Amber van Broekhoven1, Niekbachsh Mohammadnia1, Max J M Silvis1,2, Jonathan Los1, Aernoud T L Fiolet2,3, Tjerk S J Opstal1,4, Arend Mosterd3,5, John W Eikelboom6, Stefan M Nidorf7,8, Charley A Budgeon9, Elizabeth Byrnes10, Willem A Bax11, Jan G P Tijssen12,13, Dominique P V de Kleijn14,15, Peter L Thompson7,9,16, Saloua El Messaoudi1, Jan H Cornel17,18,19. 1. Department of Cardiology, Radboud University Medical Centre, Geert Grooteplein Zuid 10, 6525GA, Nijmegen, The Netherlands. 2. Department of Cardiology, University Medical Centre Utrecht, Utrecht, The Netherlands. 3. Dutch Network for Cardiovascular Research (WCN), Utrecht, The Netherlands. 4. Department of Cardiology, Northwest Clinics, Alkmaar, The Netherlands. 5. Department of Cardiology, Meander Medical Centre, Amersfoort, The Netherlands. 6. Department of Medicine, McMaster University, Hamilton, ON, Canada. 7. Heart and Vascular Research Institute of Western Australia, Perth, WA, Australia. 8. GenesisCare Western Australia, Perth, WA, Australia. 9. School of Medicine, University of Western Australia, Perth, WA, Australia. 10. PathWest Laboratory Medicine, QEII Medical Centre, Perth, WA, Australia. 11. Department of Internal Medicine, Northwest Clinics, Alkmaar, The Netherlands. 12. Department of Cardiology, Amsterdam University Medical Centre, Amsterdam, The Netherlands. 13. Cardialysis BV, Rotterdam, The Netherlands. 14. The Netherlands Heart Institute, Utrecht, The Netherlands. 15. Department of Vascular Surgery, University Medical Centre Utrecht, Utrecht, The Netherlands. 16. Sir Charles Gairdner Hospital, Perth, WA, Australia. 17. Department of Cardiology, Radboud University Medical Centre, Geert Grooteplein Zuid 10, 6525GA, Nijmegen, The Netherlands. janhein.cornel@radboudumc.nl. 18. Dutch Network for Cardiovascular Research (WCN), Utrecht, The Netherlands. janhein.cornel@radboudumc.nl. 19. Department of Cardiology, Northwest Clinics, Alkmaar, The Netherlands. janhein.cornel@radboudumc.nl.
Abstract
BACKGROUND AND OBJECTIVE: The Low-Dose Colchicine-2 (LoDoCo2) trial showed that 2-4 years exposure to colchicine 0.5 mg once daily reduced the risk of cardiovascular events in patients with chronic coronary artery disease. The potential effect of years-long exposure to colchicine on renal or liver function and creatine kinase (CK) has not been systematically evaluated and was investigated in this LoDoCo2 substudy. METHODS: Blood samples drawn from 1776 participants at the close-out visit of the LoDoCo2 trial were used to measure markers of renal function (creatinine, blood urea nitrogen [BUN]), liver function (alanine aminotransferase [ALT], γ-glutamyl transferase [GGT], bilirubin and albumin), and CK. Renal and liver function as well as hyperCKemia (elevated CK) were categorized to the degree of elevation biomarkers as mild, mild/moderate, moderate/severe, and marked elevations. RESULTS: In total, 1776 participants (mean age 66.5 years, 72% male) contributed to this analysis, with a median exposure to trial medication of 32.7 months. Compared with placebo, colchicine was not associated with changes in creatinine and BUN but was associated with elevations in ALT (30 U/L vs. 26 U/L; p < 0.01) and CK (123 U/L vs. 110 U/L; p < 0.01). Most elevations in ALT and CK were mild in both treatment groups. There were no moderate to marked ALT elevations (> 5-10 × upper limit of normal [ULN]) in both treatment groups, and 6 (0.7%) colchicine-treated vs. 2 (0.2%) placebo-treated participants had moderate to marked CK elevations (> 5-10 × ULN). CONCLUSION: In chronic coronary artery disease, 2-4 years of exposure to colchicine 0.5 mg once daily was associated with small elevations in ALT and CK, but was not associated with changes in renal function. TRIAL REGISTRATION: https://www.anzctr.org.au ; ACTRN12614000093684, 24 January 2014.
BACKGROUND AND OBJECTIVE: The Low-Dose Colchicine-2 (LoDoCo2) trial showed that 2-4 years exposure to colchicine 0.5 mg once daily reduced the risk of cardiovascular events in patients with chronic coronary artery disease. The potential effect of years-long exposure to colchicine on renal or liver function and creatine kinase (CK) has not been systematically evaluated and was investigated in this LoDoCo2 substudy. METHODS: Blood samples drawn from 1776 participants at the close-out visit of the LoDoCo2 trial were used to measure markers of renal function (creatinine, blood urea nitrogen [BUN]), liver function (alanine aminotransferase [ALT], γ-glutamyl transferase [GGT], bilirubin and albumin), and CK. Renal and liver function as well as hyperCKemia (elevated CK) were categorized to the degree of elevation biomarkers as mild, mild/moderate, moderate/severe, and marked elevations. RESULTS: In total, 1776 participants (mean age 66.5 years, 72% male) contributed to this analysis, with a median exposure to trial medication of 32.7 months. Compared with placebo, colchicine was not associated with changes in creatinine and BUN but was associated with elevations in ALT (30 U/L vs. 26 U/L; p < 0.01) and CK (123 U/L vs. 110 U/L; p < 0.01). Most elevations in ALT and CK were mild in both treatment groups. There were no moderate to marked ALT elevations (> 5-10 × upper limit of normal [ULN]) in both treatment groups, and 6 (0.7%) colchicine-treated vs. 2 (0.2%) placebo-treated participants had moderate to marked CK elevations (> 5-10 × ULN). CONCLUSION: In chronic coronary artery disease, 2-4 years of exposure to colchicine 0.5 mg once daily was associated with small elevations in ALT and CK, but was not associated with changes in renal function. TRIAL REGISTRATION: https://www.anzctr.org.au ; ACTRN12614000093684, 24 January 2014.
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