TY - JOUR
T1 - The Effect of Years-Long Exposure to Low-Dose Colchicine on Renal and Liver Function and Blood Creatine Kinase Levels
T2 - Safety Insights from the Low-Dose Colchicine 2 (LoDoCo2) Trial
AU - van Broekhoven, Amber
AU - Mohammadnia, Niekbachsh
AU - Silvis, Max J M
AU - Los, Jonathan
AU - Fiolet, Aernoud T L
AU - Opstal, Tjerk S J
AU - Mosterd, Arend
AU - Eikelboom, John W
AU - Nidorf, Stefan M
AU - Budgeon, Charley A
AU - Byrnes, Elizabeth
AU - Bax, Willem A
AU - Tijssen, Jan G P
AU - de Kleijn, Dominique P V
AU - Thompson, Peter L
AU - El Messaoudi, Saloua
AU - Cornel, Jan H
N1 - © 2022. The Author(s).
PY - 2022/11
Y1 - 2022/11
N2 - 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.
AB - 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.
UR - https://www.webofscience.com/wos/woscc/full-record/WOS:000865167400001
UR - http://www.scopus.com/inward/record.url?scp=85139709537&partnerID=8YFLogxK
U2 - 10.1007/s40261-022-01209-8
DO - 10.1007/s40261-022-01209-8
M3 - Article
C2 - 36208364
SN - 1173-2563
VL - 42
SP - 977
EP - 985
JO - Clinical Drug Investigation
JF - Clinical Drug Investigation
IS - 11
ER -