Aernoud Fiolet

365 Clinical implications and future perspectives ACS; ACTRN: 12616000400460) aims to recruit patients with recent acute coronary syndrome with increased hsCRP and hereby determine whether baseline inflammatory status modifies the treatment effect. Results are expected in 2025. A substudy of the Colchicine and Spironolactone in Patients With Myocardial Infarction/SYNERGY Stent Registry (CLEAR SYNERGY; ClinicalTrials.gov identifiers: NCT03048825 and NCT03874338) aims to assess the effect of colchicine on neutrophil activation in response to ST-elevated myocardial infarction, and also aims to identify the clinical and genetic factors contributing to treatment response. From a clinical point of view, any new initiatives on colchicine in cardiovascular disease should include a range of patients with impaired renal function. Current evidence was collected only in patients with preserved renal clearance, with an estimated glomerular filtration rate of 35–50 ml/minute/1.73m 2 or higher. In clinical practice, however, renal impairment is not uncommon in patients with coronary disease, mainly to due to focal or generalised renal sclerosis. Although nephrologists and rheumatologists do use low-dose colchicine in patients with impaired renal function and even in those undergoing renal replacement therapy, prospective data on the use of low-dose colchicine in patientswith coronary disease and impaired renal function will help to guide the implementation of therapy in regular clinical care. Timing of commencing treatment Secondly, when implementing treatment in regular clinical care, the actual moment of commencing treatment is highly relevant. Recommendations on whether treatment should start - early after hospitalisation or during outpatient clinical follow-up - can be based on in-depth analyses of the two largest trials of colchicine, the Colchicine Cardiovascular Outcomes Trial (COLOT) and the Low- dose Colchicine 2 (LoDoCo2) trial. All patients in the COLCOT trial had prior myocardial infarction. In 40% of patients, study medication was initiated within the first week after myocardial infarction. Patients who received treatment early were generally younger, were more often smokers, and were more often taking beta-blockers. Time-to-treatment was investigated as an effect modifier for the primary and secondary end point using a stratified post hoc Cox regression analysis. Effect size was most marked in patients who initiated treatment within 3 days after myocardial infarction (hazard ratio 0.52, 95% confidence interval 0.32 to 0.84). 12 The subgroup of patients in which therapy was initiated 8 days or more after myocardial infarction was twice