Hot Line: Does colchicine reduce the incidence of perioperative AF and myocardial injury in patients undergoing major non-cardiac thoracic surgery?
26 Aug 2023
Perioperative atrial fibrillation (AF) and myocardial injury after non-cardiac surgery (MINS) are common complications after non-cardiac surgery, and the pathogenesis of both has been linked to inflammation.1 As explained by Associate Professor David Conen (Population Health Research Institute - Hamilton, Canada) in a Hot Line session yesterday, the COP-AF trial was conducted to evaluate whether colchicine could reduce the incidence of perioperative AF and MINS.
HOT Line COpAF.jpg This international blinded trial included 3,209 patients aged 55 years or older who were undergoing major non-cardiac thoracic surgery. The mean age was 68 years and 48% were women. Participants were randomised to receive oral colchicine 0.5 mg twice daily or matching placebo, starting within 4 hours before surgery and continuing for 10 days.
There was no difference between the groups for the co-primary outcomes of clinically important perioperative AF or MINS.
AF needing medical treatment or AF leading to heart failure, hypotension or angina during 14 days of follow up developed in 6.4% of patients assigned to colchicine and 7.5% of patients assigned to placebo (hazard ratio [HR] 0.85; 95% CI 0.65 to 1.10), with an absolute risk reduction (ARR) of 1.1% (95% CI –0.7 to 2.8, p=0.22). MINS – defined as myocardial infarction (MI) or any postoperative troponin elevation deemed to be of ischaemic origin – occurred in 18.3% of patients in the colchicine group and 20.3% of patients in the placebo group (HR 0.89; 95% CI 0.76 to 1.05) and the ARR was 2.0% (95% CI –0.8 to 4.7; p=0.16).
There were no significant differences between treatment groups in key secondary outcomes, including the composite of all-cause mortality, nonfatal MINS and nonfatal stroke; the composite of all-cause mortality, nonfatal MI and nonfatal stroke; MINS not fulfilling the fourth universal definition of MI; and MI. However, in post-hoc analyses, the composite outcome of clinically important perioperative AF or MINS appeared to occur less frequently with colchicine than placebo (22.4% versus 25.9%; HR 0.84; 95% CI 0.73 to 0.97). Similarly, vascular mortality, nonfatal MINS, nonfatal stroke or clinically important perioperative AF was observed in 22.6% with colchicine and 26.4% with placebo (HR 0.83; 95% CI 0.72 to 0.96). Stroke occurred in 1 patient (0.1%) in the colchicine group and 5 (0.3%) in the placebo group (p=0.12).
From a safety perspective, a composite of sepsis or infection occurred in 6.4% of patients in the colchicine group and 5.2% of patients in the placebo group (HR 1.24; 95% CI 0.93 to 1.66). Colchicine increased the incidence of non-infectious diarrhoea (8.3% versus 2.4%; HR 3.64; 95% CI 2.54 to 5.22), but Dr. Conen comments that “these episodes were temporary and benign.” No treatment was required in 38.4% of cases of diarrhoea, with 8.7% of patients needing intravenous hydration.
He concludes: “Several results provide an encouraging signal of benefit for colchicine to reduce the incidence of adverse CV outcomes in patients undergoing major non-cardiac thoracic surgery. Future trials should further investigate the role of colchicine in the prevention of these events in patients undergoing surgery.”
References
- Conen D, et al. Am Heart J. 2023;259:87–96.
