The Effect of Years-Long Exposure to Low-Dose Colchicine on Renal and Liver Function and Blood Creatine Kinase Levels: Safety Insights from the Low-Dose Colchicine 2 (LoDoCo2) Trial

Clin Drug Investig. 2022 Nov;42(11):977-985. doi: 10.1007/s40261-022-01209-8. Epub 2022 Oct 8.

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.

Publication types

  • Clinical Trial

MeSH terms

  • Aged
  • Biomarkers
  • Colchicine* / adverse effects
  • Coronary Artery Disease*
  • Creatine Kinase / pharmacology
  • Creatinine
  • Female
  • Humans
  • Kidney / physiology
  • Liver
  • Male

Substances

  • Biomarkers
  • Colchicine
  • Creatine Kinase
  • Creatinine

Associated data

  • ANZCTR/ACTRN12614000093684