Victoria and Victor: event-driven lessons for integrating vericiguat into practice and reducing residual risk in HFrEF

Abstract

Chronic heart failure with reduced ejection fraction (HFrEF) is a progressive syndrome associated with substantial residual morbidity and mortality despite contemporary guideline-directed medical therapy (GDMT) - angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs)/angiotensin receptor-neprilysin inhibitors (ARNIs), beta-blockers, mineralocorticoid receptor antagonists (MRAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) [1]. Consequently, the need for novel therapeutic strategies has led to the exploration of new drug classes and pathways. In HF, impaired nitric-oxide (NO) signaling, reduced soluble guanylate cyclase (sGC) responsiveness/abundance, and downstream attenuation of cyclic guanosine monophosphate (cGMP) contribute to disease progression [2]. Vericiguat-an oral sGC stimulator-sensitizes sGC to endogenous NO and directly stimulates the enzyme, thereby restoring cGMP signaling in vascular smooth muscle and cardiomyocytes.