European Journal of Cardiovascular Medicine

Background:  Despite recent advances in heart failure (HF) management, mortality and morbidity remain high in patients with heart failure with reduced and preserved ejection fraction. HF is characterized by endothelial dysfunction, inflammation, and increased oxidative stress that results due to a reduction in the activity of the nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate (NO-sGC-cGMP) signaling pathway. All these factors contribute to direct damage at the myocardial, vascular, and renal levels. At a fundamental level, it is known that this cardioprotective pathway of NO-sGC-cGMP is impaired in heart failure patients. Materials and Methods: Vericiguat is a soluble guanylate cyclase stimulator approved by various global regulatory bodies in January 2021 and recommended in recently updated clinical practice guidelines to reduce morbidity and mortality in patients with worsening chronic heart failure (HF) with reduced ejection fraction (HFrEF). It is a novel, orally used, small molecule, and direct stimulator of the soluble guanylate cyclase. It restores the deficiency in this signaling pathway, through stimulation and activation of sGC, aiming to increase cGMP levels, with a reduction in HF-related oxidative stress and endothelial dysfunction. For the present systematic review a Boolean search was carried out in Pubmed, Google Scholar and Embase. Conclusion: Overall, four main clinical trials have been carried out for vericiguat namely the SOCRATES-REDUCED, SOCRATES - PRESERVED, VICTORIA, and VITALITY. Vericiguat resulted in reduced CV death and HF hospitalization in patients with HFrEF and a recent episode of cardiac decompensation.