COP-AF - Colchicine for the prevention of perioperative atrial fibrillation after major thoracic surgery

Presented at the ESC Congress 2023 by: David Conen, MD - Hamilton, ON, Canada

Introduction and methods

Colchicine is an anti-inflammatory drug that has been previously be found to reduce post-operative AF events in patients undergoing cardiac surgery, as well as major CV events in patients with CAD.

The aim of the study was to investigate the effects of oral colchicine on the incidence of perioperative AF and myocardial injury after non-cardiac surgery (MINS) in patients undergoing major thoracic surgery.

A total of 3209 patients (>55 years) undergoing major non-cardiac thoracic surgery were included in the study. Patients were randomized in a 1:1 ratio to receive oral colchicine 0.5mg twice daily or placebo for 10 days. The first dose was administered within 4h before surgery. Patients were followed for a duration of 14 days.

The co-primary outcomes were clinically important AF (defined as AF resulting in angina, HF or symptomatic hypotension or AF requiring treatment with rate-controlling drug, antiarrhythmic drug or electrical cardioversion) and MINS (defined as a MI, or an elevated postoperative troponin that was thought to be of ischemic origin).

Main results

Co-primary outcomes

• Colchicine did not significantly lower the incidence of clinically important perioperative AF in patients undergoing major non-cardiac thoracic surgery compared with placebo (6.4% vs. 7.5%; HR: 0.85; 95%CI: 0.65-1.10; P=0.22).
• Treatment with colchicine also did not lower the incidence of MINS compared with placebo in these patients (18.3% vs. 20.3%; HR: 0.89; 95%CI: 0.76-1.05; P=0.16).

Main secondary outcomes

• Colchicine did not reduce the risk of the composite of all-cause mortality, nonfatal MINS and nonfatal stroke (HR: 0.88; 95%CI: 0.75-1.03; P=0.11); the composite of all-cause mortality, nonfatal MI and nonfatal stroke (HR: 0.67; 95%CI: 0.39-1.17; P=0.16); MINS not fulfilling the fourth universal definition of MI (HR: 0.90; 95%CI: 0.76-1.06; P=0.22); or MI (HR: 0.86; 95%CI: 0.41-1.81; P=0.69).

Safety outcomes

• The incidence of the composite of sepsis and infection was comparable between treatment groups (6.4% in the colchicine group vs. 5.2% in the placebo group; HR: 1.24; 95%CI: 0.93-1.66; P=0.14).
• Treatment with colchicine increased the incidence of non-infectious diarrhea (8.3% vs. 2.4%; HR: 3.64; 95%CI: 2.54-5.22; P<0.001). These events were mostly benign and transient, and led only in 1 patient to readmission.

Post-hoc analyses

• Colchicine reduced the risk of the composite of MINS and clinically important AF (HR: 0.84; 95%CI: 0.73-0.97; P=0.02).
• Colchicine reduced the risk of the composite of vascular mortality, nonfatal MINS, nonfatal stroke and clinically important AF (HR: 0.83; 95%CI: 0.72-0.96; P=0.01).

Conclusion

Colchicine did not reduce the incidence of the co-primary outcomes of clinically important perioperative AF or MINS in patients undergoing major non-cardiac thoracic surgery. Colchicine treatment was associated with an higher incidence of, mostly transient and benign, diarrhea. Presenter David Conen said “there was an encouraging trend of fewer cardiovascular events with colchicine that was in line with previous studies. We think more studies are needed to evaluate the role of colchicine in patients undergoing surgery”.

- Our reporting is based on the information provided at the ESC Congress 2023 -

The results of this study were simultaneously published in The Lancet Watch the video with Dadvid Conen about COP-AF