What are the benefits of Verquvo (vericiguat) for patients with Congestive Heart Failure (CHF)?

Benefits of Verquvo (Vericiguat) for Patients with Congestive Heart Failure

Vericiguat significantly reduces the risk of cardiovascular death and heart failure hospitalization by 10% in patients with symptomatic chronic heart failure with ejection fraction less than 45% who have had recent heart failure worsening. 1

Mechanism of Action and Indications

• Vericiguat is an oral soluble guanylyl cyclase (sGC) stimulator that directly binds and stimulates sGC, increasing cyclic guanosine monophosphate (cGMP) production 1
• cGMP has several beneficial effects in heart failure patients, including vasodilation, improvement in endothelial function, and decrease in fibrosis and cardiac remodeling 1
• FDA-approved to reduce the risk of cardiovascular death and heart failure hospitalization in adults with symptomatic chronic heart failure with ejection fraction less than 45% following hospitalization for heart failure or need for outpatient IV diuretics 2

Clinical Benefits Based on VICTORIA Trial

• In the VICTORIA trial of 5,050 high-risk patients with worsening HFrEF, vericiguat demonstrated:
  • 10% reduction in the primary composite outcome of cardiovascular death or heart failure hospitalization compared to placebo (35.5% vs 38.5%, HR 0.90, p=0.019) 1
  • Reduction in the composite of any-cause death or heart failure hospitalization (HR 0.90,95% CI 0.83-0.98, p=0.02) 1
  • Non-significant trend toward reduction in all-cause mortality (20.3% vs 21.2%, HR 0.95% CI 0.84-1.07, p=0.38) 1

Patient Selection for Optimal Benefit

• Most appropriate for patients with:
  • LVEF <45% 2
  • NYHA class II to IV symptoms 1
  • Already on guideline-directed medical therapy (GDMT) 3
  • Elevated natriuretic peptides (BNP ≥300 pg/mL or NT-proBNP ≥1000 pg/mL if in sinus rhythm; higher cutoffs with AF) 1
  • Recent heart failure worsening (hospitalized within 6 months or recently received IV diuretic therapy without hospitalization) 1

Important Considerations and Precautions

• Patients with extremely elevated NT-proBNP levels (>5314 pg/mL) did not show benefit from vericiguat compared to placebo 1
• Contraindicated in patients with:
  • Concomitant use of other soluble guanylate cyclase stimulators 2
  • Systolic blood pressure <100 mmHg 1, 4
  • Severe renal impairment (eGFR <15 mL/min/1.73 m²) 1
  • Pregnancy (due to embryo-fetal toxicity) 2
• Common adverse effects include:
  • Hypotension (16% vs 15% with placebo) 2
  • Anemia (10% vs 7% with placebo) 2
  • Symptomatic hypotension (9.1% vs 7.9%) and syncope (4.0% vs 3.5%), though not statistically significant 1

Dosing Recommendations

• Starting dose: 2.5 mg orally once daily with food 2
• Dose titration: Double the dose approximately every 2 weeks to reach target maintenance dose of 10 mg once daily, as tolerated 2
• For patients unable to swallow tablets, they may be crushed and mixed with water immediately before administration 2

Place in Heart Failure Treatment Algorithm

• Vericiguat should be considered as an additional therapy for patients with HFrEF who remain symptomatic despite optimized GDMT 3, 5
• It represents a novel therapeutic option with a different mechanism of action from traditional heart failure medications 6
• Current guidelines position vericiguat as an additional medical therapy that may be considered for patients with HFrEF who have had recent worsening despite GDMT 1

Clinical Pearls

• Blood pressure effects: Patients with baseline SBP ≥110 mmHg may experience a more pronounced initial decline in SBP with vericiguat over the first 16 weeks before returning to baseline levels 1, 4
• Unlike inotropic agents, vericiguat does not directly enhance myocardial contractility, making it safer for long-term use 4
• The relative risk reduction of 10% in the primary outcome was lower than expected, even in a higher-risk population 1
• Vericiguat represents a novel approach to heart failure treatment by targeting the NO-sGC-cGMP pathway that is disrupted in heart failure 6, 7