Mortality benefit and lifetime survival gains with vericiguat in HFrEF: Bayesian and actuarial analyses of the VICTOR trial
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.
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BibTeX
@article{fioretti2026mortality,
title = {{Mortality benefit and lifetime survival gains with vericiguat in HFrEF: Bayesian and actuarial analyses of the VICTOR trial}},
author = {Francesco Fioretti and Faiez Zannad and Derek Cyr and Kevin J Anstrom and Irina Barash and Marc P Bonaca and Stefano Corda and Anique Ducharme and Justin Ezekowitz and Anuradha Lala and Carolyn S P Lam and Eldrin F Lewis and Joann Lindenfeld and Ciaran J Mcmullan and Robert J Mentz and Marco Metra and Alanna A Morris and Christopher O’connor and Piotr Ponikowski and Yogesh N V Reddy and Giuseppe Rosano and Clara Saldarriaga and Michele Senni and James Udelson and Adriaan A Voors and Javed Butler},
journal = {European Journal of Heart Failure},
year = {2026},
month = sep,
doi = {10.1093/ejhf/xuag267},
url = {https://hal.univ-lorraine.fr/hal-05753386v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Mortality benefit and lifetime survival gains with vericiguat in HFrEF: Bayesian and actuarial analyses of the VICTOR trial
AU - Francesco Fioretti
AU - Faiez Zannad
AU - Derek Cyr
AU - Kevin J Anstrom
AU - Irina Barash
AU - Marc P Bonaca
AU - Stefano Corda
AU - Anique Ducharme
AU - Justin Ezekowitz
AU - Anuradha Lala
AU - Carolyn S P Lam
AU - Eldrin F Lewis
AU - Joann Lindenfeld
AU - Ciaran J Mcmullan
AU - Robert J Mentz
AU - Marco Metra
AU - Alanna A Morris
AU - Christopher O’connor
AU - Piotr Ponikowski
AU - Yogesh N V Reddy
AU - Giuseppe Rosano
AU - Clara Saldarriaga
AU - Michele Senni
AU - James Udelson
AU - Adriaan A Voors
AU - Javed Butler
PY - 2026
DA - 2026/09/16
JO - European Journal of Heart Failure
DO - 10.1093/ejhf/xuag267
UR - https://hal.univ-lorraine.fr/hal-05753386v1
AB - 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.
SN - 1388-9842
ER -