Vericiguat (Verquvo) for Heart Failure
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Vericiguat (Verquvo) for Heart Failure
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Med Lett Drugs Ther. 2021 Mar 8;63(1619):36-7
 Select a term to see related articles  ACE inhibitors   Adempas   ARBs   Beta blockers   BiDil   Bisoprolol   Carvedilol   dapagliflozin   Diuretics   empagliflozin   Entresto   Eplerenone   Heart Failure   Hydralazine   Isosorbide dinitrate   Metoprolol   riociguat   sacubitril   Spironolactone   Valsartan   vericiguat   Verquvo 
Summary: Vericiguat (Verquvo)
  • First soluble guanylate cyclase (sGC) stimulator to be approved for chronic heart failure.
  • FDA-approved to reduce the risk of hospitalization for heart failure and cardiovascular (CV) death following a worsening heart failure event in patients with symptomatic chronic heart failure and an ejection fraction <45%.
  • In one clinical trial, addition of vericiguat modestly reduced the risk of a composite endpoint of CV death and first hospitalization for heart failure compared to placebo.

The FDA has approved vericiguat (Verquvo – Merck), an oral soluble guanylate cyclase (sGC) stimulator, to reduce the risk of hospitalization for heart failure and cardiovascular (CV) death following a worsening heart failure event (hospitalization for heart failure or treatment with IV diuretics as an outpatient) in patients with symptomatic chronic heart failure and left ventricular ejection fraction (LVEF) <45%. Vericiguat is the second sGC stimulator to be marketed in the US. Riociguat (Adempas), which is FDA-approved for treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension, was the first.1

STANDARD TREATMENT — Patients with heart failure and a LVEF ≤40% are considered to have heart failure with reduced ejection fraction (HFrEF). Guidelines now recommend that all patients with HFrEF take an angiotensin receptor-neprilysin inhibitor (ARNI; sacubitril/valsartan); an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) can be used in patients who are unable to tolerate an ARNI. Patients should also take an evidence-based beta blocker (i.e., carvedilol, metoprolol succinate, bisoprolol) and, if volume overloaded, a diuretic. A mineralocorticoid receptor antagonist (i.e., spironolactone, eplerenone) and a sodium-glucose cotransporter 2 (SGLT2) inhibitor (i.e., dapagliflozin, empagliflozin) should be added in patients who do not have severe renal impairment.2-5 In black patients with NYHA class III-IV symptoms, addition of hydralazine/isosorbide dinitrate should be considered. The If channel inhibitor ivabradine is a second-line option for some patients.6

MECHANISM OF ACTION — Heart failure is associated with reduced synthesis and increased breakdown of nitric oxide (NO) and decreased sGC activity. Binding of NO to sGC increases production of cyclic guanosine monophosphate (cGMP), which leads to smooth muscle relaxation and vasodilation. Vericiguat binds to and stimulates sGC independently of and combined with endogenous NO.

CLINICAL STUDIES — FDA approval of vericiguat was based on the results of a double-blind trial (VICTORIA) in 5050 patients with symptomatic chronic heart failure (NYHA class II-IV) and a LVEF <45% who had been hospitalized for heart failure within the previous 6 months or required outpatient treatment with IV diuretics within the previous 3 months. Patients were randomized to receive vericiguat (target dosage of 10 mg once daily) or placebo, each added to a standard heart failure therapy (only 15% of patients were taking an ARNI). After a median of 10.8 months, significantly fewer patients treated with vericiguat had a primary outcome event (composite of CV death or first hospitalization for heart failure) compared to those who received placebo (HR 0.90, 95% CI: 0.82-0.98). Based on the absolute risk reduction of 4.2 events per 100 patient-years, the number needed to treat is 24 patients. When CV death and first hospitalization for heart failure were evaluated as separate endpoints, the differences between vericiguat and placebo were not statistically significant (HR 0.93, 95% CI: 0.81-1.06 and HR 0.90, 95% CI: 0.81-1.00, respectively).7 VICTORIA trial results are summarized in Table 2.

ADVERSE EFFECTS — In VICTORIA, anemia occurred in 10% of patients who received vericiguat compared to 7% of those who received placebo. There were no significant differences between the two groups in the rates of symptomatic hypotension or syncope.

DRUG INTERACTIONS — Because of a possible increased risk of hypotension, concomitant use of vericiguat and phosphodiesterase-5 (PDE5) inhibitors such as sildenafil (Viagra, and others) is not recommended.

PREGNANCY AND LACTATION — Vericiguat is contraindicated for use during pregnancy. In animal studies, administration of vericiguat to pregnant rats and rabbits at levels 4-24 times the maximum recommended human exposure resulted in malformations of the heart and major vessels, increased abortions and resorptions, decreased pup weight, and increased mortality. An effective form of contraception is recommended during treatment and for 1 month after stopping vericiguat.

Vericiguat is present in the milk of lactating rats and it is likely that the drug or its metabolites will be present in human breast milk. Women should be advised not to breastfeed while taking the drug.

DOSAGE, ADMINISTRATION, AND COST — The recommended starting dosage of vericiguat is 2.5 mg taken once daily with food; the daily dose should be doubled every 2 weeks as tolerated up to a target of 10 mg. A 30-day supply of vericiguat costs $582.90.8

CONCLUSION — In patients with heart failure with reduced ejection fraction (HFrEF) who had recently been hospitalized for heart failure or required outpatient treatment with an IV diuretic, addition of vericiguat (Verquvo) to standard therapy modestly reduced the risk of a composite endpoint of death from cardiovascular causes or first hospitalization for heart failure after a median of 10.8 months. The efficacy of the drug in patients taking an optimized heart failure regimen that includes sacubitril/valsartan (Entresto) and an SGLT2 inhibitor is unknown. Long-term efficacy data are needed.

Additional Content: Comparison Table: Some Drugs for HFrEF

REFERENCES

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