Vericiguat: A New Hope for Heart Failure Patients

Chiles, Raquel; Al‐Horani, Rami A.

doi:10.1155/2022/1554875

Cited by 8 publications

(13 citation statements)

References 18 publications

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“…Elevated levels of cGMP have been associated with improved cardiac contractility [39], as the heart muscle can contract more forcefully and pump blood more effectively. Thus, vericiguat reduces cardiac hypertrophy, which is the thickening of the heart muscle due to chronic pressure overload [40]. By reducing hypertrophy, vericiguat may help to prevent or reverse the pathologic structural remodeling of the heart, leading to improved heart function.…”

Section: Mechanism Of Action Of Vericiguatmentioning

confidence: 99%

A Systematic Review of the Effect of Vericiguat on Patients with Heart Failure

Sahana,

Wehland,

Simonsen

et al. 2023

IJMS

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Despite recent advances in heart failure (HF) therapy, the risk of cardiovascular (CV) mortality, morbidity, and HF hospitalization (HFH) are major challenges in HF treatment. We aimed to review the potential of vericiguat as a treatment option for HF. A systematic literature review was performed using the PubMed database and ClinicalTrials.gov. Four randomized controlled trials were identified, which study the safety and efficacy of vericiguat in HF patients. Vericiguat activates soluble guanylate cyclase (sGC) by binding to the beta-subunit, bypassing the requirement for NO-induced activation. The nitric oxide (NO)–sGC–cyclic guanosine monophosphate (cGMP) pathway plays an essential role in cardiovascular (CV) regulation and the protection of healthy cardiac function but is impaired in HF. Vericiguat reduced the risk of CV death and HFH in HF patients with reduced ejection fraction (HFrEF) but showed no therapeutic effect on HF with preserved ejection fraction (HFpEF). The trials demonstrated a favorable safety profile with most common adverse events such as hypotension, syncope, and anemia. Therefore, vericiguat is recommended for patients with HFrEF and a minimum systolic blood pressure of 100 mmHg. Treatment with vericiguat is considered when the individual patient experiences decompensation despite being on guideline-recommended medication, e.g., angiotensin-converting inhibitor/AT1 receptor antagonist, beta-adrenoceptor antagonist, spironolactone, and sodium-glucose transporter 2 inhibitors. Furthermore, larger studies are required to investigate any potential effect of vericiguat in HFpEF patients. Despite the limitations, vericiguat can be recommended for patients with HFrEF, where standard-of-care is insufficient, and the disease worsens.

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Section: Mechanism Of Action Of Vericiguatmentioning

confidence: 99%

A Systematic Review of the Effect of Vericiguat on Patients with Heart Failure

Sahana,

Wehland,

Simonsen

et al. 2023

IJMS

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“…A growing body of preclinical and clinical evidence revealed that the stimulation of the nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate (NO-sGC-cGMP) pathway by sGC stimulators represents a potential therapeutic approach for the management of HF [ 9 ]. The sGC enzyme is an intracellular nitric oxide (NO) receptor that catalyzes the synthesis of the second messenger cyclic guanosine monophosphate (cGMP), when activated [ 10 ].…”

Section: An Overview Of Vericiguatmentioning

confidence: 99%

Towards the Fifth Pillar for the Treatment of Heart Failure with Reduced Ejection Fraction: Vericiguat in Older and Complex Patients

Spadafora,

Bernardi,

Sarto

et al. 2024

Am J Cardiovasc Drugs

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Heart failure with reduced ejection fraction (HFrEF) represents an emerging epidemic, particularly affecting frail, older, and multimorbid patients. Current therapy for the management of HFrEF includes four different classes of disease-modifying drugs, commonly referred to as ‘four pillars’, which target the neurohormonal system that is overactivated in HF and contributes to its progression. These classes of drugs include β-blockers, inhibitors of the renin-angiotensin-aldosterone system, mineralocorticoid receptor antagonists, and sodium-glucose co-transporter-2 (SGLT2) inhibitors. Unfortunately, these agents cannot be administered as frequently as needed to older patients because of poor tolerability and comorbidities. In addition, although these drugs have dramatically increased the survival expectations of patients with HF, their residual risk of rehospitalization and death at 5 years remains considerable. Vericiguat, a soluble guanylate cyclase (sGC) stimulator, was reported to exert beneficial effects in patients with worsening HF, including older subjects, reducing the rate of both hospitalizations and deaths, with limited adverse effects and drug interaction. In this narrative review, we present the current state of art on vericiguat, with a particular focus on elderly and frail patients.

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“…The median follow-up for the primary endpoint was 11 months. The annualized absolute risk reduction with the drug treatment was ~4.2% over the course of the study [148]. The recommended initial oral dose of vericiguat was 2.5 mg/day, with food intake, and should be doubled approximately every 2 weeks to reach the target maintenance dose of 10 mg/day.…”

Section: Drug Targeting Of Mitochondrial Ca 2+ and Homeostasismentioning

confidence: 99%

Calcium and Reactive Oxygen Species Signaling Interplays in Cardiac Physiology and Pathologies

et al. 2023

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Mitochondria are key players in energy production, critical activity for the smooth functioning of energy-demanding organs such as the muscles, brain, and heart. Therefore, dysregulation or alterations in mitochondrial bioenergetics primarily perturb these organs. Within the cell, mitochondria are the major site of reactive oxygen species (ROS) production through the activity of different enzymes since it is one of the organelles with the major availability of oxygen. ROS can act as signaling molecules in a number of different pathways by modulating calcium (Ca2+) signaling. Interactions among ROS and calcium signaling can be considered bidirectional, with ROS regulating cellular Ca2+ signaling, whereas Ca2+ signaling is essential for ROS production. In particular, we will discuss how alterations in the crosstalk between ROS and Ca2+ can lead to mitochondrial bioenergetics dysfunctions and the consequent damage to tissues at high energy demand, such as the heart. Changes in Ca2+ can induce mitochondrial alterations associated with reduced ATP production and increased production of ROS. These changes in Ca2+ levels and ROS generation completely paralyze cardiac contractility. Thus, ROS can hinder the excitation–contraction coupling, inducing arrhythmias, hypertrophy, apoptosis, or necrosis of cardiac cells. These interplays in the cardiovascular system are the focus of this review.

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Vericiguat: A New Hope for Heart Failure Patients

Cited by 8 publications

References 18 publications

A Systematic Review of the Effect of Vericiguat on Patients with Heart Failure

A Systematic Review of the Effect of Vericiguat on Patients with Heart Failure

Towards the Fifth Pillar for the Treatment of Heart Failure with Reduced Ejection Fraction: Vericiguat in Older and Complex Patients

Calcium and Reactive Oxygen Species Signaling Interplays in Cardiac Physiology and Pathologies

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