Objective:

To assess the efficacy of vericiguat in reducing hospitalizations and cardiovascular deaths in patients with heart failure with reduced ejection fraction (HFrEF) who are already receiving foundational therapies.

Approach:

• Trial Design: The VICTOR trial is a large, event-driven study enrolling about 6,000 participants with LVEF ≤ 40% and no recent heart failure exacerbations, randomly assigned to receive either vericiguat or placebo.
• Endpoints: The primary endpoint is the time to first heart failure hospitalization (HHF) or cardiovascular death, with secondary endpoints including total HHF, cardiovascular death alone, and all-cause mortality.
• Patient Criteria: Participants had elevated NT-proBNP levels and were receiving guideline-directed therapy, with exclusions for recent heart failure events.
• Dosing and Monitoring: Vericiguat was administered starting at 2.5 mg, titrated to 10 mg, with follow-ups every 24 weeks and monitoring for adverse events.

Key Findings:

• The trial targets residual risks in stable HFrEF patients already on ARNI and SGLT2 inhibitors.
• An interim analysis is planned at 70% of expected cardiovascular deaths, with criteria for early termination based on primary and cardiovascular death endpoints.
• The study will monitor adverse events, particularly symptomatic hypotension, anemia, and liver injury.

Interpretation:

The VICTOR trial aims to assess vericiguat's efficacy in reducing cardiovascular death and rehospitalization risks in a well-treated HFrEF population.

Limitations:

• The trial excludes patients with recent heart failure events, which may limit generalizability.
• Adverse events were monitored, but specific outcomes related to vericiguat's efficacy in anemia were not detailed.

Conclusion:

The findings will help define vericiguat's utility in addressing cardiovascular death and rehospitalization risks in patients with stable, ambulatory HFrEF under quadruple therapy.

Sources:

• European Journal of Heart Failure