Allison G Hays1, Micaela Iantorno2, Michael Schär3, Shenghan Lai4, Matthew Czarny2, Elayne Breton2, Robert N Palmer5, Andrew Whelton2, Robert G Weiss6, Gary Gerstenblith2. 1. Department of Medicine, Johns Hopkins University, 600 N Wolfe St, Baltimore, MD. Electronic address: ahays2@jhmi.edu. 2. Department of Medicine, Johns Hopkins University, 600 N Wolfe St, Baltimore, MD. 3. Department of Radiology, Division of Magnetic Resonance Research, Johns Hopkins University, 600 N. Wolfe St, Baltimore, MD. 4. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 415 N Washington St, Baltimore, MD. 5. Takeda Pharmaceuticals, Deerfield, IL. 6. Department of Medicine, Johns Hopkins University, 600 N Wolfe St, Baltimore, MD; Department of Radiology, Division of Magnetic Resonance Research, Johns Hopkins University, 600 N. Wolfe St, Baltimore, MD.
Abstract
BACKGROUND: The xanthine oxidase (XO) system is a significant source of vascular oxidative stress, which is believed to impair endothelial function, an important contributor to atherosclerotic disease. We tested whether febuxostat, a potent XO inhibitor, improves coronary endothelial function (CEF) in patients with stable coronary artery disease (CAD) in a single-center, randomized, placebo-controlled, double-blind crossover trial. METHODS:CEF was measured using noninvasive magnetic resonance imaging (MRI) assessment of changes in 30 patients with stable CAD and baseline impaired CEF. Patients received either febuxostat or placebo for 6 weeks and then were crossed over to the alternative for an additional 6 weeks. MRI-detected changes in coronary flow and in coronary cross-sectional area from rest to isometric handgrip exercise, a known endothelial-dependent stressor, were measured at the end of each 6 week period. RESULTS:Mean serum urate levels were lower at the end of the 6-week febuxostat period (2.9±0.8mg/dL) than at the end of the 6-week placebo period (5.9±0.04, P<.001). However, there were no significant differences in any of the CEF parameters measured at the end of the febuxostat and placebo periods. CONCLUSIONS: In summary, although XO inhibition with febuxostat was well tolerated and lowered serum urate, it did not improve the primary end point of the study, CEF measured using MRI after 6 weeks of treatment. In conclusion, these findings suggest that short-term inhibition of XO does not significantly improve impaired CEF in patients with stable CAD.
RCT Entities:
BACKGROUND: The xanthine oxidase (XO) system is a significant source of vascular oxidative stress, which is believed to impair endothelial function, an important contributor to atherosclerotic disease. We tested whether febuxostat, a potent XO inhibitor, improves coronary endothelial function (CEF) in patients with stable coronary artery disease (CAD) in a single-center, randomized, placebo-controlled, double-blind crossover trial. METHODS: CEF was measured using noninvasive magnetic resonance imaging (MRI) assessment of changes in 30 patients with stable CAD and baseline impaired CEF. Patients received either febuxostat or placebo for 6 weeks and then were crossed over to the alternative for an additional 6 weeks. MRI-detected changes in coronary flow and in coronary cross-sectional area from rest to isometric handgrip exercise, a known endothelial-dependent stressor, were measured at the end of each 6 week period. RESULTS: Mean serum urate levels were lower at the end of the 6-week febuxostat period (2.9±0.8mg/dL) than at the end of the 6-week placebo period (5.9±0.04, P<.001). However, there were no significant differences in any of the CEF parameters measured at the end of the febuxostat and placebo periods. CONCLUSIONS: In summary, although XO inhibition with febuxostat was well tolerated and lowered serum urate, it did not improve the primary end point of the study, CEF measured using MRI after 6 weeks of treatment. In conclusion, these findings suggest that short-term inhibition of XO does not significantly improve impaired CEF in patients with stable CAD.
Authors: Benjamin De Becker; Emeline Hupkens; Laurence Dewachter; Catherine Coremans; Cédric Delporte; Pierre van Antwerpen; Thierry Franck; Karim Zouaoui Boudjeltia; Pierre Cullus; Philippe van de Borne Journal: Physiol Rep Date: 2021-09
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Authors: Anum S Minhas; Erin Goerlich; Mary C Corretti; Armin Arbab-Zadeh; Sebastian Kelle; Thorsten Leucker; Amir Lerman; Allison G Hays Journal: Front Cardiovasc Med Date: 2022-04-15