A Systematic Review of the Effect of Vericiguat on Patients with Heart Failure
Abstract
:1. Introduction
1.1. Chronic Heart Failure
1.2. Standard of Care in CHF
1.3. Mechanism of Action of Vericiguat
2. Methods
3. Results and Discussion
3.1. The Phase II Trials
3.2. The Phase III Trial
3.3. Ongoing Trials on Vericiguat
3.4. Treatment Strategies and Risk Profiles
3.5. Effect on HFpEF
3.6. Safety of Vericiguat
3.7. NT-proBNP and BNP Levels in HF Patients
3.8. Vericiguat vs. Standard Pharmacological Treatment
3.9. The Effect on Physiological Parameters Compared to Quality of Life
3.10. Limitations and Future Perspectives
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Class of Drugs | Mechanism of Action | Drug Names |
---|---|---|
Angiotensin-converting enzyme inhibitors (ACEi) | The renin–angiotensin–aldosterone system (RAAS) plays a crucial role in maintaining the body’s fluid homeostasis and controlling blood pressure. ACEi block the conversion of angiotensin I to angiotensin II, which in turn prevents the release of aldosterone from the adrenal glands, promoting a decrease in blood pressure [19,20,21]. | Lisinopril, Enalapril, Ramipril Perindopril Trandolapril |
Angiotensin receptor blockers (ARBs) | ARBs block the AT1 receptors and are often used as an alternative drug in cases where ACEi are not tolerated [5]. | Losartan, Valsartan Candesartan |
Beta-adrenoceptor antagonists (BAAs) | BAAs bind to beta-adrenoceptors and block the binding of catecholamines (norepinephrine, epinephrine) to these receptors. The inhibition of the binding of catecholamines results in a reduction in HR and also a lowering in SBP [22]. | Carvedilol, Bisoprolol, Metoprolol succinate |
Mineralocorticoid receptor antagonists (MRAs) | MRAs inhibit aldosterone’s epithelial and nonepithelial actions, thus exerting its function in the heart, kidney, and vascular beds. MRAs have the same outcome as both ACEi and ARBs [23]. | Spironolactone, Eplerenone |
Diuretics | Diuretics promote diuresis by inhibiting the function of Na–K–Cl cotransporters (NKCC) in the thick ascending tubule of the nephron. They inhibit sodium reabsorption, thus preventing water reabsorption, and the water is excreted in the urine [24]. However, they also increase vasodilatory prostaglandins and the pressure within the proximal tubule [25]. | Furosemide, Bumetanide, Thiazides |
Sodium–glucose transport protein 2 (SGLT2) inhibitor | SGLT-2 inhibitors increase glucose excretion in the kidneys through selective, reversible inhibition of glucose reabsorption in the proximal renal tubules, thus leading to less water reabsorption. This lowers the blood volume in the body, thus lowering the blood pressure [26]. | Dapagliflozin, Canagliflozin, Empagliflozin |
Combination drug (ARNi) sacubitril/valsartan | The angiotensin receptor II blocker valsartan and the neprilysin inhibitor sacubitril are used in patients with reduced ejection fraction to reduce the risk of hospitalization and improve survival [27]. | Entresto |
Ivabradine | Used for the symptomatic management of heart-related long-term stable angina in patients with coronary artery disease. It has shown effectiveness and is only recommended to patients with an HR > 70. Ivabradine is used in addition to other guideline-directed therapy. The drug works by blocking the ion current in the funny channels (also known as current) in the sinoatrial (SA) node. The SA node is the pacemaker of the heart [24], and when treated with ivabradine, the heart rate is lowered. The heart works less and requires less blood that has been oxygenated. Therefore, procoralan lessens or stops the symptoms of angina [28]. | Procoralan |
Digoxin | Treatment with digoxin inhibits the sodium–potassium ATPase pump, resulting in positive cardiac inotropy in addition to a reduced effect from the sympathetic nervous system and responses from RAAS. The drug is used in cases of atrial fibrillation, atrial flutter, and HF [29]. | Lanoxin |
Study Title (Clinicaltrials.gov Identifier) | Eligibility | Participants | Dose Regimen | Endpoints | Phase | Status |
---|---|---|---|---|---|---|
A study to learn how well the drug vericiguat works and how safe it is under real-world conditions in Indian participants after the worsening of a long-term heart condition in which the left side of the heart does not pump blood as well as it should. (Chronic Heart Failure with Reduced Ejection Fraction) (NCT05658458) | Age ≥ 18 years LVEF < 45%, NYHA class II–IV symptoms | 200 | Starting dose 2.5 mg daily, dose doubled every two weeks, end dose 10 mg daily. | CV death and HF hospitalization | 4 | Recruiting |
