Journal article
The Effect of Vericiguat on Endothelial Function in Patients with Heart Failure with Reduced Ejection Fraction: A Pilot Randomized Study
The American journal of cardiology, Vol.266, pp.104-111
05/01/2026
DOI: 10.1016/j.amjcard.2026.02.062
PMID: 41765262
Abstract
Vericiguat is a soluble guanylate cyclase (sGC) stimulator previously shown to improve cardiovascular outcomes in patients with heart failure with reduced ejection fraction (HFrEF). However, the underlying mechanisms remain incompletely understood.
To evaluate the feasibility of assessing the effects of vericiguat on endothelial function.
We conducted a pilot, randomized, double-blind, placebo-controlled trial of vericiguat in HFrEF. Feasibility and efficacy outcomes were assessed at baseline and at 12 weeks on treatment. The primary efficacy outcome was brachial artery flow-mediated vasodilation (FMD). Secondary efficacy outcomes included N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP), inflammatory markers, functional capacity, and health-related quality of life (hrQOL). An ANCOVA model was used for continuous and Mantel-Haenszel tests for discretized outcomes.
We enrolled 26 participants (median age 67 years, 84% male), with 25 completing 12-week follow-up, 13 in the active and 12 in the control arm. Feasibility objectives were successfully met, including enrollment, retention, drug titration, and completeness of data collection for all endpoints. In exploratory analyses treatment with vericiguat resulted in FMD mean difference of 0.7%, [95% confidence interval (CI): -1.1%-2.5%, p=0.40], and a nominally significant reduction of log NTproBNP of -0.4 (95% CI: -0.81, -0.04, p=0.03). No significant differences in inflammatory biomarkers, functional capacity or hrQOL were observed.
We demonstrated the feasibility of assessing endothelial function in patients with HFrEF treated with vericiguat. While the pilot study size did not provide sufficient precision to confirm a treatment effect, our findings support future larger and longer studies to evaluate the therapeutic potential of sGC stimulation on endothelial function in HFrEF. (ClinicalTrials.gov number, NCT05420012).
Details
- Title: Subtitle
- The Effect of Vericiguat on Endothelial Function in Patients with Heart Failure with Reduced Ejection Fraction: A Pilot Randomized Study
- Creators
- Konstantinos Sideris - University of UtahKanokwan Bunsawat - University of UtahLina Brinker - University of UtahEmma Braun - University of UtahJarred Iacovelli - University of UtahArthur Chen - University of UtahJonah M Simmons - University of UtahJia Zhao - University of UtahSpencer Carter - University of UtahEleni Tseliou - University of UtahChristos P Kyriakopoulos - University of UtahThomas C Hanff - University of UtahRoberta Florido - University of UtahAlison M Brann - University of UtahJames C Fang - University of UtahTom Greene - University of UtahD Walter Wray - University of UtahJosef Stehlik - University of Utah
- Resource Type
- Journal article
- Publication Details
- The American journal of cardiology, Vol.266, pp.104-111
- DOI
- 10.1016/j.amjcard.2026.02.062
- PMID
- 41765262
- NLM abbreviation
- Am J Cardiol
- ISSN
- 0002-9149
- eISSN
- 1879-1913
- Publisher
- Elsevier
- Grant note
- Merck Investigator Study Program (MISP): 100000
Merck Investigator Study Program (MISP# 100000: PI: Josef Stehlik) .
- Language
- English
- Electronic publication date
- 02/27/2026
- Date published
- 05/01/2026
- Academic Unit
- Health, Sport, and Human Physiology
- Record Identifier
- 9985141955802771
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