European journal of heart failure · 2026
Mortality benefit and lifetime survival gains with vericiguat in HFrEF: Bayesian and actuarial analyses of the VICTOR trial.
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Fioretti Francesco, Zannad Faiez, Cyr Derek, Anstrom Kevin J, Barash Irina, Bonaca Marc P, Corda Stefano, Ducharme Anique, Ezekowitz Justin, Lala Anuradha, Lam Carolyn S P, Lewis Eldrin F, Lindenfeld JoAnn, McMullan Ciaran J, Mentz Robert J, Metra Marco, Morris Alanna A, O'Connor Christopher M, Ponikowski Piotr, Reddy Yogesh N V, Rosano Giuseppe, Saldarriaga Clara, Senni Michele, Udelson James, Voors Adriaan A, Butler Javed, VICTOR Study Group
Аннотация
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.
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.