Aernoud Fiolet

217 Colchicine in chronic coronary disease in relation to history of acute coronary syndrome INTRODUCTION I nflammation drives all phases of atherosclerosis 1 , providing a therapeutic avenue to reduce cardiovascular complications. 2 The first anti-inflammatory drug that reduced cardiovascular events in a placebo-controlled clinical trial (Canakinumab Anti-Inflammatory Thrombosis Outcomes Study; CANTOS) was canakinumab, a therapeutic antibody targeting interleukin-1 β produced by nucleotide-binding oligomerizationdomain-, leucine-richrepeat-,andpyrindomain-containingprotein 3 (NLRP3) inflammasome activation. 3 While this trial provided proof-of-concept of the inflammation hypothesis, cardiovascular registration of canakinumab has been halted. 4 Colchicine is an inexpensive anti-inflammatory drug that is widely used to treat gout, pericarditis and familial Mediterranean fever. 5 Similar to canakinumab, colchicine attenuates NLRP3 inflammasome activation. 6 although experimental studies suggest colchicine also inhibits phagocytosis, neutrophil recruitment and function. 7 The potential for benefit suggested by preclinical and retrospective studies led to two large randomized clinical trials. 8 The Colchicine Cardiovascular Outcomes Trial (COLCOT) trial, which included 4,765 patients with a very recent history (<30 days) of myocardial infarction, demonstrated that colchicine compared with placebo reduced the risk of cardiovascular events by 23%. 9 However, the benefits appeared to be greatest in patients who started colchicine within three days of the acute event. 10 The Low- dose Colchicine 2 (LoDoCo2) trial, which included 5,522 patients with chronic coronary disease, demonstrated that colchicine compared with placebo reduced the risk of cardiovascular events by 31%, driven by reductions in both myocardial infarction and ischemia-driven coronary revascularization. However, unlike COLCOT, the LoDoCo2 trial excluded patients who had experienced an acute coronary syndrome (ACS) within six months prior to randomization. 11 The results of the COLCOT and LoDoCo2 trials raise questions about the benefit of colchicine in relation to the time of onset of treatment following a prior episode of ACS. The objective of the current study was to investigate, using the LoDoCo2 dataset, the risk for major adverse cardiovascular events based on priorACS status, in order to determine whether the effects of colchicine compared with placebo are consistent in patients with no prior, recent, remote, or very remote ACS.