The VICTOR trial, formally titled the Vericiguat Global Study in Participants with Chronic Heart Failure, is one of the first, large, event-driven trials of vericiguat in a stable, ambulatory population with heart failure with reduced ejection fraction. Different from earlier studies, VICTOR enrolled patients with a left ventricular ejection fraction of ≤ 40% who did not experience recent heart failure exacerbations. This trial targeted the residual risks in patients with heart failure with reduced ejection fraction who were already receiving foundational therapies such as ARNI and SGLT2 inhibitors, to assess vericiguat’s efficacy in reducing hospitalizations and cardiovascular deaths.
In the trial, published in European Journal of Heart Failure, researchers randomly assigned about 6,000 participants 1:1 to receive either vericiguat, titrated to 10 mg, or placebo. The primary endpoint measured the time to first heart failure hospitalization (HHF) or cardiovascular death, while secondary endpoints included total HHF, cardiovascular death alone, and all-cause mortality. The event-driven trial required at least 1,080 primary endpoint events and will extend follow-up until 590 cardiovascular deaths have been recorded. Hierarchical testing will be applied to secondary endpoints if the primary endpoint achieves statistical significance.
The participants had left ventricular ejection fraction (LVEF) ≤ 40%, elevated NT-proBNP levels (600 to 6,000 pg/mL for sinus rhythm, 900 to 6,000 pg/mL for atrial fibrillation), and were receiving guideline-directed therapy. Exclusion criteria included recent heart failure events, defined as hospitalization within 6 months or intravenous diuretic treatment within 3 months. These criteria focused on a stable heart failure with reduced ejection fraction (HFrEF) population.
Vericiguat administration began at 2.5 mg, titrated up to 10 mg based on blood pressure tolerability. Adjustments occured if systolic blood pressure dropped below 90 mmHg, with temporary interruption for symptomatic hypotension. After reaching the target dose, participants continued follow-ups every 24 weeks until study completion.
The trial’s estimated event rates were based on previous HFrEF trials, projecting an HHF or cardiovascular death rate of 11.5 per 100 patient-years and cardiovascular death at 6 per 100 patient-years. An interim analysis is planned at 70% (413 events) of the expected cardiovascular deaths, with a nominal significance level of 0.005 for early termination if both primary and cardiovascular death endpoints are met.
The study monitored adverse events, particularly symptomatic hypotension, anemia, and liver injury. Mild to moderate events like headache and nausea were seen in earlier trials of vericiguat. In anticipation of high SGLT2 inhibitor use, which has shown anemia improvement in HFrEF, VICTOR was designed to evaluate vericiguat’s impact on anemia in a population with extensive baseline therapy.
VICTOR is anticipated to offer new insights into vericiguat’s role in the modern, well-treated HFrEF population. The findings may further define vericiguat’s utility in addressing cardiovascular death and rehospitalization risks in patients with stable, ambulatory HFrEF under quadruple therapy.
Conflict of interest disclosures can be found in the study.
