Vericiguat: A Novel Soluble Guanylate Cyclase Stimulator for Use in Patients With Heart Failure

Abstract

Heart failure (HF) affects 6.2 million Americans and is increasing annually in its frequency. Treatment of HF has been at the forefront of medical advancements due to the financial burden on our health care system. As such, changes to the guidelines regarding standard of care have been evolving over the last decade with the recent additions of sacubitril-valsartan and sodium glucose co-transporter-2 inhibitors to standard of care in the treatment of HF. Despite the aforementioned expansions in treatment options, HF continues to have a significant impact on the American health care system. Most recently, a novel drug vericiguat that targets an unprecedented pathway for the treatment of HF was Food and Drug Administration approved for the management of patients with HF with a reduced ejection fraction with a recent hospitalization or need for outpatient intravenous diuretics. In clinical trials, vericiguat was associated with a reduction in death from cardiovascular causes and first hospitalization in comparison to placebo. The aim of this review is to provide a comprehensive literature analysis of the various trials surrounding the approval of vericiguat and to both inform and synthesize the data surrounding the clinical use of vericiguat. The introduction of Vericiguat should be considered as a treatment option in patients to decrease the mortality/morbidity of HF with reduced ejection fraction and to increase the quality of life.

Efficacy and safety of vericiguat in heart failure: a meta-analysis

“…In addition, some studies also recommended taking vericiguat in HF. 25,26 Finally, due to the study design, studies reporting the effects of combinations of drugs in patients with HF were not included in the present meta-analysis. Notably however, recent studies of the combination of vericiguat with isosorbide mononitrate (VISOR study) and nitroglycerin (VENICE study) showed that vericiguat slightly lowered blood pressure, similar to the placebo group, indicating minimal adverse effects of vericiguat in HF.…”

New Therapeutics for Heart Failure: Focusing on cGMP Signaling

“…It stimulates sGC directly in a NO-independent manner [ 62 ]. Vericiguat, which has similar activity, but a longer duration of action compared with riociguat, improved HF symptoms in patients and reduced death due to CV defects, with additive effects in patients receiving standard treatment for chronic HF [ 63 ].…”

“…The progression of chronic HF is inhibited when blood vessels dilate and BP is reduced. However, sGC stimulants are also effective at correcting reductions in BP, indicating that their direct action on the heart is also protective against HF [ 62 , 63 , 64 ]. In other words, a decrease in NO production by endothelial cells results in a decrease in tissue cGMP levels.…”

“…cGMP is a signaling molecule that regulates physiological processes such as myocardial contraction, vascular tone, and cardiac remodeling [ 2 , 3 ]. Therefore, a decrease in cGMP levels creates negative feedback between myocardial and vascular dysfunction, which in turn leads to further worsening of HF [ 62 , 63 , 64 ]. β-Blockers and other drugs that have become the standard of care for HF are not thought to act on the NO–sGC–cGMP signaling pathway.…”

“…sGC-mediated cGMP signaling plays a crucial role in regulating normal cardiovascular and cardiopulmonary functions [ 62 ]. Activation of sGC by its endogenous ligand, nitric oxide (NO), leads to the production of cGMP, which in turn stimulates various downstream signaling pathways involved in regulating vascular tone, including vasodilation and several cellular functions [ 62 , 63 ]. However, the endothelial dysfunction commonly observed in HF can result in impaired NO production, leading to reduced cGMP production and progression of HF and CVDs [ 64 ].…”