Key Points:
- VICTORIA and VICTOR and were randomized trials that evaluated vericiguat versus placebo in HFrEF patients with and without recent decompensation, respectively.
- This pre-specified pooled analysis of over 11,000 VICTOR and VICTORIA participants found that vericiguat reduced all-cause mortality, cardiovascular (CV) death, and heart failure (HF) hospitalizations.
- This benefit was most pronounced among those with a BNP ≤ 6000 pg/mL, a unique observation among HF drugs which warrants further research.
The VICTORIA trial found that vericiguat decreased the risk of CV death or HF hospitalization in HFrEF patients with a recent decompensation, leading to the FDA approval for vericiguat for this indication in 2021. More recently, the VICTOR trial assessed vericiguat in stable, ambulatory HFrEF patients without a recent hospitalization or need for intravenous diuresis. Although VICTOR did not meet its primary endpoint of CV death or HF hospitalization, it showed a significant reduction in CV death and worsening heart failure events, as well as reductions in sudden cardiac death, HF-related death, and all-cause death with vericiguat. This raises questions about the role of vericiguat across the full spectrum of HFrEF severity.
On August 30th 2025 the results of a pre-specified patient-level pooled analysis of the VICTOR and VICTORIA trials were presented at the European Society of Cardiology Congress in Madrid, Spain. The purpose of this analysis was to assess the overall efficacy and safety of vericiguat and explore heterogeneity of treatment effects.
Overall, 11,115 participants from VICTOR and VICTORIA were included. The mean age was 68 years, 24% were female, 65% were white, and the mean ejection fraction was 30%. About one-quarter had no prior HF hospitalization, and the majority of patients had ischemic cardiomyopathy. Background GDMT was robust across both trials.
Vericiguat was associated with a significant reduction in the risk of the primary composite of CV death or HF hospitalization (HR 0.91 [95% CI 0.85-0.98]; p= 0.009) as well as CV death (HR 0.89 [95% CI 0.80-0.98]; p= 0.02), with treatment effects emerging at approximately 4 months and 8 months, respectively. Vericiguat also significantly reduced the risk of HF hospitalization (HR 0.92 [95% CI 0.84-1.00]; p= 0.04) and all-cause death (HR 0.90 [95% CI 0.82-0.99]; p= 0.03).
There was no evidence of treatment by trial interaction. The only heterogenous treatment effect identified was for baseline NT-proBNP level: benefits appeared to be concentrated among those with baseline levels ≤ 6000 pg/mL. It should be noted that this threshold was used as an exclusion criteria in VICTOR based on a similar signal in VICTORIA. This interaction has not been observed with other HF drugs, though baseline levels were not routinely measured in older trials.
Dr. Javed Butler MD, MPH, MBA of the University and Mississippi and Baylor Scott and White Health, concluded: “Vericiguat’s benefit on clinical outcomes and favorable tolerability and safety profile offers an additional therapeutic option for the management of patients across the spectrum of HFrEF.”
