Background Higher levels of inflammatory biomarkers are associated with an increased risk of perioperative atrial fibrillation and myocardial injury after non-cardiac surgery (MINS). Colchicine is an anti-inflammatory drug that might reduce the incidence of these complications.Methods COP-AF was a randomised trial conducted at 45 sites in 11 countries. Patients aged 55 years or older and undergoing major non-cardiac thoracic surgery were randomly assigned (1:1) to receive oral colchicine 0 center dot 5 mg twice daily or matching placebo, starting within 4 h before surgery and continuing for 10 days. Randomisation was done with use of a computerised, web-based system, and was stratified by centre. Health-care providers, patients, data collectors, and adjudicators were masked to treatment assignment. The coprimary outcomes were clinically important perioperative atrial fibrillation and MINS during 14 days of follow-up. The main safety outcomes were a composite of sepsis or infection, and non-infectious diarrhoea. The intention-to-treat principle was used for all analyses. This trial is registered with ClinicalTrials.gov, NCT03310125.Findings Between Feb 14, 2018, and June 27, 2023, we enrolled 3209 patients (mean age 68 years [SD 7], 1656 [51 center dot 6%] male). Clinically important atrial fibrillation occurred in 103 (6 center dot 4%) of 1608 patients assigned to colchicine, and 120 (7 center dot 5%) of 1601 patients assigned to placebo (hazard ratio [HR] 0 center dot 85, 95% CI 0 center dot 65 to 1 center dot 10; absolute risk reduction [ARR] 1 center dot 1%, 95% CI -0 center dot 7 to 2 center dot 8; p=0 center dot 22). MINS occurred in 295 (18 center dot 3%) patients assigned to colchicine and 325 (20 center dot 3%) patients assigned to placebo (HR 0 center dot 89, 0 center dot 76 to 1 center dot 05; ARR 2 center dot 0%, -0 center dot 8 to 4 center dot 7; p=0 center dot 16). The composite outcome of sepsis or infection occurred in 103 (6 center dot 4%) patients in the colchicine group and 83 (5 center dot 2%) patients in the placebo group (HR 1 center dot 24, 0 center dot 93-1 center dot 66). Non-infectious diarrhoea was more common in the colchicine group (134 [8 center dot 3%] events) than the placebo group (38 [2 center dot 4%]; HR 3 center dot 64, 2 center dot 54-5 center dot 22).Interpretation In patients undergoing major non-cardiac thoracic surgery, administration of colchicine did not significantly reduce the incidence of clinically important atrial fibrillation or MINS but increased the risk of mostly benign non-infectious diarrhoea.Funding Canadian Institutes of Health Research, Accelerating Clinical Trials Consortium, Innovation Fund of the Alternative Funding Plan for the Academic Health Sciences Centres of Ontario, Population Health Research Institute, Hamilton Health Sciences, Division of Cardiology at McMaster University, Canada; Hanela Foundation, Switzerland; and General Research Fund, Research Grants Council, Hong Kong.Copyright (c) 2023 Elsevier Ltd. All rights reserved.

Effect of colchicine on perioperative atrial fibrillation and myocardial injury after non-cardiac surgery in patients undergoing major thoracic surgery (COP-AF): an international randomised trial

Marcucci, Maura;
2023-01-01

Abstract

Background Higher levels of inflammatory biomarkers are associated with an increased risk of perioperative atrial fibrillation and myocardial injury after non-cardiac surgery (MINS). Colchicine is an anti-inflammatory drug that might reduce the incidence of these complications.Methods COP-AF was a randomised trial conducted at 45 sites in 11 countries. Patients aged 55 years or older and undergoing major non-cardiac thoracic surgery were randomly assigned (1:1) to receive oral colchicine 0 center dot 5 mg twice daily or matching placebo, starting within 4 h before surgery and continuing for 10 days. Randomisation was done with use of a computerised, web-based system, and was stratified by centre. Health-care providers, patients, data collectors, and adjudicators were masked to treatment assignment. The coprimary outcomes were clinically important perioperative atrial fibrillation and MINS during 14 days of follow-up. The main safety outcomes were a composite of sepsis or infection, and non-infectious diarrhoea. The intention-to-treat principle was used for all analyses. This trial is registered with ClinicalTrials.gov, NCT03310125.Findings Between Feb 14, 2018, and June 27, 2023, we enrolled 3209 patients (mean age 68 years [SD 7], 1656 [51 center dot 6%] male). Clinically important atrial fibrillation occurred in 103 (6 center dot 4%) of 1608 patients assigned to colchicine, and 120 (7 center dot 5%) of 1601 patients assigned to placebo (hazard ratio [HR] 0 center dot 85, 95% CI 0 center dot 65 to 1 center dot 10; absolute risk reduction [ARR] 1 center dot 1%, 95% CI -0 center dot 7 to 2 center dot 8; p=0 center dot 22). MINS occurred in 295 (18 center dot 3%) patients assigned to colchicine and 325 (20 center dot 3%) patients assigned to placebo (HR 0 center dot 89, 0 center dot 76 to 1 center dot 05; ARR 2 center dot 0%, -0 center dot 8 to 4 center dot 7; p=0 center dot 16). The composite outcome of sepsis or infection occurred in 103 (6 center dot 4%) patients in the colchicine group and 83 (5 center dot 2%) patients in the placebo group (HR 1 center dot 24, 0 center dot 93-1 center dot 66). Non-infectious diarrhoea was more common in the colchicine group (134 [8 center dot 3%] events) than the placebo group (38 [2 center dot 4%]; HR 3 center dot 64, 2 center dot 54-5 center dot 22).Interpretation In patients undergoing major non-cardiac thoracic surgery, administration of colchicine did not significantly reduce the incidence of clinically important atrial fibrillation or MINS but increased the risk of mostly benign non-infectious diarrhoea.Funding Canadian Institutes of Health Research, Accelerating Clinical Trials Consortium, Innovation Fund of the Alternative Funding Plan for the Academic Health Sciences Centres of Ontario, Population Health Research Institute, Hamilton Health Sciences, Division of Cardiology at McMaster University, Canada; Hanela Foundation, Switzerland; and General Research Fund, Research Grants Council, Hong Kong.Copyright (c) 2023 Elsevier Ltd. All rights reserved.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11699/84593
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