Aernoud Fiolet

80 Chapter 3 ONGOING AND PLANNED PROSPECTIVE STUDIES ON COLCHICINE IN CORONARY ARTERY DISEASE Currently, five Phase III clinical trials examining the effect of low-dose colchicine in patients with coronary artery disease are planned or already recruiting (Table II). Two of the three already commenced trials are recruiting patients soon after an acute coronary syndrome: the COLCOT (Colchicine Cardiovascular Outcomes Trial) from Canada, and the COACS (Colchicine for Acute Coronary Syndromes) from Italy. 39,40 The LoDoCo2 trial from Australia and the Netherlands investigates colchicine 0.5 mg in patients who have been stable for at least 6 months before enrollment. 41 It is recruiting patients without reference to any baseline measure of inflammation. The study uses a 30-day trial of open-label, run-in phase for colchicine. The primary end point includes cardiovascular death, myocardial infarction, ischemic stroke, and unstable angina requiring revascularization. Its cohort reflects a heterogeneous group of patients with coronary artery disease aged 45–82 years who are receiving optimal medical treatment. All trials hope to be able to report in 2020, depending on actual event accrual. Two Phase III trials of colchicine in patients with atherosclerosis are in the final stages of planning and will likely begin recruitment this year. The CLEAR- SYNERGY (OASIS-9; Colchicine and Spironolactone in Patients With STEMI/ SYNERGY Stent Registry) study is using a 2 × 2 factorial design to investigate the effect of colchicine 1 mg/d versus spironolactone or placebo in 4000 patients who have had a recent ST-segment elevation myocardial infarction. 42 The CONVINCE (Colchicine for Prevention of Vascular Inflammation in Non-cardio Embolic Stroke) trial will investigate the effect of colchicine 0.5 mg daily on cardiovascular outcomes in ~2500 patients with previous symptomatic cerebrovascular disease. 43 The primary end point in both trials only includes cardiovascular death, myocardial infarction, and stroke, and they will likely be reported in 2022. META-ANALYSES ON COLCHICINE AND CARDIOVASCULAR OUTCOMES Two meta-analyses have examined the cardiovascular effects of colchicine in a range of prospective clinical studies (Table III). The meta-analysis conducted by the Cochrane group examined cardiovascular outcomes and colchicine use in 4992 patients from 39 randomized controlled trials from a broader range of patients with and without cardiovascular disease. 44 Overall, colchicine was found to have no