The sGC stimulator vericiguat provides cardiovascular benefits and may be considered in addition to standard therapy for adults with symptomatic HFrEF following a worsening event.
This review summarizes the molecular mechanisms, preclinical evidence, and clinical trial data supporting the use of sGC stimulators like vericiguat in heart failure management.
Despite recent advances in pharmacological treatment, chronic heart failure (HF) is associated with significant morbidity and mortality, and further treatment options are needed. Intact nitric oxide (NO)-soluble guanylyl cyclase (sGC)-cyclic guanosine monophosphate (cGMP) signalling is a prerequisite of cardiovascular health. cGMP produced by NO/NO-sGC acts as a second messenger molecule via various downstream targets, which influence a broad spectrum of critical physiological parameters. Impairment of this cascade in the cardiovascular system is considered an important pathomechanism in HF. This review examines pharmacological therapies that act through the NO-sGC-cGMP signalling pathway. We will focus on the molecular mode(s) of action of NO-independent but haem-dependent sGC stimulators, and will examine evidence from preclinical studies demonstrating cardiovascular benefits of these therapies and their increasing number of effects on other susceptible tissues and organs, which together could contribute to clinical outcomes in HF. The sGC stimulator vericiguat may be considered, in addition to standard therapy, for adults with symptomatic HF with reduced ejection fraction (HFrEF) following a worsening event. The findings from pivotal clinical trials that led to these recommendations will be outlined and classified in terms of their significance for different subpopulations. These include the phase 3 VICTORIA and VICTOR trials. Finally, further research areas and ongoing studies designed to address existing gaps in our knowledge regarding vericiguat and related drugs will be highlighted.
Ruschitzka et al. (Fri,) conducted a review in Heart failure with reduced ejection fraction (HFrEF). sGC stimulators (vericiguat) vs. Standard therapy was evaluated. The sGC stimulator vericiguat provides cardiovascular benefits and may be considered in addition to standard therapy for adults with symptomatic HFrEF following a worsening event.