Key take-aways 

• The VICTOR trial investigated vericiguat in patients with ambulatory heart failure and reduced ejection fraction (HFrEF) without recent worsening who received contemporary background therapy. 
• Although vericiguat did not reduce the risk of cardiovascular mortality and HF hospitalisations, there were fewer cardiovascular deaths and all-cause deaths.  
• These results suggest vericiguat may prove beneficial in ambulatory patients with HFrEF on top of optimal background therapy.  

Madrid, Spain – 30 August 2025: Vericiguat did not reduce the risk of cardiovascular mortality and heart failure (HF) hospitalisations in ambulatory patients with HF and reduced ejection fraction (HFrEF) without recent worsening, according to late-breaking research presented in a Hot Line session today at ESC Congress 2025.¹ 

Vericiguat is an oral soluble guanylate cyclase stimulator, which restores the impaired nitric oxide signalling that is a hallmark of HFrEF. Vericiguat is approved for the treatment of worsening HF, based on a reduction in cardiovascular death or hospitalisation in the VICTORIA trial published in 2020.² 

“Given the positive results from the VICTORIA trial in patients with a recent worsening event, we designed the VICTOR trial to evaluate vericiguat in HFrEF patients without recent worsening who received more contemporary background HF therapy,” commented Professor Faiez Zannad from the Université de Lorraine, Vandoeuvre-Les-Nancy, France. 

VICTOR was a randomised, double-blind, placebo-controlled phase III trial conducted at 616 centres in 42 countries. Participants were adults with left ventricular ejection fraction (LVEF) ≤40%, New York Heart Association (NYHA) class II−IV symptoms on optimally tolerated guideline-directed medical therapy and no recent hospitalisation for HF within six months or outpatient intravenous diuretic use within three months. N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were required to be 600–6,000 pg/ml for patients in sinus rhythm and 900–6,000 pg/ml for those in atrial fibrillation. Participants with estimated glomerular filtration rate (eGFR) <15 ml/min/1.73 m2 were excluded. Participants were randomised 1:1 to vericiguat (starting dose of 2.5 mg titrated to a 10-mg target dose) or to matching placebo. The primary endpoint was a composite of cardiovascular death or hospitalisation for HF. The study was powered for cardiovascular death. 

The 6,105 randomised patients had a mean age of 67 years and 23.6% were female. In total, 47.5% of patients had no prior hospitalisation for HF and only 14% had a history of hospitalisation between 6 to 12 months prior to randomisation. Overall, 79% of participants had NYHA class II symptoms and the mean LVEF was 30%. 

Over 18.5 months median follow-up, primary outcome event – cardiovascular death or HF hospitalisation – occurred in 18.0% of patients in the vericiguat group and 19.1% of patients in the placebo group (hazard ratio [HR] 0.93; 95% confidence interval [CI] 0.83 to 1.04; p=0.22). Cardiovascular death occurred in 9.6% of patients in the vericiguat group and 11.3% of patients in the placebo group (HR 0.83; 95% CI 0.71 to 0.97), while hospitalisation for HF occurred in 11.4% and 11.9% of patients, respectively (HR 0.95; 95% CI 0.82 to 1.10). All-cause death occurred in 12.3% of patients with vericiguat and in 14.4% of patients with placebo (HR 0.84; 95% CI 0.74 to 0.97). The effects of vericiguat were consistent across prespecified subgroups. 

Serious adverse events occurred in 23.5% and 24.6% of patients in the vericiguat and placebo groups, respectively. 

Discussing the main findings, Professor Zannad said: “Although vericiguat did not improve the primary composite of cardiovascular death or hospitalisation for HF, there were fewer cardiovascular deaths with vericiguat and this translated into fewer all-cause deaths. The risk of HF hospitalisation was not reduced, which may be due, at least in part, to the high use of contemporary HF therapies and the low proportion of recent hospitalisations in this population. Overall, these findings support the use of vericiguat in ambulatory patients with HFrEF on top of contemporary therapies.” 

Results from a pooled analysis of VICTORIA and VICTOR, across the range of HF severity, will be presented in the same Hot Line session today.³  Additional results from prespecified analyses on mortality and HF hospitalisation from the VICTOR trial will be presented at ESC Congress 2025 on Monday.^4,5 

ENDS