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Journal Article Randomized Controlled Trial Clinical Trial, Phase III Multicenter Study Research Support, Non-U.S. Gov't Ppublish 71 citations

PubMed: 40897189 DOI: 10.1016/S0140-6736(25)01665-4

Vericiguat in patients with chronic heart failure and reduced ejection fraction (VICTOR): a double-blind, placebo-controlled, randomised, phase 3 trial.

Lancet 406(10510):1341-1350

Authors: Javed Butler, Ciaran J McMullan, Kevin J Anstrom, Irina Barash, Marc P Bonaca, Maria Borentain, Stefano Corda, Justin A Ezekowitz, G Michael Felker, Davis Gates, Carolyn S P Lam, Eldrin F Lewis, JoAnn Lindenfeld, Robert J Mentz, Christopher M O'Connor, Piotr Ponikowski, Yogesh N V Reddy, Giuseppe M C Rosano, Clara Saldarriaga, Michele Senni, Lilin She, Pedro Pinto Teixeira, James Udelson, Alessia Urbinati, Vanja Vlajnic, Adriaan A Voors, Aiwen Xing, Mahesh J Patel, Faiez Zannad

Affiliations

  • Baylor Scott and White Research Institute, Dallas, TX, USA; University of Mississippi, Jackson, MS, USA.
  • Merck, Rahway, NJ, USA.
  • University of North Carolina, Chapel Hill, NC, USA.
  • Colorado Prevention Center Clinical Research, University of Colorado, Aurora, CO, USA.
  • Bayer Pharmaceuticals, Whippany, NJ, USA.
  • Bayer, Basel, Switzerland.
  • Canadian VIGOUR Centre, University of Alberta, Edmonton, AB, Canada.
  • Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA.
  • National Heart Centre Singapore and Duke-National University of Singapore Medical School, Singapore.
  • Stanford University School of Medicine, Stanford, CA, USA.
  • Vanderbilt University Medical Center, Nashville, TN, USA.
  • Inova Schar Heart and Vascular, Falls Church, VA, USA.
  • Wroclaw Medical University, Wroclaw, Poland.
  • Mayo Clinic, Rochester, MN, USA.
  • San Raffaele Open University of Rome, Rome, Italy and IRCCS San Raffaele, Rome, Italy.
  • CardioVID Clinic-University of Antioquia, Medellín, Colombia.
  • Papa Giovanni XXIII Hospital, Bergamo, Italy and University Bicocca, Milan, Italy.
  • Bayer, Berlin, Germany.
  • Tufts Medical Center, Boston, MA, USA.
  • University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
  • Université de Lorraine, Inserm CIC 1433, CHRU, Nancy, France.

Abstract

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.

MeSH

Heart Failure, Heart, Drug-Related Side Effects And Adverse Reactions, Heart Failure, Systolic

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