Aernoud Fiolet

225 Colchicine in chronic coronary disease in relation to history of acute coronary syndrome DISCUSSION Our analyses of the LoDoCo2 trial show that patients with a history of very remote ACS remain at high risk of recurrent major adverse cardiovascular events, and that the efficacy of colchicine in patients with chronic coronary disease is independent of prior ACS status, producing consistent benefits irrespective of time since the most recent ACS event. In the current era of aggressive and often complete coronary revascularization after ACS, the risk of major adverse cardiovascular events plateaus after the first six months. 13, 14 The pillars of secondary prevention include lifestyle modification, and medical therapies, including lipid, blood pressure, and glucose lowering therapies as well as anti-thrombotic therapy. 15,16 Despite the routine use of these therapies, however, patients with a history of ACS continue to experience major adverse cardiovascular events caused by plaque disruption and superimposed thrombus formation. This residual risk is at least partly explained by ongoing inflammation that is largely unaffected by currently recommended secondary prevention therapies. 17 Our results, indicating that residual risk is independent of timing of prior ACS, seem to contradict the results of the Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Patients With Elevated Risk (FOURIER) trial, which found increased risk for cardiovascular events in patients included within two years of prior myocardial infarction compared to patients with more distant prior myocardial infarction at inclusion. 18 This apparent discrepancy is likely explained by the inclusion in FOURIER of patients immediately following myocardial infarction. These patients were excluded from the LoDoCo2 trial and are at higher risk of recurrent events than patients who are at least six months after their most recent episode of ACS. Data from long-term trials of lipid lowering and anti- thrombotic therapies confirm our results, and further highlight the necessity of compliance with optimal medical therapy in patients with chronic coronary disease, even when they are presumed to be “stable”. 19,20 Subgroup analysis of the COLCOT trial has suggested that initiation of low-dose colchicine within three days after the index myocardial infarction produces greater benefits (48% risk reduction in the primary outcome) than when treatment is initiated 4 to 7 or 8 to 30 days after the event (4% and 23% relative risk reductions, respectively). 10 These additional benefits could be based on the potential of colchicine to lower reperfusion injury in the setting of acute myocardial