What is the recommended dose of Vericiguat (Vericiguat) for heart failure treatment?

Vericiguat Dosing for Heart Failure Treatment

The recommended dosing regimen for vericiguat in heart failure treatment is to start at 2.5 mg once daily, titrate to 5 mg once daily after approximately 2 weeks, and then to the target dose of 10 mg once daily after another 2 weeks, as tolerated. 1

Dosing Protocol and Titration

• Vericiguat therapy should be initiated at 2.5 mg once daily and titrated at approximately 2-week intervals to 5 mg once daily, then to the target dose of 10 mg once daily, as tolerated 1
• The mean daily dose achieved in clinical trials was 9.2 mg 2
• Most patients (90%) in the pivotal VICTORIA trial achieved the 10 mg target dose after approximately 1 year of treatment 1

Patient Selection and Indications

• Vericiguat is indicated for selected high-risk patients with heart failure with reduced ejection fraction (HFrEF) and recent worsening of heart failure already on guideline-directed medical therapy (GDMT) 2
• Appropriate patients include those with:
  • LVEF <45%
  • NYHA class II-IV symptoms
  • On GDMT
  • Elevated natriuretic peptides (BNP ≥300 pg/mL or NT-proBNP ≥1000 pg/mL if in sinus rhythm; higher cutoffs with atrial fibrillation)
  • Recent heart failure worsening (hospitalized within 6 months or recently received IV diuretic therapy without hospitalization) 2

Contraindications and Precautions

• Vericiguat should be avoided in patients with:
  • Systolic blood pressure <100 mmHg
  • eGFR <15 mL/min/1.73 m²
  • Concomitant use of long-acting nitrates (limited experience)
  • Concomitant use of PDE-5 inhibitors (not recommended due to potential increased risk of hypotension) 2, 3

Clinical Efficacy

• In the VICTORIA trial, vericiguat demonstrated a 10% relative risk reduction in the primary outcome of cardiovascular death or heart failure hospitalization compared to placebo (HR 0.90,95% CI 0.82-0.98, p=0.019) 2, 1
• The annualized absolute risk reduction was 4.2% 1
• All-cause mortality occurred in 20.3% in the vericiguat group versus 21.2% in the placebo group (HR 0.95% CI 0.84-1.07, p=0.38) 2
• Composite of any-cause death or heart failure hospitalization was lower in the vericiguat group (HR 0.90,95% CI 0.83-0.98, p=0.02) 2

Monitoring and Adverse Effects

• Monitor for symptomatic hypotension, which occurred in 9.1% of patients on vericiguat versus 7.9% on placebo (p=0.12) 2, 4
• Watch for syncope, which occurred in 4.0% of patients on vericiguat versus 3.5% on placebo (p=0.30) 2, 4
• No clinically meaningful QT prolongation was observed with vericiguat 10 mg once daily at steady state 5
• No dose adjustments are necessary based on age, sex, race, or hepatic/renal impairment in adult patients with HFrEF 3

Important Clinical Considerations

• Patients in the highest quartile of NT-proBNP (>5314 pg/mL) did not show benefit from vericiguat compared to placebo 2
• Vericiguat has high oral bioavailability (93%) when taken with food 1, 3
• Administration with food increases vericiguat AUC by 44% and Cmax by 41% compared to fasted state 1
• The half-life of vericiguat is approximately 30 hours in patients with heart failure 1, 3
• Vericiguat can be administered as a whole tablet or crushed in water with comparable results 1

Mechanism of Action

• Vericiguat is a soluble guanylate cyclase (sGC) stimulator that directly binds and stimulates sGC, increasing cGMP production 2, 1
• cGMP has several potentially beneficial effects in heart failure, including vasodilation, improvement in endothelial function, and decrease in fibrosis and cardiac remodeling 2

By following this dosing protocol and carefully selecting appropriate patients, vericiguat can be effectively used as an additional therapy for patients with HFrEF who have had recent worsening despite GDMT.