What is the recommended dosing and management of Veruciguat (Vericiguat) for patients with heart failure with reduced ejection fraction?

Vericiguat Dosing and Management for Heart Failure with Reduced Ejection Fraction

Vericiguat is recommended at a starting dose of 2.5 mg orally once daily with food, doubled approximately every 2 weeks to reach the target maintenance dose of 10 mg once daily, for patients with symptomatic chronic heart failure with ejection fraction less than 45% who have had a recent heart failure hospitalization or received outpatient IV diuretics. 1

Indication and Patient Selection

• Vericiguat (Verquvo) is a soluble guanylate cyclase (sGC) stimulator indicated to reduce the risk of cardiovascular death and heart failure hospitalization in adults with symptomatic chronic HF with ejection fraction less than 45% following a hospitalization for heart failure or need for outpatient IV diuretics 1
• Patients most likely to benefit have:
  • LVEF <45% with NYHA class II-IV symptoms 2
  • Recent heart failure worsening (hospitalized within 6 months or received IV diuretics without hospitalization) 2
  • Elevated natriuretic peptides (BNP ≥300 pg/mL or NT-proBNP ≥1000 pg/mL in sinus rhythm; higher cutoffs with AF) 2

Dosing Protocol

• Starting dose: 2.5 mg orally once daily with food 1
• Titration schedule: Double the dose approximately every 2 weeks to reach target dose 1
• Target maintenance dose: 10 mg once daily, as tolerated by the patient 1
• For patients with difficulty swallowing, tablets may be crushed and mixed with water 1

Monitoring and Safety Considerations

• Blood pressure monitoring: Vericiguat causes a mean reduction in systolic blood pressure of approximately 1-2 mm Hg compared to placebo 1
• Pregnancy testing: Must verify pregnancy status in females of reproductive potential before initiating therapy due to potential fetal harm (Boxed Warning) 1
• Common adverse effects to monitor for:
  • Hypotension (9.1% vs 7.9% with placebo) 2, 3
  • Syncope (4.0% vs 3.5% with placebo) 2, 3
  • Anemia (reported in ≥5% of patients) 1

Contraindications

• Pregnancy (Boxed Warning) - may cause fetal harm 1
• Concomitant use of other soluble guanylate cyclase (sGC) stimulators 1
• Systolic blood pressure <100 mm Hg 2
• Severe renal impairment (eGFR <15 mL/min/1.73m²) 2
• Concomitant use with long-acting nitrates is not recommended 2

Special Populations

• Geriatric patients: No dosage adjustment required for elderly patients 1
• Renal impairment: No dosage adjustment needed for patients with eGFR ≥15 mL/min/1.73m² who are not on dialysis 1
• Hepatic impairment: No dosage adjustment needed for mild to moderate hepatic impairment (Child-Pugh A or B); not studied in severe hepatic impairment 1
• Women of reproductive potential: Must use effective contraception during treatment and for one month after the final dose 1

Clinical Efficacy

• In the VICTORIA trial, vericiguat reduced the primary outcome of cardiovascular death or heart failure hospitalization by 10% compared to placebo (HR 0.90, p=0.019) 2, 3
• The number needed to treat was approximately 33 patients to prevent one primary outcome event 2
• Patients with extremely elevated NT-proBNP levels (>5314 pg/mL) did not show benefit from vericiguat compared to placebo 2
• The VICTOR trial showed that in stable HFrEF patients without recent worsening, vericiguat did not significantly reduce the primary composite endpoint but did reduce cardiovascular deaths 4, 5

Place in Therapy

• Vericiguat should be considered for patients with HFrEF who remain symptomatic despite optimal treatment with foundational therapies 2
• It is positioned as an additional therapy after patients are already on guideline-directed medical therapy including:
  • ACE inhibitor/ARB/ARNI
  • Beta-blocker
  • Mineralocorticoid receptor antagonist
  • SGLT2 inhibitor 2
• The 2022 AHA/ACC/HFSA guidelines give vericiguat a Class 2b recommendation for patients with HFrEF who have had a recent hospitalization or IV diuretic treatment 2

Important Prescribing Considerations

• Vericiguat works by stimulating soluble guanylate cyclase (sGC), which increases intracellular cyclic guanosine monophosphate (cGMP) levels, leading to smooth muscle relaxation and vasodilation 1, 6
• Vericiguat demonstrates a dose-dependent reduction in NT-proBNP, a biomarker in heart failure 1
• No clinically meaningful QTc prolongation has been observed with vericiguat 10 mg 1