Madrid, Spain – 30 August 2025: Vericiguat reduced the risk of cardiovascular mortality, heart failure (HF) hospitalisations and all-cause mortality across a broad range of patients with HF and reduced ejection fraction (HFrEF), according to a pooled analysis presented in a Hot Line session today at ESC Congress 2025.1
The soluble guanylate cyclase stimulator, vericiguat, is approved for the treatment of worsening HF in patients with HFrEF, based on results from the VICTORIA trial published in 2020.2 Subsequently, the VICTOR trial was performed in ambulatory HFrEF patients without recent HF hospitalisation who received more contemporary background HF therapy. Results from VICTOR were presented in the same Hot Line session today.3
Presenter of the pooled analysis, Professor Javed Butler from the Baylor Scott and White Research Institute, Dallas, USA, explained: “We combined data from more than 11,000 participants in the two trials − the high-risk patients with recent worsening from VICTORIA and the lower-risk patients without recent worsening from VICTOR − to assess the effects of vericiguat on outcomes across a broad spectrum of HFrEF.”
The prespecified analysis combined patient-level data from the randomised, double-blind, placebo-controlled, international VICTORIA and VICTOR trials.2,3 Participants in VICTORIA were adults with left ventricular ejection fraction (LVEF) <45%, New York Heart Association (NYHA) functional class II−IV symptoms, elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) and estimated glomerular filtration rate (eGFR) ≥15 ml/min/1.73 m2. Participants in VICTOR were adults with LVEF ≤40%, NYHA class II−IV symptoms, elevated NT-proBNP but not >6,000 pg/ml and eGFR ≥15 ml/min/1.73 m2. Participants in both trials were randomised 1:1 to vericiguat (starting dose of 2.5 mg titrated to a 10-mg target dose) or to matching placebo.
Efficacy endpoints of the pooled analysis included a composite of cardiovascular mortality or HF hospitalisation, each of its components and all-cause mortality. In addition to the entire pooled population, endpoints were assessed in subgroups of patients with a baseline level of NT-proBNP ≤6,000 pg/ml as greater benefit was observed in VICTORIA in patients with NT-proBNP values <6,000 pg/ml.4
The 11,155 patients in the pooled analysis had a mean age of 67.2 years and 23.7% were female. A total of 88.7% of patients with measurements at baseline had an NT-proBNP <6,000 pg/ml.
In the pooled population, vericiguat significantly reduced the composite endpoint of cardiovascular mortality or HF hospitalisation vs. placebo (hazard ratio [HR] 0.91; 95% confidence interval [CI] 0.85 to 0.98; p=0.009) with similar reductions in cardiovascular 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).
Importantly, the beneficial effects of vericiguat on the primary endpoint were more pronounced in the 88.7% of participants with a baseline NT-proBNP of ≤6,000 pg/ml (HR 0.86; 95% CI 0.79 to 0.84; p=0.012). Interaction testing of treatment effect by trial indicated consistency of vericiguat effects across both trials.
Professor 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.”
ENDS
Notes to editor
This press release accompanies a presentation at ESC Congress 2025.
It does not necessarily reflect the opinion of the European Society of Cardiology.
Funding: The study was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and Bayer AG.
Disclosures: Professor Butler has received consulting fees from Abbott, American Regent, Amgen, Applied Therapeutic, AskBio, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardiac Dimension, Cardiocell, Cardior, Cardiorem, CSL Bearing, CVRx, Cytokinetics, Daxor, Edwards, Element Science, Faraday, Foundry, G3P, Innolife, Impulse Dynamics, Imbria, Inventiva, Ionis, Lexicon, Lilly, LivaNova, Janssen, Medtronic, Merck, Occlutech, Owkin, Novartis, Novo Nordisk, Pfizer, Pharmacosmos, Pharmain, Prolaio, Regeneron, Renibus, Roche, Salamandra, Sanofi, SC Pharma, Secretome, Sequana, SQ Innovation, Tenex, Tricog, Ultromics, Vifor and Zoll; and payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Novartis, Boehringer Ingelheim-Lilly, AstraZeneca, Impulse Dynamics and Vifor.
References and notes:
1‘VICTOR: Vericiguat Global Study in Participants with Chronic Heart Failure and VICTORIA: Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction’ presented during HOT LINE 2 on 30 August 2025 at 08:43 to 08:53 in Madrid (Main Auditorium).
2Armstrong PW, Pieske B, Anstrom KJ, et al. Vericiguat in patients with heart failure and reduced ejection fraction. N Engl J Med. 2020;382:1883–1893.
3‘VICTOR: Vericiguat Global Study in Participants with Chronic Heart Failure’ presented during HOT LINE 2 on 30 August 2025 at 08:33 to 08:43 in Madrid (Main Auditorium).
4Ezekowitz JA, O'Connor CM, Troughton RW, et al. N-terminal pro-B-type natriuretic peptide and clinical outcomes: Vericiguat Heart Failure with Reduced Ejection Fraction Study. JACC Heart Fail 2020;8: 931–939.
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