Verquvo (Vericiguat) for Symptomatic Chronic Heart Failure
Indication 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 worsening heart failure requiring hospitalization or outpatient IV diuretics. 1
Specific Patient Criteria
- LVEF <45% at time of treatment initiation 1, 2
- Recent worsening event defined as either:
- Elevated natriuretic peptides: BNP ≥300 pg/mL or NT-proBNP ≥1000 pg/mL (higher cutoffs with atrial fibrillation) 3
- NYHA class II to IV symptoms despite guideline-directed medical therapy 3, 2
Critical Exclusions
- Systolic blood pressure <100 mmHg (absolute contraindication) 3, 1
- Severe renal impairment (eGFR <15 mL/min/1.73 m²) 3
- Pregnancy (boxed warning for embryo-fetal toxicity) 1
- Concomitant use of other soluble guanylate cyclase stimulators 1
- Extremely elevated NT-proBNP >5314 pg/mL (no demonstrated benefit in this subgroup) 3
Dosing Protocol
Starting Dose
Begin with 2.5 mg orally once daily with food. 1
Titration Schedule
- Double the dose approximately every 2 weeks as tolerated 1
- Titration sequence: 2.5 mg → 5 mg → 10 mg once daily 1
- Target maintenance dose is 10 mg once daily 1, 2
Administration Details
- Must be taken with food 1
- For patients unable to swallow whole tablets, may crush and mix with water immediately before administration 1
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 3, 4. This leads to:
- Vasodilation
- Improved endothelial function
- Decreased fibrosis and cardiac remodeling 3
Critically, vericiguat does NOT directly enhance myocardial contractility and should not be confused with inotropic agents like dobutamine, milrinone, or levosimendan 5, 3.
Evidence-Based Outcomes
The VICTORIA trial (5,050 patients, median follow-up 10.8 months) demonstrated 2:
- 10% reduction in the composite primary outcome of cardiovascular death or heart failure hospitalization (35.5% vs 38.5%, HR 0.90,95% CI 0.82-0.98, p=0.02) 3, 2
- 10% reduction in any-cause death or heart failure hospitalization (37.9% vs 40.9%, HR 0.90,95% CI 0.83-0.98, p=0.02) 3, 2
- Non-significant trend toward reduced all-cause mortality (20.3% vs 21.2%, HR 0.95, p=0.38) 3
- 10% reduction in heart failure hospitalization (27.4% vs 29.6%, HR 0.90,95% CI 0.81-1.00) 3, 2
Safety Profile and Monitoring
Common Adverse Effects
- Hypotension: 16% with vericiguat vs 15% with placebo 1
- Anemia: 10% with vericiguat vs 7% with placebo 1
- Symptomatic hypotension: 9.1% vs 7.9% (not statistically significant) 3, 2
- Syncope: 4.0% vs 3.5% (not statistically significant) 3, 2
Blood Pressure Considerations
Patients with baseline systolic blood pressure ≥110 mmHg may experience a more pronounced initial decline in SBP over the first 16 weeks before returning to baseline levels 5, 3. Monitor blood pressure closely during titration, especially in the first 4 months.
Pregnancy Prevention Requirements (Boxed Warning)
- Obtain pregnancy test before initiating treatment in all females of reproductive potential 1
- Effective contraception required during treatment and for 1 month after stopping 1
- Do not administer to pregnant females due to risk of fetal harm 1
Place in Heart Failure Treatment Algorithm
Foundation Therapy First
Vericiguat should be added only after optimizing guideline-directed medical therapy (GDMT), which includes 6:
- ACE inhibitors or ARBs (if ACE-intolerant) 6
- Beta-blockers (bisoprolol, carvedilol, or metoprolol succinate) 6
- Diuretics for fluid management 6
- Aldosterone antagonists (spironolactone/eplerenone) for NYHA class III-IV 6
When to Add Vericiguat
Consider vericiguat as additional therapy for patients with HFrEF who remain symptomatic despite optimized GDMT and have experienced recent worsening requiring hospitalization or outpatient IV diuretics. 3 It represents a novel therapeutic option with a different mechanism of action from traditional heart failure medications 3.
Critical Pitfalls to Avoid
Do not use vericiguat as monotherapy or substitute for GDMT - it is an add-on therapy only 3
Do not confuse with inotropes - vericiguat does not increase contractility and should not be used for acute decompensated heart failure requiring inotropic support 5, 3
Avoid in patients with very high NT-proBNP (>5314 pg/mL) - this subgroup showed no benefit in VICTORIA 3
Do not combine with PDE-5 inhibitors - concomitant use is not recommended per FDA labeling 1
Monitor blood pressure closely during titration - particularly in patients with baseline SBP ≥110 mmHg who may experience initial declines 5, 3
Do not use with long-acting nitrates - contraindicated due to potential for excessive hypotension 5