Study title: Vericiguat Global Study in Participants with Chronic Heart Failure: Design of the VICTOR trial

Conferance: ESC Congress 2025, Madrid

Link:https://esc365.escardio.org/presentation/312145

Prepared by: Dr. Yunus Emre Özbebek

Introduction
Vericiguat, a soluble guanylate cyclase (sGC) stimulator, is an approved treatment for patients with HFrEF. In the VICTORIA trial, vericiguat reduced the risk of cardiovascular death or hospitalization for heart failure (HHF) in patients with recently worsened HFrEF; however, the follow-up period was relatively short (10.8 months), and the patient population represented a higher-risk cohort.

The VICTOR trial was designed to evaluate the efficacy and safety of vericiguat in more stable, compensated ambulatory patients with HFrEF, with no HF events in the past 6 months and receiving contemporary guideline-directed medical therapy (GDMT). The primary hypothesis of the study was that vericiguat would reduce the composite endpoint of cardiovascular death plus first HHF compared with placebo.

Methods
VICTOR is a phase 3, double-blind, placebo-controlled, 1:1 randomized, event-driven trial. A total of 6105 patients were enrolled from 482 centers across 36 countries.

Inclusion criteria were HFrEF (LVEF ?40%), New York Heart Association (NYHA) class II–IV, NT-proBNP between 600–6000 pg/mL (?900 pg/mL in atrial fibrillation), no hospitalization for heart failure within the previous 6 months, no intravenous diuretic use within the previous 3 months, and stable GDMT. Participants were followed for a median of 18.5 months until the occurrence of 590 cardiovascular deaths, the target number of events. Vericiguat was titrated from 2.5 mg to 10 mg once daily as tolerated.

Results
The primary endpoint was the composite of cardiovascular death or first HHF. This occurred in 18.0% of patients in the vericiguat group (549 events) and 19.1% of patients in the placebo group (584 events), which was not statistically significant (HR: 0.93; 95% CI: 0.83–1.04; p=0.22). Among secondary endpoints, cardiovascular death was significantly lower in the vericiguat group (HR: 0.83; 95% CI: 0.71–0.97; p=0.02). All-cause mortality was also significantly reduced (HR: 0.84; 95% CI: 0.74–0.97; p=0.02). Total worsening HF events (including hospitalization, urgent visits, and oral diuretic intensification) were significantly lower with vericiguat (HR: 0.90; 95% CI: 0.81–1.00; p=0.047). In addition, sudden cardiac death (HR: 0.75; 95% CI: 0.56–0.99; p=0.04) and HF-related death (HR: 0.71; 95% CI: 0.54–0.94; p=0.02) were notably reduced in the vericiguat group.

Safety
The incidence of adverse events was similar between the vericiguat and placebo groups. Symptomatic hypotension occurred in 11.3% of patients in the vericiguat group and 9.2% in the placebo group. Anemia was reported in 7.6% versus 6.3% of patients, respectively. Serious adverse events occurred in approximately 24% of patients in both groups. Treatment discontinuation due to adverse events was 8.3% in the vericiguat group and 7.2% in the placebo group.

Conclusion
Vericiguat did not significantly reduce the primary composite endpoint. However, it was associated with a significant reduction in cardiovascular death and all-cause mortality. Moreover, reductions in sudden cardiac death and HF-related death were observed. Overall, these findings support a beneficial effect of vericiguat in patients with compensated HFrEF receiving contemporary GDMT.