Role of Vericiguat in Heart Failure with Reduced Ejection Fraction
Vericiguat is indicated to reduce the risk of cardiovascular death and heart failure hospitalization in adults with symptomatic chronic heart failure with ejection fraction less than 45% who have had a recent hospitalization for heart failure or need for outpatient IV diuretics. 1
Mechanism of Action and Indication
- Vericiguat is a novel, orally administered soluble guanylate cyclase (sGC) stimulator that enhances the production of cyclic guanosine monophosphate, addressing the impaired nitric oxide-sGC-cGMP pathway in heart failure patients 2
- FDA approved in January 2021 specifically for adults with symptomatic chronic heart failure with EF <45% following a hospitalization for heart failure or need for outpatient IV diuretics 1, 2
Clinical Evidence and Efficacy
- In the VICTORIA trial, vericiguat demonstrated a 10% reduction in the risk of cardiovascular death or first hospitalization for heart failure compared to placebo (HR 0.90, p=0.019) 3, 4
- The number needed to treat is approximately 33 patients to prevent one primary outcome event 3
- The benefit was greater in patients with lower N-terminal pro-brain natriuretic peptide levels and less effective in patients with a recent hospital admission 5
- In the recent VICTOR trial (2025), vericiguat did not significantly reduce the composite endpoint of cardiovascular death or heart failure hospitalization in patients without recent heart failure worsening events, though fewer cardiovascular deaths were observed in the vericiguat group 6
Place in Therapy
- Vericiguat has a Class 2b recommendation from the American Heart Association, American College of Cardiology, and Heart Failure Society of America for patients with HFrEF who have had a recent hospitalization or IV diuretic treatment 3
- It should be considered after optimizing foundational therapies, including:
- ACE inhibitors/ARBs/ARNIs
- Beta-blockers
- Mineralocorticoid receptor antagonists
- SGLT2 inhibitors 3
- Vericiguat is considered in the "other" class of medications that can be added to the four-drug class approach for HFrEF management 5
Patient Selection
- Best candidates for vericiguat therapy:
- LVEF <45% with NYHA class II-IV symptoms
- Recent heart failure worsening (hospitalization within 6 months or receipt of IV diuretics)
- Elevated natriuretic peptides (BNP ≥300 pg/mL or NT-proBNP ≥1000 pg/mL in sinus rhythm) 3
- Real-world experience suggests vericiguat might be feasible and effective even when added to quadruple therapy for heart failure 7
Contraindications and Safety Considerations
- Avoid vericiguat in patients with:
- Systolic blood pressure <100 mm Hg
- Severe renal impairment (eGFR <15 mL/min/1.73m²)
- Concomitant use with long-acting nitrates 3
- Most common adverse effects include:
- Caution is advised when initiating therapy in patients receiving dobutamine infusion due to risk of symptomatic hypotension 7
Dosing Considerations
- Target dose is 10 mg daily, with approximately 90% of patients able to tolerate this dose in clinical trials 8
- Close monitoring for hypotension is recommended, especially when initiating therapy in high-risk patients 7
Vericiguat represents an additional therapeutic option for patients with HFrEF who remain at high risk despite standard therapies, particularly following a recent decompensation event.