Colchicine for the Prevention of Perioperative Atrial Fibrillation in Patients Undergoing Thoracic Surgery - COP-AF

Aug 25, 2023
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Author/Summarized by Author:
Amit Saha, MD
Summary Reviewer:
Dharam J. Kumbhani, MD, SM, FACC
Trial Sponsor:
Canadian Institutes of Health Research; Population Health Research Institute; McMaster University, Hamilton, Canada.
Date Presented:
08/25/2023
Date Published:
08/25/2023
Original Posted Date:
08/25/2023
References

Contribution To Literature:

The COP-AF trial showed that in patients undergoing major noncardiac thoracic surgery, colchicine did not reduce the incidence of perioperative AF or MINS compared with placebo.

Description:

The goal of the trial was to determine the effect of colchicine on perioperative atrial fibrillation (AF) or myocardial injury after noncardiac surgery (MINS) compared with placebo in patients undergoing major noncardiac thoracic surgery.

Study Design

  • Randomized
  • International, multicenter
  • Double-blind

Patients undergoing noncardiac thoracic surgery were randomized to receive colchicine 0.5 mg twice daily (n = 1,608) or matching placebo (n = 1,601). Study drug was first administered within 4 hours preoperatively for a total duration of 10 days. Daily cardiac troponin was collected on postoperative days 1 to 3. Rhythm monitoring was conducted per site routine, but daily ECG on postoperative days 1 to 3 were encouraged.

  • Total number of enrollees: 3,209
  • Duration of follow-up: 14 days
  • Mean patient age: 68 years
  • Percentage female: 48.4%

Inclusion criteria:

  • Age ≥55 years
  • Major noncardiac thoracic surgery (excluding lung transplantation) with general anesthesia
  • Anticipated need for at least overnight hospital admissions

Exclusion criteria:

  • Previously diagnosed AF
  • Class I or III antiarrhythmic drug use
  • Unable to take oral medication for >24 hours postoperatively
  • Allergy or contraindication to colchicine (e.g., estimated glomerular filtration rate <30 mL/min/1.73 m2)
  • Currently taking colchicine
  • Severe hepatic dysfunction
  • Aplastic anemia
  • Antiretroviral therapy for human immunodeficiency virus

Other salient features/characteristics:

  • Percentage with known coronary artery disease: 8.9%
  • Percentage undergoing thoracoscopic surgery: 74.7%
  • Lobectomy (63.6%) was the most common surgery
  • Study drug discontinuation, colchicine vs. placebo: 17.0% vs. 12.6%

Principal Findings:

Coprimary outcomes for colchicine vs. placebo:

  • Clinically significant perioperative AF1: 6.4% vs. 7.5%, p = 0.22
  • MINS: 18.3% vs. 20.3%, p = 0.16

1Clinically significant AF: associated with angina, heart failure, or symptomatic hypotension or requiring rate or pharmacologic/electrical cardioversion.

Post hoc composite of coprimary outcomes for colchicine vs. placebo: 22.4% vs. 25.9% (hazard ratio 0.84, 95% confidence interval 0.73-0.97)

Secondary outcomes for colchicine vs. placebo:

  • Composite of all-cause mortality, nonfatal MINS, and nonfatal stroke: 18.7% vs. 20.9%, p = 0.11
  • Myocardial infarction: 0.8% vs. 0.9%, p = 0.69
  • Hospital length of stay: 5.0 vs. 5.0 days, p = 0.48

Safety outcomes for colchicine vs. placebo:

  • Composite of sepsis and infection: 6.4% vs. 5.2%, p = 0.14
  • Noninfectious diarrhea: 8.3% vs. 2.4%, p < 0.0001

Interpretation:

The COP-AF study did not observe a reduction in clinically significant perioperative AF or MINS with colchicine compared with placebo in patients undergoing major noncardiac thoracic surgery. Perioperative AF and MINS are more common in patients with elevated inflammatory biomarkers and have been associated with worse short- and long-term postoperative outcomes. This has generated continued interest in the potential cardioprotective effect of colchicine, which may be of some benefit. Though negative, COP-AF provides the first randomized, large-scale data examining the efficacy of colchicine in noncardiac surgery.

Given site variability in postoperative cardiac monitoring, with <50% of patients undergoing ECG on postoperative day 3, total AF events may have been undercounted. However, their silent nature suggests they would likely not have been clinically significant. Moreover, colchicine was associated with greater rates of study drug discontinuation primarily due to the frequency of noninfectious diarrhea. Post hoc analysis suggests that composite outcomes comprising AF and other adverse cardiovascular events may be fruitful avenues of future investigation into the potential cardioprotective effects of colchicine in noncardiac surgery.

References:

Conen D, Wang MK, Popova E, et al., on behalf of the COP-AF Investigators. Effect of colchicine on perioperative atrial fibrillation and myocardial injury after non-cardiac surgery in patients undergoing major thoracic surgery (COP-AF): an international randomized trial. Lancet 2023;Aug 25:[Epub ahead of print].

Presented by Dr. David Conen at the European Society of Cardiology Congress, Amsterdam, Netherlands, August 25, 2023.

Clinical Topics: Arrhythmias and Clinical EP, Prevention, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias

Keywords: Arrhythmias, Cardiac, Atrial Fibrillation, Colchicine, ESC Congress, ESC23, Secondary Prevention, Thoracic Surgery


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