Colchicine serum levels in patients with chronic coronary syndrome
J Jannink, D Joyce, C A Budgeon, J W Eikelboom, J P A Houwen, S M Nidorf, F M A C Martens, F L J Visseren, A H M de Vries Schultink, D F B Wright, A Mosterd, A T L FioletAbstract
Background
Low-dose colchicine reduces cardiovascular events in patients with chronic coronary syndrome (CCS). However, data on colchicine serum levels in this population are not available. Insight into these levels may help evaluate long-term safety and identify patient characteristics associated with higher systemic exposure.
Purpose
To quantify colchicine serum levels in patients with CCS receiving long-term low-dose colchicine and to assess the relationship with clinical characteristics and concomitant medication use.
Methods
In this cross-sectional substudy of the Low-Dose Colchicine 2 (LoDoCo2) trial, end-of-study blood samples from 885 participants treated with colchicine 0.5 mg once daily were analysed. Participants had received treatment for a median of 32.6 months (interquartile range [IQR] 24.0-48.6). Colchicine levels were measured using a liquid chromatography-mass spectrometry assay and analysed using linear regression models adjusted for age, sex, estimated glomerular filtration rate (eGFR) and statin use.
Results
The median colchicine level was 0.80 ng/mL (IQR 0.43-1.51). Overall, 95.4% of participants had colchicine levels below 3.0 ng/mL, the commonly accepted upper safe limit. Colchicine levels were 32.3% (95% confidence interval [CI] 13.9%-55.3%) higher in women compared to men. Per 10 years increase in age, colchicine levels increased 11.6% (95%CI 4.1%-20.9%). Levels were 52.2% (95%CI 22.1%-91.6%) higher in participants with an eGFR <60 ml/min/1.73m2 compared to those with an eGFR >90 ml/min/1.73m2, and 13.9% (95%CI 1.0%-27.1%) higher in those who used betablocker therapy versus those who did not. Statin use was not associated with colchicine levels.
Conclusion
In patients with CCS receiving colchicine 0.5 mg once daily for a median of 32.6 months, colchicine levels were generally within accepted safety ranges. Although higher levels were observed in women, older individuals and those with impaired renal function, there were no clinically relevant increases. Levels exceeding the upper safe limit were uncommon. These findings support the safety of long-term, low-dose colchicine in this patient population.Colchicine levels by key covariates