The anti-myocardial fibrosis effect of vericiguat in HFrEF (ANF-HF) (NCT05799638) | Age ≥ 18 years Diagnosed with HFrEF LVEF < 45% NYHA classes II–IV | 60 | Started at 2.5 mg once daily and up-titrated to 5 mg at week 3 and to 10 mg at week 5 | The primary endpoint is the change in extracellular volume (ECV) measured by CMR. | 4 | Recruiting |
Study of vericiguat (MK-1242) in participants with chronic heart failure with reduced ejection fraction (HFrEF) (MK-1242-035) (VICTOR) (NCT05093933) | (NYHA) Class II–IV LVEF of ≤40% Elevated NT-proBNP levels | 6000 | 2.5, 5.0, or 10.0 mg orally once daily | Composite endpoint of CV death or HF hospitalization | 3 | Recruiting |
A study to learn more about the safety of the drug vericiguat in Japanese people with chronic heart failure who will be receiving vericiguat under real-world conditions. (NCT05666518) | Child, Adult, Older Adult NT-proBNP ≥ 1000 pg/mL or Brain Natriuretic Peptide (BNP) ≥ 192 pg/mL (sinus rhythm), NT-proBNP ≥ 1600 pg/mL or BNP ≥ 319 pg/mL (atrial fibrillation) NYHA) Class II to IV LVEF of ≤40% | 1400 | Dosage at the discretion of the treating physician | Incidence of CV death for vericiguat arm and control arm | Observational study | Recruiting |
Efficacy, safety, and pharmacokinetics of vericiguat in pediatric participants with heart failure due to left ventricular systolic dysfunction (MK-1242-036) (NCT05714085) | Children: 29 days to 17 years; history of symptomatic chronic HF resulting from systemic left ventricular (LV) systolic dysfunction LVEF) < 45% assessed within 3 months | 342 | 2.5 mg or 5 mg or 10 mg tablet daily. 0.2 mg/mL or 1 mg/mL in suspension form. | Change from baseline to week 16 in N-terminal pro-brain natriuretic peptide (NT-proBNP) and log-transformed NT-proBNP. | 2/3 | Recruiting |
The effect of vericiguat on peripheral vascular function, patient health status, and inflammation (NCT05420012) | Age ≥ 18 years, NYHA) Class II to III; LVEF < 45% History of chronic symptomatic HF (ACC/AHA Class C) and New York Heart Association (NYHA) Class II or III symptoms at the time of enrollment. | 24 | Starting dose of vericiguat 2.5 mg, up-titrated to 5 mg and 10 mg in a blinded fashion. | Changes in vascular function using flow-mediated vasodilation (FMD) and the six-minute walk test (6 MWT). | 4 | Recruiting |
An observational study, called VERI-China, to learn more about how well vericiguat works and how safe it is in a real-world setting in people with chronic heart failure with reduced ejection fraction (HFrEF) in China (VERI-China) (NCT05728502) | Age ≥ 18 years, Patients with HFrEF after a recent decompensation episode (within 6 months of HF hospitalization or within 3 months of intravenous (IV) diuretics for HF not requiring hospitalization) | 2400 | Dosage at the discretion of the treating physician | Time to first occurrence of the composite of cardiovascular (CV) death or first hospitalization due to Heart Failure (HF) | Observational study | Recruiting |
Impact of vericiguat on the hemodynamics of heart failure (NCT05704478) | Adults 18 years of age or older with NYHA functional class II, III, or IV HFrEF with LVEF < 45% within 12 months of enrollment. Elevated BNP within 30 days of enrollment; History of HF- hospitalization within 6 months of enrollment or increase in diuretic therapy without hospitalization within 3 months of enrollment | 30 | Soluble guanylate cyclase stimulator, dose not mentioned | Cardiac output (L/min) from heart catheterization. Quality-of-life assessment. | 4 | Not Yet Recruiting |
Trial | AEs | SAE | Treatment-Emergent AEs | ||||||
---|---|---|---|---|---|---|---|---|---|
Hypotension | Syncope | Anemia | Renal Disorder | GIT Disorder | Dizziness | Headache | |||
SOCRATES-PRESERVED (NCT01951638) | 69.8% | 25% | 4.4% | 0.0% | NA | 5.9% | NA | NA | NA |
SOCRATES-REDUCED (NCT01951625) | 71.4% | 31.9% | 15.4% | 4.4% | NA | Acute kidney injury 3.3% | NA | NA | NA |
VITALITY (NCT03547583) | 62.2% | 17.6% | 4.2% | 0.8% | NA | NA | NA | NA | NA |
VICTORIA (NCT02861534) | 80.5% | 32.8% | 9.1% | 4.0% | 1.6% | 17% | 25.3% | 18.5% | 3.4% |
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Sahana, U.; Wehland, M.; Simonsen, U.; Schulz, H.; Grimm, D. A Systematic Review of the Effect of Vericiguat on Patients with Heart Failure. Int. J. Mol. Sci. 2023, 24, 11826. https://doi.org/10.3390/ijms241411826
Sahana U, Wehland M, Simonsen U, Schulz H, Grimm D. A Systematic Review of the Effect of Vericiguat on Patients with Heart Failure. International Journal of Molecular Sciences. 2023; 24(14):11826. https://doi.org/10.3390/ijms241411826
Chicago/Turabian StyleSahana, Urjosee, Markus Wehland, Ulf Simonsen, Herbert Schulz, and Daniela Grimm. 2023. "A Systematic Review of the Effect of Vericiguat on Patients with Heart Failure" International Journal of Molecular Sciences 24, no. 14: 11826. https://doi.org/10.3390/ijms241411826