Vericiguat, sold under the brand name Verquvo, is a medication used to reduce the risk of cardiovascular death and hospitalization in certain patients with

heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...

after a recent acute decompensation event. It is taken by mouth. Vericiguat is a soluble guanylate cyclase (sGC) stimulator. Common side effects include low blood pressure and low red cell count ( anemia). It was approved for medical use in the United States in January 2021, and for use in the European Union in July 2021. The U.S. Food and Drug Administration considers it to be a first-in-class medication.

Medical uses

Vericiguat is

indicated In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosis ...

to reduce the risk of cardiovascular death and hospitalization for heart failure following a prior hospitalization for heart failure or need for outpatient

intravenous Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...

diuretics, in adults with symptomatic chronic heart failure and an ejection fraction of less than 45%.

Adverse effects

Vericiguat causes harm to the unborn baby and should not be given to pregnant women. It is not known to what extent vericiguat passes into

breastmilk Breast milk (sometimes spelled as breastmilk) or mother's milk is milk produced by mammary glands located in the breast of a human female. Breast milk is the primary source of nutrition for newborns, containing fat, protein, carbohydrates (lactos ...

; therefore, breastfeeding patients should not take vericiguat. The most common side effects of vericiguat include low blood pressure and anemia. Patients taking other soluble guanylate cyclase inhibitors should not take vericiguat.

Pharmacology

Vericiguat is a direct stimulator of soluble guanylate cyclase, an important enzyme in vascular

smooth muscle Smooth muscle is an involuntary non-striated muscle, so-called because it has no sarcomeres and therefore no striations (''bands'' or ''stripes''). It is divided into two subgroups, single-unit and multiunit smooth muscle. Within single-unit mus ...

cells. Specifically, vericiguat binds to the beta-subunit of the target site on the soluble guanylate cyclase enzyme. Soluble guanylate cyclase catalyzes the formation of

cyclic GMP Cyclic guanosine monophosphate (cGMP) is a cyclic nucleotide derived from guanosine triphosphate (GTP). cGMP acts as a second messenger much like cyclic AMP. Its most likely mechanism of action is activation of intracellular protein kinases in re ...

upon interaction with

nitric oxide Nitric oxide (nitrogen oxide or nitrogen monoxide) is a colorless gas with the formula . It is one of the principal oxides of nitrogen. Nitric oxide is a free radical: it has an unpaired electron, which is sometimes denoted by a dot in its che ...

to activate a number of downstream

signaling cascade A biochemical cascade, also known as a signaling cascade or signaling pathway, is a series of chemical reactions that occur within a biological cell when initiated by a stimulus. This stimulus, known as a first messenger, acts on a receptor that ...

s, which can compensate for defects in this pathway and resulting losses in regulatory myocardial and vascular cellular processes due to cardiovascular complications.

Pharmacokinetics

After vericiguat is administered (100 mg by mouth once daily), the average steady state and Cmax and AUC for patients with cardiovascular failure is 350 mcg/L and 6,680 mcg/h/L with a Tmax of one hour. Vericiguat has a positive food effect, and therefore patients are advised to consume food with the drug for an oral bioavailability of 93%. Vericiguat is extensively protein bound in plasma. Vericiguat is primarily metabolized via phase 2 conjugation reactions, with a minor CYP-mediated oxidative metabolite. The major

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

is glucuronidated and inactive. The typical half-life profile for patients with heart failure is 30 hours. Vericiguat has a decreased clearance in patients with systolic heart failure.

History

The U.S. Food and Drug Administration (FDA) approved vericiguat based on evidence from a clinical trial (NCT02861534) which consisted of 5,050 participants aged 23 to 98 years old with worsening heart failure. The trial was conducted at 694 sites in 42 countries in Europe, Asia, North and South America. The trial enrolled participants with symptoms of worsening heart failure. Participants were randomly assigned to receive vericiguat or a placebo pill once a day. Neither the participants nor the health care professionals knew if the participants were given vericiguat or placebo pill until after the trial was complete. It was awarded a fast track designation on 19 January 2021.

Society and culture

Legal status

On 20 May 2021, the Committee for Medicinal Products for Human Use (CHMP) of the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Euro ...

(EMA) adopted a positive opinion, recommending the granting of a marketing authorization for vericiguat, intended for the treatment of symptomatic chronic heart failure in adults with reduced ejection fraction. The applicant for this medicinal product is Bayer AG. Vericiguat was approved for medical use in the European Union in July 2021.

References

External links

* * {{Portal bar , Medicine Vasodilators Pyrazolopyridines Fluoroarenes Pyrimidines Carbamates Amines Merck & Co. brands