A group of researchers from various departments at the Hospital de Sant Pau and the Research Group in Clinical Epidemiology and Healthcare Services of the IIB Sant Pau has published a study in The Lancet that provides promising results regarding colchicine as a reducer of cardiovascular complications in patients undergoing major thoracic surgery. In this study, titled “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,” 45 hospitals from 11 countries around the world participated. In Spain, 7 centers and 765 patients took part, with 275 of them coming from Sant Pau Hospital, making it one of the primary recruiting centers.
The COP-AF study is a large international and multicenter clinical trial that included patients undergoing thoracic surgery who were administered an anti-inflammatory drug like colchicine versus a placebo to reduce the risk of perioperative atrial fibrillation (AF – a cardiac arrhythmia) or myocardial injury after non-cardiac surgery (MINS – Myocardial injury after non-cardiac surgery). Perioperative AF and MINS have approximate incidences of 10% and 20%, respectively, and are common complications following major thoracic surgery.
Elevated levels of inflammatory biomarkers have been associated with a higher risk of perioperative AF and MINS. In this regard, the COP-AF study tested the hypothesis that anti-inflammatory treatment could reduce the incidence of these two significant complications.
The trial included a total of 3,209 patients aged 55 years or older in 45 hospitals from 11 countries worldwide (Austria, Belgium, Canada, China, Colombia, Italy, Malaysia, Pakistan, Spain, Switzerland, and the United States). In Spain, 7 hospitals and a total of 765 patients participated, with 275 of them from Sant Pau Hospital, one of the primary recruiters for this study.
The research findings were presented at the European Society of Cardiology (ESC) Congress, held recently in Amsterdam, the Netherlands, by the lead international investigator, Dr. David Conen, a scientist at the Population Health Research Institute (PHRI) and associate professor of Medicine at McMaster University in Hamilton, Canada.
The primary investigators from Hospital de Sant Pau and IIB Sant Pau were Dr. Juan Carlos Trujillo and Dr. Elisabeth Martínez-Tellez from the Thoracic Surgery Department of the Hospital, and Dr. Ekaterine Popova from the Research Group in Clinical Epidemiology, Public Health, and Primary Care at IIB Sant Pau. They worked collaboratively with professionals from the departments of Thoracic Surgery (Dr. Josep Belda Sanchis, Dr. Alejandra Libreros, Dr. Georgina Planaz, Dr. Esther Cladellas, and Dr. Mauro Guarino), Epidemiology (Dr. Gerard Urrutia, Dr. Melixa Medina, and Ibell Araúz), Anesthesiology and Resuscitation (Dr. Ana Parera, Dr. Marta Argilaga, Dr. Josep Mª Gil, and Dr. Gracia Herranz), Nursing (Anna Rovira and Asunción Turró), Cardiology (Dr. Jose Guerra, Dr. Zoraida Moreno, Dr. Francisco Méndez, Dr. Jesús Àlvarez), Traumatology (Dr. Aranzazu González), Neurology (Dr. Anna Ramos-Pachón), Clinical Biochemistry (Dr. Álvaro García), and Pharmacy (Ainhoa Rodríguez-Arias and Nuria Berga).
Half of the patients were randomly assigned to receive 0.5 mg of colchicine, while the other half received a matching placebo. Both the research staff and the patients were unaware of the treatment assignment. The first dose of the study treatment was administered within 4 hours before surgery and continued twice daily for a total of 10 days.
Clinically significant AF occurred in 103 out of 1,608 (6.4%) patients assigned to colchicine and in 120 out of 1,601 (7.5%) patients assigned to placebo, with a hazard ratio (HR) of 0.85 (95% confidence interval [CI] 0.65 to 1.10), p=0.22. MINS occurred in 295 (18.3%) patients assigned to colchicine and in 325 (20.3%) patients assigned to placebo, with an HR of 0.89 (95% CI 0.76 to 1.05), p=0.16. However, the composite outcome of clinically significant AF or MINS occurred in 360 (22.4%) patients in the colchicine group and 415 (25.9%) patients in the placebo group (HR 0.84; 95% CI 0.73 to 0.97), p=0.02.
Dr. Juan Carlos Trujillo, clinical head of the Thoracic Surgery Department at Sant Pau Hospital and one of the main investigators of the study, pointed out that “although colchicine did not significantly reduce the incidence of the co-primary outcomes of clinically significant perioperative AF or MINS, it did significantly reduce the composite of the two co-primary outcomes.”
Dr. Ekaterine Popova, researcher from the Group in Clinical Epidemiology and Healthcare Services at IIB Sant Pau, stated, “While not definitive, the overall results of the trial provide a hopeful signal of benefit for colchicine in reducing the incidence of adverse cardiovascular complications in patients undergoing major thoracic surgery.” She added that “colchicine significantly increased the risk of non-infectious diarrhea, but the data indicate that these episodes were temporary and mild.”
Adverse cardiovascular complications are the most common among the 300 million patients who undergo non-cardiac surgery each year worldwide. According to experts, urgent interventions are needed to reduce this risk. The results of this trial support the importance of further investigating the role of colchicine in preventing these episodes in patients undergoing non-cardiac surgery.
David Conen, Michael Ke Wang, Ekaterine Popova, Matthew T V Chan, Giovanni Landoni, Juan P Cata, Cara Reimer, Sean R McLean, Sadeesh K Srinathan, Juan Carlos Trujillo Reyes, Ascension Martín Grande, Anna Gonzalez Tallada, Daniel I Sessler, Edith Fleischmann, Barbara Kabon, Luca Voltolini, Patrícia Cruz, Donna E Maziak, Laura Gutiérrez-Soriano, William F McIntyre, Vikas Tandon, Elisabeth Martínez-Téllez, Juan Jose Guerra-Londono, Deborah DuMerton, Randolph H L Wong, Anna L McGuire, Biniam Kidane, Diego Parise Roux, Yaron Shargall, Jennifer R Wells, Sandra N Ofori, Jessica Vincent, Lizhen Xu, Zhuoru Li, John W Eikelboom, Sanjit S Jolly, Jeff S Healey, P J Devereaux, 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 randomised trial”. Published online August 25, 2023 https://doi.org/10.1016/S0140-6736(23)01689-6
