Masato Kajikawa1, Yukihito Higashi2, Hirofumi Tomiyama3, Tatsuya Maruhashi4, Satoshi Kurisu4, Yasuki Kihara4, Akiko Mutoh5, Shin-Ichiro Ueda6. 1. Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan. 2. Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan; Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan. Electronic address: yhigashi@hiroshima-u.ac.jp. 3. Department of Cardiology, Tokyo Medical University, Tokyo, Japan. 4. Department of Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan. 5. Department of Clinical Pharmacology and Therapeutics, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan. 6. Department of Clinical Pharmacology and Therapeutics, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan. Electronic address: blessyou@med.u-ryukyu.ac.jp.
Abstract
BACKGROUND: Inflammation is associated with endothelial dysfunction and plays an important role in the pathogenesis and development of cardiovascular diseases. It has been shown that colchicine, an anti-inflammatory drug, improves the cardiovascular outcome in patients with cardiovascular disease. The purpose of this study was to evaluate the short-term effect of low-dose colchicine on endothelial function in patients with coronary artery disease (CAD). METHODS: This was a double-blind, randomized, placebo-controlled, crossover-within-subject clinical trial. A total of 28 patients with CAD received low-dose colchicine (0.5 mg/day) or a placebo for 7 days with a washout period of at least 14 days. Flow-mediated vasodilation (FMD) and serum concentrations of high-sensitivity C-reactive protein (hs-CRP) were measured after the 7-day treatment with colchicine or the placebo. RESULTS: The serum concentration of hs-CRP was significantly decreased after administration of colchicine compared with that after administration of the placebo [median (interquartile range): 0.04 (0.02-0.08) mg/dL vs. 0.07 (0.04-0.11) mg/dL, P = 0.003], while there was no significant difference in FMD between the treatments [median (interquartile range): 3.1% (1.5-5.3%) vs. 3.3% (1.9-5.2%), P = 0.384]. Colchicine, however, significantly improved FMD in coronary artery disease patients with white blood cell (WBC) counts of ≥7500 WBC/mm3 [median (interquartile range): 3.3% (2.1-6.6%) vs. 2.0% (1.4-3.8%), P = 0.043]. CONCLUSIONS: Administration of low-dose colchicine did not improve endothelial function in patients with CAD, but exploratory analysis suggested that endothelial function is significantly improved in patients with leukocyte activation.
RCT Entities:
BACKGROUND: Inflammation is associated with endothelial dysfunction and plays an important role in the pathogenesis and development of cardiovascular diseases. It has been shown that colchicine, an anti-inflammatory drug, improves the cardiovascular outcome in patients with cardiovascular disease. The purpose of this study was to evaluate the short-term effect of low-dose colchicine on endothelial function in patients with coronary artery disease (CAD). METHODS: This was a double-blind, randomized, placebo-controlled, crossover-within-subject clinical trial. A total of 28 patients with CAD received low-dose colchicine (0.5 mg/day) or a placebo for 7 days with a washout period of at least 14 days. Flow-mediated vasodilation (FMD) and serum concentrations of high-sensitivity C-reactive protein (hs-CRP) were measured after the 7-day treatment with colchicine or the placebo. RESULTS: The serum concentration of hs-CRP was significantly decreased after administration of colchicine compared with that after administration of the placebo [median (interquartile range): 0.04 (0.02-0.08) mg/dL vs. 0.07 (0.04-0.11) mg/dL, P = 0.003], while there was no significant difference in FMD between the treatments [median (interquartile range): 3.1% (1.5-5.3%) vs. 3.3% (1.9-5.2%), P = 0.384]. Colchicine, however, significantly improved FMD in coronary artery diseasepatients with white blood cell (WBC) counts of ≥7500 WBC/mm3 [median (interquartile range): 3.3% (2.1-6.6%) vs. 2.0% (1.4-3.8%), P = 0.043]. CONCLUSIONS: Administration of low-dose colchicine did not improve endothelial function in patients with CAD, but exploratory analysis suggested that endothelial function is significantly improved in patients with leukocyte activation.
Authors: Andrew P Demidowich; Anna Wolska; Sierra R Wilson; Jordan A Levine; Alexander V Sorokin; Sheila M Brady; Alan T Remaley; Jack A Yanovski Journal: J Clin Lipidol Date: 2019-10-22 Impact factor: 4.766