What are the recommendations for implementing the Victoria Trial in clinical practice?

Recommendations for Implementing the VICTORIA Trial in Clinical Practice

Vericiguat should be prescribed for patients with heart failure with reduced ejection fraction (LVEF <45%) who have had recent heart failure worsening, defined as hospitalization within 6 months or recent IV diuretic therapy without hospitalization, and have elevated natriuretic peptides. 1

Patient Selection Criteria

• Vericiguat is indicated for patients with LVEF <45% and NYHA class II-IV symptoms who remain symptomatic despite guideline-directed medical therapy (GDMT) 1, 2
• Patients should have elevated natriuretic peptides (BNP ≥300 pg/mL or NT-proBNP ≥1000 pg/mL if in sinus rhythm; higher cutoffs with atrial fibrillation) 1, 3
• Patients must have experienced recent heart failure worsening, defined as hospitalization within 6 months or recently received IV diuretic therapy without hospitalization 1, 2

Contraindications and Precautions

• Do not use vericiguat in patients with systolic blood pressure <100 mmHg 1, 2
• Avoid use in patients with severe renal impairment (eGFR <15 mL/min/1.73 m²) 1, 3
• Do not combine with long-acting nitrates due to potential for excessive vasodilation 3
• Use with caution in patients with extremely elevated NT-proBNP levels (>5314 pg/mL), as they did not show benefit from vericiguat in the VICTORIA trial 1, 2

Dosing and Administration

• Start with 2.5 mg once daily and titrate to target dose of 10 mg once daily 1
• Monitor for symptomatic hypotension (9.1% with vericiguat vs. 7.9% with placebo) and syncope (4.0% with vericiguat vs. 3.5% with placebo) 1, 2
• Patients with baseline SBP ≥110 mmHg may experience a more pronounced initial decline in SBP over the first 16 weeks before returning to baseline levels 2, 4

Expected Clinical Benefits

• Vericiguat reduces the composite endpoint of cardiovascular death or heart failure hospitalization by 10% compared to placebo (35.5% vs. 38.5%, HR 0.90, p=0.019) 1, 2
• The number needed to treat is approximately 33 patients to prevent one primary outcome event 3
• Vericiguat also reduces the composite of any-cause death or heart failure hospitalization (HR 0.90,95% CI 0.83-0.98, p=0.02) 1, 2
• All-cause mortality showed a non-significant trend toward reduction (20.3% vs. 21.2%, HR 0.95% CI 0.84-1.07, p=0.38) 1, 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 1, 3
• The American Heart Association, American College of Cardiology, and Heart Failure Society of America give vericiguat a Class 2b recommendation for patients with HFrEF who have had a recent hospitalization or IV diuretic treatment 3
• Vericiguat represents a novel therapeutic option with a different mechanism of action from traditional heart failure medications 2

Mechanism of Action

• Vericiguat is an oral soluble guanylyl cyclase (sGC) stimulator that directly binds and stimulates sGC, increasing cyclic guanosine monophosphate (cGMP) production 1, 5
• cGMP has several beneficial effects in heart failure patients, including vasodilation, improvement in endothelial function, and decrease in fibrosis and cardiac remodeling 1, 2
• Unlike inotropic agents, vericiguat does not directly enhance myocardial contractility, making it safer for long-term use 5, 2

Clinical Pearls and Pitfalls

• The relative risk reduction of 10% in the primary outcome was lower than expected, even in a higher-risk population, so set appropriate expectations with patients 1, 2
• Vericiguat's efficacy persists regardless of baseline SBP (within the allowed range of ≥100 mmHg) 4
• The VICTORIA trial enrolled a higher-risk population than previous heart failure trials, with a median MAGGIC risk score of 23 compared to 20 in PARADIGM-HF 6
• The ongoing VICTOR trial will provide additional information on vericiguat's effects in patients with chronic HFrEF without recent worsening 7

Monitoring and Follow-up

• Monitor blood pressure regularly, especially during the initial titration phase 4
• Assess for symptomatic hypotension and syncope at follow-up visits 1, 2
• Continue to evaluate clinical response and heart failure symptoms 1
• Maintain other components of guideline-directed medical therapy alongside vericiguat 1, 3