Physicians' Academy for Cardiovascular Education

Relationship between changes in NT-proBNP, efficacy of sGC stimulator, and clinical outcomes in HFrEF

Sequential Evaluation of NT-proBNP in Heart Failure: Insights Into Clinical Outcomes and Efficacy of Vericiguat

Literature - Armstrong PW, Zheng Y, Troughton RW, et al. - JACC Heart Fail. 2022 Sep;10(9):677-688. doi: 10.1016/j.jchf.2022.04.015

Introduction and methods


Recently, the VICTORIA (Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction) trial showed a reduction in the primary composite outcome of CV death or HF hospitalization with vericiguat—an oral soluble guanylate cyclase stimulator —in patients with recent worsening chronic HF compared with placebo [1]. A prespecified subgroup analysis suggested less benefit for patients with an NT-proBNP level in the highest quartile at randomization (>5314 pg/mL) and more benefit for those with NT-proBNP <4000 pg/mL [2]. For the high-risk population of HFrEF patients with a recent worsening event, it is important to determine whether there is a relationship between sequential changes in NT-proBNP levels, treatment with vericiguat, and clinical outcomes.

Aim of the study

The objectives of this post-hoc analysis of the VICTORIA trial were: (1) assessing the relationship between sequential changes in plasma NT-proBNP level and the primary composite outcome of CV death or HF hospitalization; (2) evaluating the effect of vericiguat compared with placebo on changes in NT-proBNP level; and (3) exploring the association between the efficacy of vericiguat and NT-proBNP changes.


In the VICTORIA trial, 5050 patients with recent worsening chronic HFrEF and elevated plasma NT-proBNP levels (>1000 pg/mL in sinus rhythm and >1600 pg/mL in AF) were randomized to vericiguat or placebo. For 4805 patients (95%), NT-proBNP measurements were available at randomization: 2414 in the vericiguat group and 2391 in the placebo group. Additional samples were taken at 16, 32, 48, and 96 weeks.

Patients were divided into 4 groups based on their NT-proBNP level at randomization (≤2816 pg/mL or >2816 pg/mL, which was the median value) and the subsequent relative NT-proBNP change between randomization and week 16 (≥20% reduction or <20% reduction, including increases).


The association of the primary composite outcome with the NT-proBNP change between randomization and week 16 was assessed. The authors chose week 16 because it was the first post-randomization NT-proBNP sample collected and it provided the optimal point at which the extent of change was greatest and loss due to missing samples, death, or other reasons was smallest. Joint modeling was used to examine how vericiguat treatment was related to (event-free) survival via NT-proBNP levels. The relationship between vericiguat, NT-proBNP levels, and clinical outcomes was assessed with mediation analysis.

Main results

Association between NT-proBNP changes at week 16 and clinical outcomes

Evolution of NT-proBNP changes according to treatment group

Relationship between evolution of NT-proBNP changes and efficacy of vericiguat


Patients with worsening HFrEF who were treated with vericiguat had greater declines and lesser increments in sequential NT-proBNP measures compared with placebo. These changes appeared to be related to a modest relative reduction in the primary composite outcome of CV death or HF hospitalization by vericiguat treatment.


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Find this article online at JACC Heart Fail.

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