Vericiguat did not significantly reduce the risk of cardiovascular death or heart failure hospitalisation compared to placebo in patients with chronic heart failure and reduced ejection fraction without recent worsening (HR 0.93).
RCT (n=6,105)
Double-blind
1:1
Yes
Does vericiguat reduce the composite of cardiovascular death or heart failure hospitalization in ambulatory patients with HFrEF without recent worsening?
In ambulatory patients with HFrEF without recent worsening, vericiguat did not significantly reduce the composite of cardiovascular death or heart failure hospitalization, though it was associated with a nominal reduction in cardiovascular death.
Hazard Ratio: 0.93 (95% CI 0.83–1.04)
Absolute Event Rate: 18% vs 19.1%
p-value: p=0.22
BACKGROUND Vericiguat is indicated to reduce the risk of cardiovascular death and hospitalisation for heart failure in patients with heart failure and reduced ejection fraction (HFrEF) following a recent worsening event. The aim of the VICTOR trial was to assess the effect of vericiguat in patients with HFrEF without recent heart failure worsening. METHODS In this double-blind, placebo-controlled, phase 3 trial, conducted at 482 sites across 36 countries, patients aged 18 years or older with HFrEF (left ventricular ejection fraction of ≤40%) without heart failure hospitalisation within 6 months or outpatient intravenous diuretic use within 3 months before randomisation were randomly assigned (1:1) using an intervention randomisation system with interactive response technology to oral vericiguat (target 10 mg dose) or matching placebo. The primary composite endpoint was time to cardiovascular death or heart failure hospitalisation. Efficacy endpoints were assessed in the intention-to-treat population. Adverse events were assessed in all randomly assigned patients who received at least one dose of study drug (safety population). This trial is registered with ClinicalTrials.gov, NCT05093933, and is complete. FINDINGS Between Nov 2, 2021, and Dec 21, 2023, 10 921 patients were screened and 6105 were randomly assigned: 3053 to vericiguat and 3052 to placebo. The median age was 68·0 years (IQR 61·0-75·0), 1440 (23·6%) patients were women, 4665 (76·4%) were men, 3934 (64·4%) were White, and 2899 (47·5%) had no previous hospitalisation for heart failure. During a median follow-up of 18·5 months (IQR 13·6-24·7), primary outcome events occurred in 549 (18·0%) patients in the vericiguat group and 584 (19·1%) patients in the placebo group (hazard ratio HR 0·93 95% CI 0·83-1·04; p=0·22). As prespecified in the protocol, because the primary endpoint was not statistically significant, all analyses of secondary and exploratory endpoints are considered nominal. Cardiovascular death occurred in 292 (9·6%) patients in the vericiguat group and 346 (11·3%) patients in the placebo group (HR 0·83 95% CI 0·71-0·97). Hospitalisation for heart failure occurred in 348 (11·4%) patients in the vericiguat group and in 362 (11·9%) patients in the placebo group (HR 0·95 95% CI 0·82-1·10). Serious adverse events occurred in 717 (23·5%) of 3049 patients in the vericiguat group and 751 (24·6%) of 3049 patients in the placebo group. The most common adverse event was symptomatic hypotension (345 11·3% patients in the vericiguat group and 281 9·2% in the placebo group). All-cause death occurred in 377 (12·3%) patients in the vericiguat group and 440 (14·4%) patients in the placebo group (HR 0·84 95% CI 0·74-0·97). INTERPRETATION Among patients with HFrEF and no recent worsening, vericiguat did not reduce the risk of a composite endpoint of time to cardiovascular death or heart failure hospitalisation. Fewer cardiovascular deaths were observed in the vericiguat group than in the placebo group. FUNDING Merck Sharp & Dohme (a subsidiary of Merck) and Bayer.
“When I first saw [VICTOR], I thought, 'Oh my goodness, this looks like an ICD trial,' because the only treatment I can think of that reduces death but doesn't reduce heart failure hospitalizations is an ICD.”
Butler et al. (2025) conducted an RCT in Chronic heart failure and reduced ejection fraction (HFrEF) (n=6,105). Vericiguat vs. Placebo was evaluated on Composite of time to cardiovascular death or heart failure hospitalisation (HR 0.93, 95% CI 0.83-1.04, p=0.22). Vericiguat did not significantly reduce the risk of cardiovascular death or heart failure hospitalisation compared to placebo in patients with chronic heart failure and reduced ejection fraction without recent worsening (HR 0.93).
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