Vericiguat for the treatment of heart failure: mechanism of action and pharmacological properties compared with other emerging therapeutic options

Expert Opin Pharmacother. 2021 Oct;22(14):1847-1855. doi: 10.1080/14656566.2021.1937121. Epub 2021 Jun 9.

Abstract

Introduction: The significant morbidity and mortality in patients with heart failure (HF), notably in the most advanced forms of the disease, justify the need for novel therapeutic options. In the last year, the soluble guanylate cyclase (sGC) stimulator, vericiguat, has drawn the attention of the medical community following the report of reduced clinical outcomes in patients with worsening chronic HF (WCHF).

Areas covered: The authors review the available data on the mechanism of action of vericiguat (cyclic guanosine monophosphate (cGMP) pathway), its clinical development program, its role in HF management, and its future positioning in the therapeutic recommendations.

Expert opinion: cGMP deficiency has deleterious effects on the heart and contributes to the progression of HF. Different molecules, including nitric oxide (NO) donors, phosphodiesterase inhibitors, and natriuretic peptides analogues, target the NO-sCG-cGMP pathway but have yielded conflicting results in HF patients. Vericiguat acts as a sGC stimulator thus targeting the NO-sGC-cGMP pathway by a different mechanism that complements the current pharmacotherapy for HF. Vericiguat has shown an additional statistical add-on therapy efficacy by reducing morbi-mortality in patients with WCHF. A better evaluation of HF severity might be an important determinant to guide the use of vericiguat among the available therapies.

Keywords: (5–8): cGMP pathway; heart failure (hf); heart failure hospitalization (hfh); heart failure with reduced ejection fraction (hfref); reduced left ventricular ejection fraction (lvef); sGC stimulator; soluble guanylate cyclase (sGC); ventricular remodeling; vericiguat; worsening chronic heart failure (wchf).

MeSH terms

  • Heart Failure* / drug therapy
  • Heterocyclic Compounds, 2-Ring*
  • Humans
  • Pyrimidines / pharmacology
  • Pyrimidines / therapeutic use
  • Soluble Guanylyl Cyclase
  • Stroke Volume

Substances

  • Heterocyclic Compounds, 2-Ring
  • Pyrimidines
  • Soluble Guanylyl Cyclase
  • vericiguat