Aernoud Fiolet

236 Chapter 9 METHODS Design and population We conducted a prospective, open-label, clinical studywith pre- and post-exposure blood testing.Accordingly, adult patients with chronic coronary artery diseasewere recruited from three Dutch hospitals. Recruitment took place from May 1st, 2017 to December 4th, 2018. Patients were eligible for participation if they had coronary artery disease proven by either invasive coronary angiography or computed tomography coronary angiography with an Agatston calcium score ≥ 400 units, a high sensitivity [hs]-CRP ≥2 mg/L and if they were considered clinically stable to the discretion of the caregiver. This cut-off value for hs-CRP was chosen to select patients with a pro-inflammatory status and to optimize comparability to prior clinical studies. 7,18 Exclusion criteria were an estimated glomerular filtration rate [eGFR] < 30 ml/min/1,73m²) or a serum creatinine > 150 μmol/L, the necessity to take colchicine for any other indication or concomitant drug use of strong CYP3A4 inhibiting drugs (verapamil, azithromycine, clarithromycin). Patients had to be treated for chronic coronary artery disease without active intercurrent illnesses, frailty or a limited life expectancy according to the discretion of their treating physician. Treatment with other anti-inflammatory drugs was permitted. Obesity was defined as a body mass index of 25 kg/m² or more. Diabetes was defined by use of oral or parenteral glucose level modifying drugs. Statin intensity was categorized in accordance with the guidelines of the American College of Cardiology and American Heart Association, and high dose statin was defined as atorvastatin 40mg or 80mg dose equivalent. 19 Exposure and outcome Patients were supplied with colchicine 0.5mg once daily to be taken orally at the same time of the day. The pre-specified primary outcome of the present study was change of hs-CRP and IL-6 after 30 days of exposure to colchicine. Secondary outcomes were change in lipids, leukocyte count, thrombocyte count, red blood cell parameters, creatinine, and estimated renal function using the Chronic Kidney Disease–Epidemiology Collaboration (CKD-EPI) formula. Follow-up took place from May 1st, 2017 to February 1st, 2019. Laboratory assessment Blood samples were taken before and after 30 days of exposure to colchicine. All samples were centrifuged (1500xg at 4°C for 15 minutes) and serum was kept stored at -80°C in separate containers. Levels of CRP and IL-6 were measured in