin inhibitor, BB β-blockers, HF heart failure, HFrEF heart failure with reduced ejection fraction, MRA mineralocorticoid receptor antagonist, OMT optimal medical therapy, PDE-5 phosphodiesterase-5, RASi renin-angiotensin-aldosterone system inhibitors, SBP systolic blood pressure, SGLT2i sodium-glucose co-transporter-2 inhibitors, UTI urinary tract infection, WRF worsening renal function
See this image and copyright information in PMC

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