Comprehensive Guide to Vericiguat in Heart Failure Treatment

What is Vericiguat and its role in Heart Failure with Reduced Ejection Fraction?

Vericiguat is a novel medication that has shown promising results in the management of heart failure with reduced ejection fraction (HFrEF). It belongs to the class of drugs known as soluble guanylate cyclase (sGC) stimulators.

Vericiguat works by increasing the activity of sGC, leading to the production of cyclic guanosine monophosphate (cGMP). This, in turn, relaxes blood vessels, reduces inflammation, and improves cardiac function.

In the VICTORIA trial, vericiguat demonstrated a significant reduction in heart failure hospitalizations and cardiovascular death in patients with HFrEF when added to standard therapy. The trial involved over 5,000 patients with symptomatic HF and reduced ejection fraction who were already receiving guideline-directed medical therapy.

Vericiguat has the potential to be a valuable addition to the treatment armamentarium for patients with HFrEF, providing another option to further reduce the burden of symptoms and improve outcomes in this population. However, further studies are needed to elucidate its long-term effects and safety profile.

What is Chronic Heart Failure and how it is related to Vericiguat

Chronic Heart Failure (CHF) is a progressive, long-term condition where the heart muscle is unable to pump enough blood to meet the body’s needs for blood and oxygen.

CHF usually result from conditions that overwork the heart such as high blood pressure, coronary artery disease, or past heart attacks. The role of Vericiguat in the treatment of CHF has become increasingly significant.

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Vericiguat is an oral soluble guanylate cyclase (sGC) stimulator used in the management of heart failure. Its use primarily targets patients with a reduced ejection fraction who are at a higher risk of hospitalization or cardiovascular death. Vericiguat functions by enhancing the sensitivity of sGC to endogenous nitric oxide, a fundamental mechanism in the cardiovascular system.

This helps maintain vasodilatory tone, reduces preload and afterload on the failing heart, and improves cardiac output. Thus, including Vericiguat as a part of a holistic treatment plan for CHF can contribute to better overall patient outcomes. 

Clinical Trial: The VICTORIA Trial

This study was a phase 3 trial that investigated the effects of vericiguat on patients with chronic heart failure. The patients were randomly assigned to receive either vericiguat or a placebo in addition to their usual medical therapy. The primary outcome measured was a composite of death from cardiovascular causes or the first hospitalization for heart failure.

Key points of the VICTORIA trial:

• The study was a phase 3 trial involving 5050 patients with chronic heart failure.
• Patients were randomly assigned to receive either vericiguat or a placebo.
• The primary outcome measured was a combination of death from cardiovascular causes or the first hospitalization for heart failure.

Mechanism of Action of Vericiguat

How does Vericiguat work?

The MOA is stepwise as follows

1. Vericiguat enhances production of cyclic guanosine monophosphate.
2. This is achieved by directly stimulating soluble guanylate cyclase independent of nitric oxide.
3. Vericiguat also enhances soluble guanylate cyclase sensitivity to endogenous nitric oxide.
4. This increases the production of cyclic guanosine monophosphate.
5. Increased levels of cyclic guanosine monophosphate lead to smooth muscle relaxation and vasodilation.

Vericiguat’s effects on the left ventricular ejection fraction

• Vericiguat showed a lower risk of primary outcome events and composite outcome of death or hospitalization compared to placebo.
• Hospitalization for heart failure was similar between vericiguat and placebo groups.
• Vericiguat did not significantly reduce death from cardiovascular causes.
• Rates of symptomatic hypotension and syncope were similar between the two groups.

Vericiguat as an add-on therapy for heart failure: Is it effective?

Yes it is. The study found that patients with high-risk heart failure who received vericiguat had a lower incidence of death from cardiovascular causes or hospitalization for heart failure compared to those who received a placebo.

Vericiguat 10 mg: Is this the optimal dose?

In patients with heart failure and reduced ejection fraction, additional therapy may be considered if they remain symptomatic despite optimal medical treatment. However, the use of long-acting nitrates or PDE-5 inhibitors should be avoided because they can cause low blood pressure.

• The initial dose of oral medication is 2.5 mg once daily with food.
• The dose should be doubled every 2 or more weeks until a target maintenance dose of 10 mg once daily is reached.
• Blood pressure should be monitored to guide dose adjustments.
• If systolic blood pressure is ≥100 mm Hg, consider increasing the dose to the target dose of 10 mg. If it is ≥90 and <100 mm Hg, maintain the current dose. If it is <90 mm Hg, decrease the dose or interrupt therapy depending on the current dose and presence of symptomatic hypotension.