Use of soluble guanylyl cyclase stimulators in heart failure therapy-a mode of action perspective
Abstract
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 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…
Read the paper
Related studies
- Drug repositioning: a brief overview
- Cyclic nucleotide phosphodiesterases in Drosophila melanogaster
- Time-resolved in silico modeling of fine-tuned cAMP signaling in platelets: feedback loops, titrated phosphorylations and pharmacological modulation
- Current View on Green Tea Catechins Formulations, Their Interactions with Selected Drugs, and Prospective Applications for Various Health Conditions
- In silico Structure-based Identification of Novel Acetylcholinesterase Inhibitors Against Alzheimer’s Disease
- Development and In Vitro Evaluation of Controlled Release Viagra® Containing Poloxamer-188 Using Gastroplus™ PBPK Modeling Software for In Vivo Predictions and Pharmacokinetic Assessments
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.