What is the recommended use and dosage of Verquvo (vericiguat) for patients with symptomatic chronic heart failure?

Verquvo (Vericiguat) for Symptomatic Chronic Heart Failure

Recommended Use and Patient Selection

Verquvo is indicated to reduce the risk of cardiovascular death and heart failure hospitalization in adults with symptomatic chronic heart failure (NYHA class II-IV) and ejection fraction less than 45% who have recently experienced heart failure worsening—specifically following a hospitalization for heart failure or need for outpatient IV diuretics. 1

Specific Patient Criteria

The ideal candidate for Verquvo must meet ALL of the following:

• LVEF <45% 1
• Recent decompensation: Hospitalized for heart failure within the past 6 months OR received outpatient IV diuretic therapy 2, 3
• Elevated natriuretic peptides: BNP ≥300 pg/mL or NT-proBNP ≥1000 pg/mL (higher cutoffs if atrial fibrillation present) 2
• Already on guideline-directed medical therapy (ACE inhibitors/ARBs, beta-blockers, diuretics) 2, 4
• Systolic blood pressure ≥100 mmHg 2, 1
• eGFR ≥15 mL/min/1.73 m² 2

Important Patient Selection Caveat

Patients with extremely elevated NT-proBNP levels (>5314 pg/mL) did NOT show benefit from vericiguat compared to placebo, suggesting this medication works best in high-risk but not end-stage patients. 2

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Dosing Protocol

Starting Dose

Begin with 2.5 mg orally once daily with food. 1

Titration Schedule

Double the dose approximately every 2 weeks to reach the target maintenance dose of 10 mg once daily, as tolerated:

• Week 0-2: 2.5 mg once daily
• Week 2-4: 5 mg once daily
• Week 4+: 10 mg once daily (target dose) 1

Administration Details

• Must be taken with food 1
• For patients unable to swallow tablets: crush and mix with water immediately before administration 1

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Mechanism and Clinical Benefits

How Vericiguat Works

Vericiguat is a soluble guanylate cyclase (sGC) stimulator that directly binds and stimulates sGC, increasing cyclic guanosine monophosphate (cGMP) production. 2, 5 This leads to:

• Vasodilation
• Improved endothelial function
• Decreased cardiac fibrosis and remodeling 2

Critical distinction: Vericiguat does NOT directly enhance myocardial contractility like true inotropes (dobutamine, milrinone, levosimendan), making it safer for long-term use but inappropriate for acute decompensation requiring increased cardiac contractility. 6, 2

Evidence-Based Outcomes

The VICTORIA trial (5,050 patients, median follow-up 10.8 months) demonstrated:

• 10% reduction in the composite of cardiovascular death or heart failure hospitalization (35.5% vs 38.5%, HR 0.90, p=0.019) 2, 3
• Reduction in any-cause death or heart failure hospitalization (HR 0.90,95% CI 0.83-0.98, p=0.02) 2, 3
• Non-significant trend toward reduced all-cause mortality (20.3% vs 21.2%, HR 0.95, p=0.38) 2, 3

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Contraindications and Safety

Absolute Contraindications

• Pregnancy (causes fetal harm—BOXED WARNING) 1
• Concomitant use of other sGC stimulators 1
• Systolic blood pressure <100 mmHg 2
• Severe renal impairment (eGFR <15 mL/min/1.73 m²) 2

Pregnancy Prevention Requirements

For all females of reproductive potential:

1. Obtain pregnancy test BEFORE starting treatment 1
2. Use effective contraception during treatment AND for 1 month after stopping 1

Common Adverse Effects

The most frequent adverse reactions (≥5% and more common than placebo):

• Hypotension: 16% vs 15% with placebo 1
• Anemia: 10% vs 7% with placebo 1
• Symptomatic hypotension: 9.1% vs 7.9% (not statistically significant) 2, 3
• Syncope: 4.0% vs 3.5% 2, 3

Blood Pressure Monitoring

Patients with baseline SBP ≥110 mmHg may experience a more pronounced initial decline in systolic blood pressure over the first 16 weeks before returning to baseline levels. 6, 2 Monitor blood pressure closely during titration.

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Place in Heart Failure Treatment Algorithm

Verquvo should be considered as add-on therapy for patients with HFrEF who remain symptomatic despite optimized guideline-directed medical therapy (ACE inhibitors/ARBs, beta-blockers, mineralocorticoid receptor antagonists, diuretics). 2, 4

This represents a novel therapeutic option with a different mechanism of action from traditional heart failure medications, specifically targeting the impaired nitric oxide-sGC-cGMP pathway. 2, 5

When to Consider Verquvo

Add vericiguat when a patient on optimal medical therapy experiences:

• Recent heart failure hospitalization (within 6 months), OR
• Need for outpatient IV diuretics 2, 1

Do NOT use vericiguat as monotherapy—it must be added to existing guideline-directed medical therapy. 4

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Drug Interactions

Not Recommended

Concomitant use with PDE-5 inhibitors is not recommended due to potential additive vasodilatory effects. 1

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Clinical Pearls and Common Pitfalls

Key Considerations

• Vericiguat is NOT an inotrope: Do not use for acute decompensated heart failure requiring increased contractility 6, 2
• The 10% relative risk reduction was modest even in this high-risk population, so set realistic expectations 2
• Safe in reduced renal function (down to eGFR 15 mL/min/1.73 m²) 7
• No dose adjustments needed based on age, sex, race, or mild-to-moderate renal impairment 8

Avoid These Mistakes

• Starting vericiguat in patients with SBP <100 mmHg (contraindicated) 2, 1
• Using in patients with extremely elevated NT-proBNP (>5314 pg/mL)—no proven benefit 2
• Forgetting pregnancy testing and contraception counseling in females of reproductive potential 1
• Confusing vericiguat with inotropic agents for acute management 6