Mortality benefit and lifetime survival gains with vericiguat in HFrEF: Bayesian and actuarial analyses of the VICTOR trial
Year: 2026
Type: article
Abstract: BACKGROUND: The VICTOR trial did not meet its primary composite endpoint of cardiovascular death or first hospitalization for heart failure (HF) but demonstrated a nominally significant reduction in the prespecified and powered endpoint of cardiovascular death with vericiguat in patients with HF and reduced ejection fraction (HFrEF). Bayesian and actuarial methods offer complementary frameworks to quantify the probability and lifetime implications of this mortality benefit. METHODS: This post hoc analysis of the VICTOR trial applied Bayesian and actuarial analyses. Bayesian analysis estimated the probability that vericiguat reduces mortality, integrating trial data with prior evidence. Actuarial analysis used restricted mean survival time (RMST) to quantify event-free survival at 1 and 2 years, and age-based Cox proportional hazards modelling to project lifetime survival gains across ages 45-80. RESULTS: Bayesian analyses showed a consistently high probability of mortality benefit with vericiguat, regardless of whether sceptical or optimistic prior evidence was weighted. For cardiovascular mortality, the sceptical prior yielded a 98.4% posterior probability of any benefit, a 77.6% probability of at least a 10% relative reduction, and a 20.4% probability of at least a 20% reduction. The VICTORIA-based optimistic prior yielded 99.1%, 60.7%, and 2.2%, respectively. Similar results were observed for all-cause mortality. Actuarial analyses demonstrated greater event-free survival with vericiguat over 1 and 2 years. Lifetime projections suggested that vericiguat may extend overall survival across a broad age range, with the largest gains observed of ∼1.6 to 1.9 years for those aged 55 to 60 at randomization. CONCLUSION: In this post hoc analysis, Bayesian and actuarial methods provided hypothesis-generating evidence of a cardiovascular mortality benefit with vericiguat in HFrEF, an endpoint for which the trial was prospectively powered, that warrants prospective confirmation.
DOI: 10.1093/ejhf/xuag267
Authors: Francesco Fioretti, Faiez Zannad, Derek Cyr, Kevin J Anstrom, Irina Barash, Marc P Bonaca, Stefano Corda, Anique Ducharme, Justin Ezekowitz, Anuradha Lala, Carolyn S P Lam, Eldrin F Lewis, JoAnn Lindenfeld, Ciaran J McMullan, Robert J Mentz, Marco Metra, Alanna A Morris, Christopher M O’Connor, Piotr Ponikowski, Yogesh N V Reddy, Giuseppe Rosano, Clara Saldarriaga, Michele Senni, James Udelson, Adriaan A Voors, Javed Butler
Institutions: Baylor Scott & White Research Institute, Inserm, Centre Hospitalier Régional et Universitaire de Nancy, Université de Lorraine, Duke University, Duke Clinical Research Institute, University of North Carolina at Chapel Hill, Merck & Co., Inc., Rahway, NJ, USA (United States), University of Colorado Anschutz, University of Colorado Denver, Bayer (Switzerland), Montreal Heart Institute, Université de Montréal, University of Alberta, Canadian VIGOUR Centre, Icahn School of Medicine at Mount Sinai, National University of Singapore, National University Heart Centre Singapore, Duke-NUS Medical School, National Heart Centre Singapore, Stanford Medicine, Stanford University, Vanderbilt University Medical Center, Vita-Salute San Raffaele University, IRCCS Ospedale San Raffaele, Emory University, Inova Health System, University of Wrocław, Wroclaw Medical University, Mayo Clinic, IRCCS San Raffaele Roma, Universidad de Antioquia, Ospedale Papa Giovanni XXIII, Tufts University, Tufts Medical Center, University Medical Center Groningen, University of Groningen, University of Mississippi
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $5,300
Funder: Bayer
OpenAlex ID: W7213400660