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 after a recent acute decompensation event.[3][4][8] It is taken by mouth.[3][4][8] Vericiguat is a soluble guanylate cyclase (sGC) stimulator.[3]
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Trade names | Verquvo |
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Routes of administration | By mouth |
Drug class | Soluble guanylate cyclase activator |
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ECHA InfoCard | 100.247.370 |
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Formula | C19H16F2N8O2 |
Molar mass | 426.388 g·mol−1 |
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Common side effects include low blood pressure and low red cell count (anemia).[4][8]
It was approved for medical use in the United States in January 2021,[4][9] and for use in the European Union in July 2021.[8] The U.S. Food and Drug Administration considers it to be a first-in-class medication.[10]
Vericiguat is indicated 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%.[3][4]
Vericiguat causes harm to the unborn baby and should not be given to pregnant women.[4] It is not known to what extent vericiguat passes into breastmilk; therefore, breastfeeding patients should not take vericiguat.
The most common side effects of vericiguat include low blood pressure and anemia.[3] Patients taking other soluble guanylate cyclase inhibitors should not take vericiguat.[3]
Vericiguat is a direct stimulator of soluble guanylate cyclase, an important enzyme in vascular smooth muscle cells. Specifically, vericiguat binds to the beta-subunit of the target site on the soluble guanylate cyclase enzyme.[11] Soluble guanylate cyclase catalyzes the formation of cyclic GMP upon interaction with nitric oxide to activate a number of downstream signaling cascades, which can compensate for defects in this pathway and resulting losses in regulatory myocardial and vascular cellular processes due to cardiovascular complications.[11][vague][clarification needed]
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%.[11] Vericiguat is extensively protein bound in plasma.[11] Vericiguat is primarily metabolized via phase 2 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 in patients with systolic heart failure. [11]
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.[4] The trial was conducted at 694 sites in 42 countries in Europe, Asia, North and South America.[4] The trial enrolled participants with symptoms of worsening heart failure.[4] Participants were randomly assigned to receive vericiguat or a placebo pill once a day.[4] Neither the participants nor the health care professionals knew if the participants were given vericiguat or placebo pill until after the trial was complete.[4] It was awarded a fast track designation on 19 January 2021. [12]
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.[13] The applicant for this medicinal product is Bayer AG. Vericiguat was approved for medical use in the European Union in July 2021.[8][14]