Effect of colchicine on perioperative atrial fibrillation and myocardial injury after noncardiac surgery in patients undergoing major thoracic surgery – the COP-AF randomised controlled trial

Abstract

Background Higher levels of inflammatory biomarkers are associated with an increased risk of perioperative atrial fibrillation (AF) and myocardial injury after noncardiac surgery (MINS). Colchicine is an anti-inflammatory drug that may prevent these complications. Methods We performed an international, randomised trial at 45 sites in 11 countries. Patients aged ≥55 years and undergoing major noncardiac thoracic surgery were randomised to receive oral colchicine 0·5mg twice daily or matching placebo, starting within four hours before surgery and continuing for ten days. Healthcare providers, patients, data collectors, and adjudicators were blinded to treatment assignment. The co-primary outcomes were clinically important perioperative AF and MINS during 14 days of follow-up. This trial is registered at ClinicalTrials.gov (NCT03310125). Findings We enrolled 3209 patients between February 14, 2018, and June 27, 2023. Clinically important AF developed in 103 of 1608 (6·4%) patients assigned to colchicine, and 120 of 1601 (7·5%) patients assigned to placebo, hazard ratio (HR) 0·85 (95% confidence interval [CI] 0·65-1·10), absolute risk reduction (ARR) 1·1%, 95% CI -0·7-2·8, p=0.22. MINS occurred in 295 (18·3%) patients assigned to colchicine, and 325 (20·3%) patients assigned to placebo, HR 0·89 (95% CI 0·76-1·05), ARR 2·0%, 95% CI -0·8-4·7, p=0.16. Non-infectious diarrhoea was more common in the colchicine group, 134 (8·3%) versus 38 (2·4%) events, HR 3·64 (95% CI 2·54-5·22), but did not prolong median length of hospital stay and led to only one readmission.. Interpretation In patients undergoing major noncardiac thoracic surgery, administration of colchicine did not significantly reduce the incidence of the co-primary outcomes clinically important AF or MINS. While colchicine increased the risk of mostly benign non-infectious diarrhoea, there was an encouraging trend of fewer cardiovascular events with colchicine that requires further research.