|Drug class||Soluble guanylate cyclase activator|
|Main uses||Heart failure|
|Side effects||Low blood pressure, low red blood cells|
|Typical dose||10 mg OD|
|Chemical and physical data|
|Molar mass||426.388 g·mol−1|
|3D model (JSmol)|
Vericiguat, sold under the brand name Verquvo, is a medication used in heart failure after a recent worsening to reduce the risk of heart related death and hospitalization. It is only used in those with an ejection fraction less than 45%. It is taken by mouth.
Common side effects include low blood pressure and low red blood cells. Use in pregnancy may harm the baby. It is a soluble guanylate cyclase (sGC) stimulator, and should not be used with other medications in this class.
Vericiguat was approved for medical use in the United States and Europe in 2021. In the United States it costs about 615 USD per month as of 2022. This amount in the United Kingdom costs the NHS about £100.
Vericiguat is used to reduce the risk of cardiovascular death and hospitalization for heart failure following a prior hospitalization for heart failure or need for outpatient intravenous diuretics, in adults with symptomatic chronic heart failure and an ejection fraction of less than 45%. It decreases this risk from 38.5% to 35.5% over a year.
It is started at 2.5 mg once per day and may be doubled every 2 weeks to a typical dose of 10 mg once per day.
Vericiguat may cause harm to the unborn baby and should not be given to pregnant women. It is also not known how vericiguat passes into breastmilk, therefore 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 also not be taking vericiguat.
Vericiguat is a direct stimulator of soluble guanylate cyclase enzyme, an important enzyme in vascular smooth muscle cells. Specifically, vericiguat will bind to the beta-subunit of the target site on the soluble guanylate cyclase enzyme. Soluble guanylate cyclase enzymes catalyzes the formation of cyclic GMP upon interaction with nitric oxide to activate a number of downstream signaling cascade which can compensate for defects in this pathway and resulting losses in regulatory myocardial and vascular cellular processes due to cardiovascular complications. 
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 II conjugation reactions, with a minor CYP-mediated oxidative metabolite. The major metabolite is glucuronidated and inactive. The typical half-life profile for patients with heart failure is 30 hours. Vericiguat has a decreased clearance and was observed to have a 1.6 g/L clearance in patients with systolic heart failure. 
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 January 19th, 2021. 
Society and culture
On 20 May 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (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.
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