Hot Line 2: VICTOR plus VICTOR and VICTORIA
31 Aug 2025
Hot Line ESC Congress 2025 Vericiguat in patients without recent worsening and across a broad spectrum of HFrEF
“Given the positive results from the VICTORIA trial in patients with heart failure with reduced ejection fraction (HFrEF) and a recent worsening event,1 the VICTOR trial was designed to evaluate vericiguat in HFrEF patients without recent worsening who received more contemporary background therapy,” commented Professor Faiez Zannad (Université de Lorraine - Vandoeuvre-Les-Nancy, France).
In the double-blind phase III trial, patients from more than 40 countries were enrolled if they had LVEF ≤40%, NYHA class II–IV symptoms on guideline-directed medical therapy and no recent HF hospitalisation within 6 months or outpatient IV diuretic use within 3 months. 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 were randomised to vericiguat (starting dose of 2.5 mg titrated to a 10-mg target dose) or to matching placebo.
The 6,105 randomised patients had a mean age of 67 years and 23.6% were female, with almost half (47.5%) having not had prior hospitalisation for HF.
Over 18.5 months median follow-up, the primary outcome event – CV death or HF hospitalisation – occurred in 18.0% of patients with vericiguat and 19.1% with placebo (hazard ratio [HR] 0.93; 95% CI 0.83 to 1.04; p=0.22).
CV death occurred in 9.6% of patients with vericiguat and 11.3% with placebo (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 14.4% of patients with placebo (HR 0.84; 95% CI 0.74 to 0.97).
Discussing the main findings, Prof. Zannad said: “Although vericiguat did not improve the primary composite, there were fewer CV 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.”
Professor Javed Butler (Baylor Scott and White Research Institute - Dallas, USA) then presented a prespecified analysis of patient-level data from the VICTORIA and VICTOR trials.
Across 11,155 patients, vericiguat significantly reduced CV mortality or HF hospitalisation vs. placebo (HR 0.91; 95% CI 0.85 to 0.98; p=0.009).
Similar reductions were observed for CV mortality (HR 0.89; 95% CI 0.80 to 0.98; p=0.020) and HF hospitalisation (HR 0.92; 95% CI 0.84 to 1.00; p=0.043). Vericiguat was also associated with a significant reduction in all-cause mortality (HR 0.90; 95% CI 0.82 to 0.99; p=0.025). The effects of vericiguat on the primary endpoint were most pronounced in the 88.7% of participants with baseline NT-proBNP ≤6,000 pg/ml (HR 0.86; 95% CI 0.79 to 0.84; p=0.012).
Prof. Butler concluded, saying: “The cumulative evidence from pooling the VICTOR and VICTORIA trials affirms that vericiguat improved outcomes, including mortality, across the broad range of well-treated patients with HFrEF, with the clearest benefit observed in those with NT-proBNP ≤6,000 pg/ml. With once-a-day administration and a favourable safety profile, vericiguat may provide a valuable option for patients across the spectrum of HFrEF severity.”
References
- Armstrong PW, et al. N Engl J Med. 2020;382:1883–1893.
