Vericiguat in Heart Failure: Characteristics, Scientific Evidence and Potential Clinical Applications

Despite recent advances in heart failure (HF) management, the risk of death and hospitalizations remains high in the long term. HF is characterized by endothelial dysfunction, inflammation and increased oxidative stress, due to a reduction in the activity of the nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) signaling pathway. All these factors contribute to direct damage at the myocardial, vascular and renal level. Vericiguat 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. Two main clinical trials were developed in this setting: the SOCRATES-REDUCED phase II study and the VICTORIA phase III study. They found that vericiguat is safe, well tolerated and effective with an absolute event-rate reduction in patients affected by HF with reduced ejection fraction (HFrEF) and recent cardiac decompensation. In patients with HF with preserved ejection fraction (HfpEF), the SOCRATES-PRESERVED trial demonstrated an improvement in quality of life and health status, but the proven beneficial effects with vericiguat are still limited. Further studies are needed to correctly define the role of this drug in heart failure syndromes. Our paper reviews the potential applications and pharmacological characteristics of vericiguat in HFrEF and HFpEF.