Smoking, Colchicine and Postoperative Outcomes in Thoracic Surgery: Post Hoc Analysis of the COP-AF Randomized Controlled Trial

Background: To determine, among patients who underwent major noncardiac thoracic surgery, the association between smoking and perioperative atrial fibrillation (AF) and myocardial injury after noncardiac surgery (MINS), and whether the effect of colchicine use on these outcomes varied by smoking status. Methods: This study is a subgroup analysis of the Colchicine for the Prevention of Perioperative Atrial Fibrillation (COP-AF) randomized clinical trial. A total of 3209 participants who underwent major noncardiac thoracic surgery were randomized to receive colchicine, 0.5 mg twice daily, or identical placebo, for 10 days starting 2-4 hours before surgery. The co-primary outcomes were clinically significant perioperative AF and MINS during the 14-day follow-up. Results: A total of 687 (21.4%) were current smokers, 1577 (49.1%) were former smokers, and 945 (29.5%) were never smokers. AF occurred in 7.7%, 7.6%, and 5.3%, and MINS occurred in 21.0%, 19.7%, and 17.6% of current, former, and never smokers, respectively. Compared to never smokers, the adjusted hazard ratio for AF was 1.72 (95% confidence interval [CI] 1.07-2.77, P = 0.02) in current smokers and 1.46 (95% CI 0.99-2.16, P = 0.06) in former smokers, and the adjusted hazard ratio for MINS was 1.16 (95% CI 0.87-1.54, P = 0.32) in current smokers and 1.02 (95% CI 0.81-1.28, P = 0.88) in former smokers. No interaction occurred between smoking status and colchicine allocation for AF (interaction P, 0.82) or MINS (interaction P, 0.08). Conclusions: Current smoking was associated with a small but increased risk of perioperative AF but not MINS after thoracic surgery. The effect of colchicine use on either outcome was not modified by smoking status. Clinical Trial Registration: NCT03310125