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 - Funding Information:
Amber van Broekhoven, Niekbachsh Mohammadnia, Max J.M. Silvis, Jonathan Los, Aernoud T. L. Fiolet, Tjerk S. J. Opstal, Stefan M. Nidorf, Charley A. Budgeon, Elizabeth Byrnes, Jan G. P. Tijssen, Dominique P. V. de Kleijn, and Saloua El Messaoudi have nothing to disclose. Arend Mosterd reports membership of advisory boards and/or consultancy for AstraZeneca, Bayer, Boehringer Ingelheim, and Novartis. He will not accept personal fees; these fees will be donated to research in The Netherlands. John W. Eikelboom reports consulting/honoraria support from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi-Sankyo, Eli Lilly, GlaxoSmithKline, Pfizer, Janssen, Sanofi-Aventis, and Servier, and grants and/or in-kind support from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, GlaxoSmithKline, Pfizer, Janssen, and Sanofi-Aventis. Willem A. Bax reports membership of advisory boards and/or honoraria from Amgen, AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, NovoNordisk, and Sanofi-Aventis. Jan H. Cornel reports membership of advisory boards with Amgen and AstraZeneca. Peter L. Thompson reports grants, travel support, and honoraria from Amarin, Amgen, AstraZeneca, Bristol Myers Squibb, Merck, and Pfizer.
Funding Information:
This work was supported by the National Health Medical Research Council of Australia; a Grant from the Sir Charles Gairdner Research Advisory Committee; the Withering Foundation, The Netherlands; the Netherlands Heart Foundation; the Netherlands Organization for Health Research and Development; and a consortium of Teva, Disphar, and Tiofarma in The Netherlands.
Publisher Copyright:
© 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 - 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
AN - SCOPUS:85139709537
SN - 1173-2563
VL - 42
SP - 977
EP - 985
JO - Clinical Drug Investigation
JF - Clinical Drug Investigation
IS - 11
ER -