COP-AF: Colchicine did not reduce AF or myocardial injury after non-cardiac surgery, but post-hoc analysis suggest benefit in composite outcomes

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By Lucas Marinacci on

Key Points

  • This trial randomizing patients aged 55 or older to colchicine or placebo following non-cardiac thoracic surgery found no difference in the co-primary endpoints of atrial fibrillation or myocardial injury, but post-hoc analyses indicated benefit in composite outcomes without a signal for increased harm.
  • Colchicine increased risk of diarrhea, but patients reported that these symptoms were mostly temporary and benign.
  • Further research is needed to explore the encouraging and consistent trend of fewer cardiovascular events with colchicine after non-cardiac surgery.

Atrial fibrillation (AF) and myocardial injury following non-cardiac surgery (MINS) are both common perioperative complications associated with increased rates of stroke, cardiovascular events, and death.1–3  While inflammatory biomarkers are elevated in both AF and MINS, it is unknown whether anti-inflammatory therapies lowers their incidence or improves cardiovascular outcomes following non-cardiac surgery.  In prior randomized trials, colchicine has been shown to reduce the incidence of atrial fibrillation following cardiac surgery and has also been shown to have benefit in chronic coronary artery disease.4, 5

 

On August 25th, 2023 the results of the Colchicine For The Prevention Of Perioperative Atrial Fibrillation In Patients Undergoing Thoracic Surgery (COP-AF) were presented in a Hot Line Session at ESC Congress 2023.   In this multinational, parallel-group, triple-masked clinical trial randomized patients aged 55 and older without a diagnosis of AF undergoing non-cardiac thoracic surgery to colchicine 0.5mg twice a day for 10 days or placebo starting 4 hours before their operation.6  The primary outcome measures were clinically important AF (defined as needing treating or causing heart failure, hypotension, or angina) or MINS within 14 days of randomization.

 

Overall, 3209 patients were randomized.  The mean age was 68 years; 51.6% were male.  The rates of AF and MINS were lower in the colchicine arm compared to the placebo arm, but did not reach statistical significance (6.4% vs 7.5%, HR 0.85, 95% CI 0.65-1.10, p =0.22 and 18.3% vs. 20.3%, HR 0.89, 95% CI 0.76-1.05, p=0.16, respectively).  Similarly, no significant differences were found in all-cause mortality or stroke.

 

However, in a post-hoc analysis, there was a reduction in the combined outcome of AF or MINS in the colchicine arm (22.4% vs. 25.9%, HR 0.84, 95% CI 0.73-0.97; p = 0.02) as well as composite outcome of vascular mortality, nonfatal MINS, non-fatal stroke, or AF (22.6% vs 26.4%, HR 0.83, 95% CI 0.72-0.96; p =0.01).  No significant difference was found in the composite safety outcome of sepsis or infection.  Non-infectious diarrhea was more than three time  more common in the colchicine arm compared to placebo (8.3%) versus 38 (2.4%) respectively [HR 3.64 (95% CI 2.54 to 5.22)], without a significant increase in length of stay.

According to principal investigator Dr. David Conen of the Population Health Research Institute, Hamilton, Canada: “Colchicine did not significantly reduce the incidence of the co-primary outcomes of clinically important perioperative AF or MINS… Despite these findings, post-hoc analyses provide an encouraging signal of benefit for colchicine to reduce the incidence of adverse cardiovascular outcomes in patients undergoing major non-cardiac thoracic surgery.”

 

 

References

  1. Devereaux PJ, Biccard BM, Sigamani A, et al. Association of Postoperative High-Sensitivity Troponin Levels With Myocardial Injury and 30-Day Mortality Among Patients Undergoing Noncardiac Surgery. JAMA. 2017;317:1642.
  2. Brathwaite D, Weissman C. The new onset of atrial arrhythmias following major noncardiothoracic surgery is associated with increased mortality. Chest. 1998;114:462–8.
  3. Conen D, Alonso-Coello P, Douketis J, et al. Risk of stroke and other adverse outcomes in patients with perioperative atrial fibrillation 1 year after non-cardiac surgery. Eur Heart J. 2020;41:645–651.
  4. Zhao H, Chen Y, Mao M, Yang J, Chang J. A meta-analysis of colchicine in prevention of atrial fibrillation following cardiothoracic surgery or cardiac intervention. J Cardiothorac Surg. 2022;17:1–9.
  5. Nidorf SM, Fiolet ATL, Mosterd A, et al. Colchicine in Patients with Chronic Coronary Disease. N Engl J Med. 2020;383:1838–1847.
  6. Conen D, Popova E, Wang MK, et al. Rationale and design of the colchicine for the prevention of perioperative atrial fibrillation in patients undergoing major noncardiac thoracic surgery (COP-AF) trial. Am Heart J. 2023;259:87–96.