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

Vericiguat for Heart Failure with Reduced Ejection Fraction

Recommended Use and Patient Selection

Vericiguat is indicated for patients with LVEF <45% and NYHA class II-IV symptoms who have experienced recent heart failure worsening—defined as hospitalization within 6 months or outpatient IV diuretic use—and have elevated natriuretic peptides (BNP ≥300 pg/mL or NT-proBNP ≥1000 pg/mL in sinus rhythm), on top of optimal guideline-directed medical therapy. 1

This represents a Class 2b recommendation from major heart failure societies, positioning vericiguat as a therapy for high-risk patients who remain symptomatic despite foundational treatments including ARNI/ACE inhibitor/ARB, beta-blocker, mineralocorticoid receptor antagonist, and SGLT2 inhibitor. 1

Critical Patient Selection Criteria

• Recent worsening event required: The FDA approval and guideline recommendations specifically require either HF hospitalization within 6 months OR need for outpatient IV diuretics. 1, 2
• Elevated natriuretic peptides mandatory: BNP ≥300 pg/mL or NT-proBNP ≥1000 pg/mL (in sinus rhythm) must be documented. 1
• LVEF threshold: Must be <45% (FDA label states <45%, though some guidelines reference <40%). 1, 2

Absolute Contraindications

• Systolic blood pressure <100 mmHg: This is a critical safety threshold. 1
• Severe renal impairment: eGFR <15 mL/min/1.73m². 1
• Concomitant long-acting nitrates: Avoid due to potential for excessive hypotension. 1
• Pregnancy: Boxed warning for embryo-fetal toxicity—exclude pregnancy before starting and ensure effective contraception during treatment and for one month after stopping. 2
• Concomitant use with other sGC stimulators: Absolute contraindication. 2

Dosing Algorithm

Starting Dose

Begin with vericiguat 2.5 mg orally once daily with food. 2

• Tablets may be crushed and mixed with water for patients with swallowing difficulties. 2
• Must be taken with food to optimize absorption. 2

Titration Schedule

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

• Titration pathway: 2.5 mg → 5 mg → 10 mg (target dose)
• Each dose increase occurs at 2-week intervals if tolerated. 2
• The 10 mg dose provides maximum benefit, with approximately 90% of patients in the VICTORIA trial achieving this target dose. 3

Managing Hypotension During Titration

• Symptomatic hypotension is the most common adverse event (11.3% vs 9.2% with placebo). 2, 4
• If symptomatic hypotension occurs, consider reducing diuretic doses first before reducing vericiguat. 4
• Asymptomatic low blood pressure alone should not prevent titration if perfusion is adequate. 4
• The drug shows consistent efficacy across the spectrum of baseline systolic blood pressure, including those with SBP ≤110 mmHg. 4

Clinical Efficacy and Place in Therapy

Evidence Base

Vericiguat reduces the composite outcome of cardiovascular death or heart failure hospitalization by 10% compared to placebo (HR 0.90, p=0.019), with a number needed to treat of approximately 24-33 patients to prevent one primary outcome event. 1, 3

• This represents an absolute event-rate reduction of 4.2 events per 100 patient-years. 3
• The benefit was demonstrated in the VICTORIA trial, which enrolled particularly high-risk patients with recent worsening. 1, 3

Critical Context: Recent VICTOR Trial Results

Important caveat: The 2025 VICTOR trial demonstrated that vericiguat does NOT reduce the primary composite endpoint in patients with HFrEF who have NOT had recent worsening (HR 0.93,95% CI 0.83-1.04, p=0.22). 5

• This confirms that vericiguat's benefit is specifically in the high-risk, recently decompensated population. 5
• Nominally fewer cardiovascular deaths occurred in VICTOR (HR 0.83), but this was not the primary endpoint and requires cautious interpretation. 5
• Clinical implication: Do not use vericiguat in stable HFrEF patients without recent worsening—the indication is specifically for those with recent hospitalization or IV diuretic use. 1, 5

Positioning in the Treatment Algorithm

Vericiguat should be considered for patients with HFrEF who remain symptomatic despite optimal treatment with foundational therapies (ARNI/ACE inhibitor/ARB, beta-blocker, MRA, and SGLT2 inhibitor) AND who have had recent worsening. 1

Hierarchy of HFrEF Therapy

1. First-line quadruple therapy: SGLT2 inhibitor + MRA + beta-blocker + ARNI (or ACE inhibitor/ARB) 6
2. Optimize doses of all four foundational medications 6
3. Add vericiguat if patient has recent worsening event and remains symptomatic despite optimized foundational therapy 1

Key Distinction from Other Add-On Therapies

• Ivabradine: For patients with heart rate ≥70 bpm in sinus rhythm despite maximally tolerated beta-blocker 6
• Hydralazine/isosorbide dinitrate: For self-identified Black patients with NYHA class III-IV symptoms 6
• Vericiguat: Specifically for those with recent worsening event (hospitalization or IV diuretics within 6 months) 1

Safety Monitoring

Common Adverse Events

• Hypotension (most common, occurring in ≥5% of patients) 2
• Anemia (occurring in ≥5% of patients) 2
• Syncope (4% vs 3.5% with placebo, p=0.03) 7

Special Populations

• Older patients (>75 years): Similar blood pressure trajectories and symptomatic hypotension rates as younger patients—age alone should not preclude use. 4
• Patients on ARNI or SGLT2i: Vericiguat is well-tolerated even when combined with these contemporary therapies. 4
• Reduced renal function: The drug has shown safety in patients with reduced renal function, though severe impairment (eGFR <15) is a contraindication. 1, 7

Reproductive Considerations

• Females of reproductive potential: Must exclude pregnancy before starting treatment. 2
• Contraception required: Effective contraception must be used during treatment and for one month after stopping. 2
• Breastfeeding: Not recommended. 2

Common Pitfalls to Avoid

• Using vericiguat in stable patients without recent worsening: The VICTOR trial clearly shows no benefit in this population—stick to the indication. 5
• Withholding due to asymptomatic low blood pressure: Efficacy is maintained across blood pressure ranges; focus on symptoms and perfusion, not numbers alone. 4
• Failing to titrate to target dose: The 10 mg dose provides maximum benefit—titrate aggressively unless symptomatic issues arise. 3
• Combining with long-acting nitrates: This is contraindicated due to hypotension risk. 1
• Starting in patients with SBP <100 mmHg: This violates guideline recommendations and increases hypotension risk. 1