What is the role of Vericiguat (vericiguat) in the management of heart failure, particularly in patients with reduced ejection fraction?

Role of Vericiguat in Heart Failure Management

Vericiguat is indicated to reduce the risk of cardiovascular death and heart failure hospitalization following a hospitalization for heart failure or need for outpatient IV diuretics, in adults with symptomatic chronic heart failure with ejection fraction less than 45%. 1

Mechanism of Action and Positioning in Therapy

Vericiguat works through a novel mechanism as a soluble guanylate cyclase (sGC) stimulator. It:

• Enhances cyclic guanosine monophosphate (cGMP) production
• Promotes vasodilation and improved endothelial function
• Decreases fibrosis and cardiac remodeling 2

The American College of Cardiology recommends vericiguat as an additional option for patients who:

• Continue to have symptoms despite optimal guideline-directed medical therapy (GDMT)
• Have recently experienced worsening heart failure 2

Evidence for Efficacy

The VICTORIA trial demonstrated that vericiguat:

• Reduced 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) 2
• Was most effective in patients with lower N-terminal pro-brain natriuretic peptide levels 2
• Was less effective in patients with extremely elevated biomarker levels 2

Patient Selection and Dosing

Appropriate Candidates:

• Adults with symptomatic chronic HF with EF <45% 1
• Patients who have had a recent HF hospitalization or needed outpatient IV diuretics 1
• Patients who remain symptomatic despite standard GDMT 3

Dosing:

• Starting dose: 2.5 mg orally once daily with food
• Titration: Double the dose approximately every 2 weeks
• Target maintenance dose: 10 mg once daily, as tolerated 1

Safety Considerations

Monitor for:

• Symptomatic hypotension (9.1% vs 7.9% with placebo) 2
• Syncope (4.0% vs 3.5% with placebo) 2
• Anemia (10% vs 7% with placebo) 1

Contraindications:

• Pregnancy (embryo-fetal toxicity)
• Concomitant use of other soluble guanylate cyclase stimulators 1

Special Populations:

• No dosage adjustment required for geriatric patients
• No dosage adjustment needed for patients with eGFR ≥15 mL/min/1.73m² who are not on dialysis
• Not studied in patients with eGFR <15 mL/min/1.73m² or on dialysis 1

Clinical Pearls and Caveats

• Vericiguat has limited regulatory approval at present and its place in GDMT is currently evolving 3
• It should be considered after optimizing the four cornerstone therapies for HFrEF (ACE inhibitors/ARBs/ARNI, beta-blockers, mineralocorticoid receptor antagonists, and SGLT2 inhibitors) 3
• Recent evidence from the VICTOR trial showed that in stable HFrEF patients without recent worsening, vericiguat did not significantly reduce the composite endpoint of cardiovascular death or heart failure hospitalization 4
• Pregnancy testing is required before initiating treatment in females of reproductive potential 1
• Females of reproductive potential must use effective contraception during treatment and for one month after stopping treatment 1

Conclusion

Vericiguat represents an additional therapeutic option for patients with HFrEF who remain symptomatic or have experienced recent worsening despite optimal GDMT. Its unique mechanism of action as an sGC stimulator provides a novel approach to managing heart failure, particularly in high-risk patients following hospitalization or requiring IV diuretics.