What is Vericiguat used for?

Vericiguat is a novel pharmaceutical agent that has emerged as a valuable option in the treatment of chronic heart failure. It is marketed under the trade name Verquvo. This drug was developed through a collaboration between Bayer and Merck & Co. and has been approved by the U.S. Food and Drug Administration (FDA) for use in adults with symptomatic chronic heart failure with reduced ejection fraction (HFrEF). The primary target of Vericiguat is soluble guanylate cyclase (sGC), an enzyme that plays a crucial role in the nitric oxide (NO) signaling pathway, which is often impaired in patients with heart failure. By enhancing the activity of sGC, Vericiguat helps to improve cardiovascular function and symptoms in patients with heart failure.

Vericiguat was subjected to rigorous clinical trials to evaluate its efficacy and safety. The VICTORIA (Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction) trial was a pivotal phase III clinical study that enrolled over 5,000 patients with chronic heart failure who were at high risk of hospitalization. The results of this trial demonstrated that Vericiguat significantly reduced the risk of cardiovascular death or heart failure hospitalization compared to placebo, leading to its approval for clinical use.

Vericiguat Mechanism of Action

The mechanism of action of Vericiguat is centered on its ability to stimulate soluble guanylate cyclase (sGC), an enzyme that is an essential part of the nitric oxide (NO) signaling pathway. In patients with heart failure, the NO signaling pathway is often dysregulated due to oxidative stress and endothelial dysfunction. This results in reduced availability of NO, which in turn impairs sGC activity and leads to decreased production of cyclic guanosine monophosphate (cGMP). cGMP is a critical signaling molecule that helps relax blood vessels, reduce inflammation, and prevent heart muscle remodeling.

Vericiguat directly stimulates sGC, even in the presence of low NO levels, and increases the production of cGMP. This enhancement of cGMP levels leads to vasodilation, improved endothelial function, and reduced cardiac remodeling. Consequently, Vericiguat helps to alleviate symptoms of heart failure, improve exercise capacity, and reduce the risk of hospitalization for heart failure exacerbations.

How to Use Vericiguat

Vericiguat is administered orally in the form of tablets. The recommended starting dosage is 2.5 mg once daily, taken with food. To reduce the risk of side effects and enhance patient tolerance, the dose is typically increased gradually. After two weeks, the dosage is escalated to 5 mg once daily, and if well-tolerated, it is then further increased to the target maintenance dose of 10 mg once daily. It is crucial for patients to adhere to their prescribed dosage regimen and not to discontinue the medication without consulting their healthcare provider.

The onset time for Vericiguat’s therapeutic effects can vary among patients. However, clinical studies suggest that significant improvements in symptoms and reductions in hospitalization risk can be observed within a few weeks of initiating treatment. It is important to note that the full benefits of Vericiguat may take several months to manifest, and patients should continue taking the medication as prescribed by their healthcare provider.

What is Vericiguat Side Effects

Like any medication, Vericiguat can cause side effects, and patients should be aware of potential adverse reactions. The most common side effects of Vericiguat include hypotension (low blood pressure) and gastrointestinal symptoms such as nausea, diarrhea, and dyspepsia. These side effects are generally mild to moderate in severity and tend to diminish as the patient becomes accustomed to the medication.

More serious side effects are less common but can occur. These include symptomatic hypotension, which can lead to dizziness, lightheadedness, and fainting. Patients are advised to monitor their blood pressure regularly and report any significant drops or symptoms of hypotension to their healthcare provider. Additionally, Vericiguat can cause anemia, so regular blood tests may be required to monitor hemoglobin levels.

There are certain contraindications for the use of Vericiguat. It should not be used in patients who are concurrently taking other medications that increase cGMP levels, such as nitrates or phosphodiesterase-5 (PDE-5) inhibitors, due to the risk of severe hypotension. Furthermore, Vericiguat is contraindicated in pregnant women, as it may cause harm to the developing fetus. Women of childbearing age should use effective contraception while taking Vericiguat and for at least one month after discontinuing the medication.

What Other Drugs Will Affect Vericiguat

Vericiguat can interact with other medications, potentially altering its effectiveness or increasing the risk of side effects. One of the primary drug interactions to be aware of involves medications that also influence the NO-sGC-cGMP pathway. As previously mentioned, concurrent use of Vericiguat with nitrates (e.g., nitroglycerin) or PDE-5 inhibitors (e.g., sildenafil, tadalafil) is contraindicated due to the heightened risk of severe hypotension.

Other medications that can affect Vericiguat include certain antihypertensive drugs, such as alpha-blockers and calcium channel blockers, which can also lower blood pressure. When used in combination with Vericiguat, these medications may potentiate the risk of symptomatic hypotension. Therefore, healthcare providers should carefully monitor blood pressure and adjust dosages as necessary when these drugs are used together.

Additionally, some medications that influence liver enzymes, such as strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole) and inducers (e.g., rifampin, phenytoin), may affect the metabolism of Vericiguat. This can lead to altered plasma levels of Vericiguat and potentially impact its efficacy and safety profile. Patients should inform their healthcare provider of all medications they are taking, including over-the-counter drugs and supplements, to ensure proper management and avoid adverse interactions.

In conclusion, Vericiguat represents a significant advancement in the treatment of chronic heart failure with reduced ejection fraction. Its unique mechanism of action, focused on stimulating soluble guanylate cyclase, offers a novel therapeutic approach to improving cardiovascular outcomes in these patients. While Vericiguat is generally well-tolerated, patients should be aware of potential side effects and drug interactions. Adherence to the prescribed dosage regimen and regular monitoring by healthcare providers are essential to maximizing the benefits and minimizing the risks associated with Vericiguat therapy.