Vericiguat for Heart Failure with Reduced Ejection Fraction

Purpose of Review The nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) pathway plays an important role in the regulation of cardiovascular function, and it is disrupted in heart failure (HF), resulting in decreased protection against myocardial injury. Impaired NO-sGC-cGMP signaling in HF is secondary to reduced NO bioavailability and altered redox state of sGC, which becomes less responsive to NO. The sGC activator cinaciguat increases cGMP levels by direct NO-independent activation of sGC and may be particularly effective in conditions of increased oxidative stress and endothelial dysfunction, and therefore reduced NO levels, at the expense of a greater risk of hypotension. Conversely, sGC stimulators (riociguat and vericiguat) enhance sGC sensitivity to endogenous NO, thus exerting a more physiological action. Recent Findings Clinical trials have suggested the benefit of vericiguat in patients with high-risk HF; in particular, a lower incidence of death from cardiovascular causes or HF hospitalization. Adding vericiguat may be considered in individual patients with HF, and reduced left ventricular ejection fraction (HFrEF) particularly those at higher risk of HF hospitalization.