Abstract
The Effect Of Vericiguat On Peripheral Vascular Function In Patients With Heart Failure With Reduced Ejection Fraction: A Pilot Randomized Study
Journal of cardiac failure, Vol.32(1), p.351
01/2026
DOI: 10.1016/j.cardfail.2025.11.441
Abstract
Background
Vericiguat is a novel oral soluble guanylate cyclase stimulator previously shown to improve cardiovascular (CV) outcomes in patients with heart failure with reduced ejection fraction (HFrEF). The mechanisms underlying vericiguat’s CV benefits may include improvement in vascular function. We tested the hypothesis that short-term treatment with vericiguat would improve peripheral vascular function in patients with HFrEF.
Methods
We conducted a pilot randomized, double-blind, placebo-controlled trial in patients with HFrEF (New York Heart Association Class II-III) who received either vericiguat (target dose 10 mg daily) or placebo (in addition to HFrEF guideline-directed medical therapy). Outcomes were assessed at baseline and at 12 weeks on treatment. The primary outcome was change in brachial artery flow-mediated vasodilation (FMD, a validated noninvasive test of endothelial function that examines vascular response to increased blood flow). Secondary outcomes were change in N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP), inflammatory markers [high sensitivity C-reactive protein (hsCRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-18 (IL-18)], physical function [6-minute walk test (6MWT)], and quality of life [Kansas City Cardiomyopathy Questionnaire 12 (KCCQ-12) and visual analogue scale (VAS)]. An ANCOVA model was used for continuous outcomes and Mantel-Haenszel tests for discretized outcomes.
Results
We enrolled 25 patients, 13 randomized to vericiguat and 12 to placebo (Table). Patients receiving vericiguat reached a median daily dose of 10 mg. Mean FMD increased from 3.6% to 4.2% with vericiguat but decreased from 3.7% to 3.6% with placebo [estimated difference: 0.7%, 95% confidence interval (CI): -1.1, 2.5, p=0.4] (Figure). Mean NT-proBNP decreased from 1306 to 1231 pg/mL with vericiguat and increased from 623 to 659 pg/mL with placebo (log NT-proBNP difference: -0.4 pg/mL, 95% CI: -0.81, -0.04, p=0.03). Mean hsCRP decreased from 2.9 to 2.3 mg/L with vericiguat and increased from 2.9 to 4.2 mg/L with placebo (estimated difference: -0.6 mg/L, 95% CI: -1.4, 0.18, p=0.12). There were no significant between-group differences in the change in TNF-α, IL-6 or IL-18 levels, 6MWT distance, or KCCQ-12 or VAS scores.
Conclusions
In this pilot clinical trial we demonstrated the potential of short-term vericiguat treatment to improve peripheral vascular function in HFrEF. While the between-group difference in FMD difference did not reach statistical significance, this hypothesis generating data support further investigation into long term effects of soluble guanylate cyclase stimulation on restoring peripheral vascular function in patients with HFrEF.
Details
- Title: Subtitle
- The Effect Of Vericiguat On Peripheral Vascular Function In Patients With Heart Failure With Reduced Ejection Fraction: A Pilot Randomized Study
- Creators
- Lina Brinker - University of UtahKanokwan Bunsawat - University of UtahKonstantinos Sideris - University of UtahEmma Braun - University of UtahJarred Iacovelli - University of UtahArthur Chen - University of UtahJonah Simmons - University of UtahSpencer Carter - University of UtahEleni Tseliou - University of UtahChristos Kyriakopoulos - University of UtahThomas Hanff - University of UtahRoberta Florido - University of UtahAlison Brann - University of UtahJames Fang - University of UtahTom Greene - University of UtahWalter Wray - University of UtahJosef Stehlik - University of Utah
- Resource Type
- Abstract
- Publication Details
- Journal of cardiac failure, Vol.32(1), p.351
- DOI
- 10.1016/j.cardfail.2025.11.441
- ISSN
- 1071-9164
- Publisher
- Elseiver
- Language
- English
- Date published
- 01/2026
- Academic Unit
- Health, Sport, and Human Physiology
- Record Identifier
- 9985123943002771
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