What is Verquvo (vericiguat)?

What is Verquvo?

Verquvo (vericiguat) is an oral soluble guanylate cyclase (sGC) stimulator approved by the FDA to reduce the risk of cardiovascular death and heart failure hospitalization in adults with symptomatic chronic heart failure with ejection fraction less than 45% who have recently worsened despite guideline-directed medical therapy. 1, 2

Mechanism of Action

• Vericiguat directly binds and stimulates soluble guanylate cyclase (sGC), increasing cyclic guanosine monophosphate (cGMP) production independent of nitric oxide availability. 1, 3

• This increased cGMP leads to several beneficial cardiovascular effects including:

  • Vasodilation 1, 3
  • Improvement in endothelial function 1, 3
  • Reduction in cardiac fibrosis and adverse remodeling 1, 3

• Unlike traditional inotropic agents (dobutamine, milrinone), vericiguat does not directly enhance myocardial contractility, making it safer for long-term use without increasing cardiac oxygen demand. 4

FDA-Approved Indication

Verquvo is specifically indicated for high-risk patients who meet ALL of the following criteria: 1, 2

• Left ventricular ejection fraction (LVEF) <45% 1
• NYHA class II-IV symptoms 1
• Already on guideline-directed medical therapy (GDMT) 1
• Elevated natriuretic peptides: BNP ≥300 pg/mL or NT-proBNP ≥1000 pg/mL (higher cutoffs with atrial fibrillation) 1
• Recent heart failure worsening: hospitalization within 6 months OR recent outpatient IV diuretic therapy 1, 3

Clinical Evidence: The VICTORIA Trial

The pivotal VICTORIA trial demonstrated that vericiguat reduced the primary composite endpoint of cardiovascular death or first heart failure hospitalization by 10% compared to placebo (35.5% vs 38.5%, HR 0.90, p=0.019). 1, 3

• The composite of any-cause death or heart failure hospitalization was also reduced (HR 0.90,95% CI 0.83-0.98, p=0.02). 1, 3

• All-cause mortality alone showed a non-significant trend toward reduction (20.3% vs 21.2%, HR 0.95% CI 0.84-1.07, p=0.38). 1

• The relative risk reduction of 10% was lower than expected, even in this higher-risk population. 3

Dosing and Administration

• Take once daily with food. 2

• Tablets can be swallowed whole or crushed and mixed with water immediately before administration if unable to swallow whole. 2

• Available in 2.5 mg, 5 mg, and 10 mg tablets. 2

• The mean daily dose achieved in clinical trials was 9.2 mg. 5

• If a dose is missed, take it as soon as remembered on the same day; do not take two doses on the same day. 2

Absolute Contraindications

Do not prescribe Verquvo in patients with: 1, 2

• Systolic blood pressure <100 mmHg 1, 4
• Severe renal impairment (eGFR <15 mL/min/1.73 m²) 1, 4
• Concomitant use of other soluble guanylate cyclase stimulators 2
• Pregnancy 2
• Patients on long-acting nitrates 1

Important Safety Considerations

Patients with extremely elevated NT-proBNP levels (>5314 pg/mL, highest quartile) did not demonstrate benefit from vericiguat compared to placebo. 1, 3

Common Adverse Effects

• Hypotension (most common treatment-related adverse event) 6
• Anemia (low red blood cells) 2
• Symptomatic hypotension occurred in 9.1% vs 7.9% with placebo (not statistically significant) 1
• Syncope occurred in 4.0% vs 3.5% with placebo (not statistically significant) 1

Blood Pressure Effects

• Patients with baseline systolic blood pressure ≥110 mmHg may experience a more pronounced initial decline in blood pressure over the first 16 weeks before returning to baseline levels. 3, 4

Pregnancy and Reproductive Considerations

Verquvo may cause birth defects and is absolutely contraindicated in pregnancy. 2

• Females of reproductive potential must have a negative pregnancy test before starting therapy. 2
• Effective contraception is required during treatment and for 1 month after the final dose. 2
• Do not breastfeed while taking Verquvo. 2
• Healthcare providers should report any prenatal exposure by calling 1-877-888-4231 or at https://pregnancyreporting.verquvo-us.com. 2

Place in Heart Failure Treatment Algorithm

Vericiguat represents an additional therapeutic option for patients with HFrEF who remain symptomatic despite optimized GDMT, targeting a different pathophysiological mechanism (the NO-sGC-cGMP pathway) than traditional heart failure medications. 1, 3

• Current guideline-directed medical therapy for HFrEF includes ARNI/ACEI/ARB, beta-blockers, aldosterone antagonists, and SGLT2 inhibitors as first-line therapies. 1

• Vericiguat's place in GDMT is currently uncertain with limited regulatory approval, making widespread use in contemporary practice unrealistic at present. 1

Drug Interactions

Vericiguat has low drug-drug interaction potential. 7, 8

• No clinically relevant pharmacokinetic or pharmacodynamic interactions were observed with warfarin, digoxin, aspirin, or sacubitril/valsartan. 7

• Vericiguat is primarily metabolized by glucuronidation via UGT1A1 and UGT1A9 isoforms. 7

• Urinary excretion and renal clearance of vericiguat are low. 7

Storage

• Store at room temperature between 68°F to 77°F (20°C to 25°C). 2