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Vericiguat in patients with chronic heart failure and reduced ejection fraction (VICTOR): a double-blind,
Javed Butler1, Ciaran J McMullan2, Kevin J Anstrom3
1Baylor Scott and White Research Institute, Dallas, TX, USA; University of Mississippi, Jackson, MS, USA.
Insights
Vericiguat did not significantly reduce the risk of cardiovascular death or heart failure hospitalization in patients with heart failure with reduced ejection fraction (HFrEF) without recent worsening. However, fewer cardiovascular deaths were observed in the vericiguat group.
Area of Science:
- Cardiovascular Medicine
- Clinical Pharmacology
- Heart Failure Research
Background:
- Vericiguat is approved for specific heart failure with reduced ejection fraction (HFrEF) patients post-worsening event.
- The VICTOR trial investigated vericiguat's efficacy in HFrEF patients without recent heart failure exacerbation.
Purpose of the Study:
- To evaluate the effect of vericiguat on cardiovascular death and heart failure hospitalization in HFrEF patients not recently experiencing a worsening event.
- To assess the safety and efficacy of vericiguat compared to placebo in a broader HFrEF population.
Main Methods:
- A double-blind, placebo-controlled, phase 3 trial involving 6105 patients with HFrEF (LVEF ≤40%) without recent hospitalisation or IV diuretic use.
- Patients were randomized to oral vericiguat (10 mg target dose) or placebo.
- The primary composite endpoint was the time to cardiovascular death or heart failure hospitalization.
Main Results:
- The primary composite endpoint did not reach statistical significance (HR 0.93; p=0.22).
- Fewer cardiovascular deaths occurred in the vericiguat group (9.6%) compared to placebo (11.3%) (HR 0.83).
- All-cause mortality was also lower in the vericiguat group (12.3% vs. 14.4%). Symptomatic hypotension was the most common adverse event.
Conclusions:
- Vericiguat did not demonstrate a significant reduction in the composite endpoint of cardiovascular death or heart failure hospitalization in HFrEF patients without recent worsening.
- A trend towards fewer cardiovascular deaths and lower all-cause mortality was observed with vericiguat.
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.
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