Massimo Imazio1, Antonio Brucato2, Paolo Ferrazzi2, Alberto Pullara3, Yehuda Adler4, Alberto Barosi5, Alida L Caforio6, Roberto Cemin7, Fabio Chirillo8, Chiara Comoglio9, Diego Cugola2, Davide Cumetti2, Oleksandr Dyrda9, Stefania Ferrua10, Yaron Finkelstein11, Roberto Flocco12, Anna Gandino5, Brian Hoit13, Francesco Innocente2, Silvia Maestroni2, Francesco Musumeci14, Jae Oh15, Amedeo Pergolini14, Vincenzo Polizzi14, Arsen Ristic16, Caterina Simon2, David H Spodick17, Vincenzo Tarzia6, Stefania Trimboli9, Anna Valenti2, Riccardo Belli18, Fiorenzo Gaita3. 1. Cardiology Department, Maria Vittoria Hospital, Torino, Italy2University of Torino, Torino, Italy. 2. Ospedale Papa Giovanni XXIII, Bergamo, Italy. 3. University of Torino, Torino, Italy4AOU Città della Salute e della Scienza di Torino, Torino, Italy. 4. Chaim Sheba Medical Center, Tel Hashomer and Sacker University, Tel Aviv, Israel. 5. Department of Internal Medicine and Cardiac Surgery, Ospedale Niguarda, Milano, Italy. 6. Department of Cardiological Thoracic and Vascular Sciences, University of Padova, Padova, Italy. 7. Cardiology Department, Ospedale Regionale San Maurizio, Bolzano, Italy. 8. Department of Cardiology and Cardiac Surgery, Ca Foncello Hospital, Treviso, Italy. 9. Department of Cardiac Surgery and Rehabilitation, Villa Maria Pia Hospital, Torino, Italy. 10. Department of Cardiology, Ospedale degli Infermi, Rivoli, Italy. 11. Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada. 12. Cardiac Surgery, Ospedale Mauriziano, Torino, Italy. 13. Case Western Reserve University, Cleveland, Ohio15University Hospitals Case Medical Center, Cleveland, Ohio. 14. Department of Cardiac Surgery, Ospedale San Camillo, Roma, Italy. 15. Division of Cardiovascular Disease, Mayo Clinic, Rochester, Minnesota. 16. Department of Cardiology, Belgrade University School of Medicine and Clinical Centre of Serbia, Belgrade, Serbia. 17. St Vincent Hospital, Worcester, Massachusetts. 18. Cardiology Department, Maria Vittoria Hospital, Torino, Italy.
Abstract
IMPORTANCE: Postpericardiotomy syndrome, postoperative atrial fibrillation (AF), and postoperative effusions may be responsible for increased morbidity and health care costs after cardiac surgery. Postoperative use of colchicine prevented these complications in a single trial. OBJECTIVE: To determine the efficacy and safety of perioperative use of oral colchicine in reducing postpericardiotomy syndrome, postoperative AF, and postoperative pericardial or pleural effusions. DESIGN, SETTING, AND PARTICIPANTS: Investigator-initiated, double-blind, placebo-controlled, randomized clinical trial among 360 consecutive candidates for cardiac surgery enrolled in 11 Italian centers between March 2012 and March 2014. At enrollment, mean age of the trial participants was 67.5 years (SD, 10.6 years), 69% were men, and 36% had planned valvular surgery. Main exclusion criteria were absence of sinus rhythm at enrollment, cardiac transplantation, and contraindications to colchicine. INTERVENTIONS: Patients were randomized to receive placebo (n=180) or colchicine (0.5 mg twice daily in patients ≥70 kg or 0.5 mg once daily in patients <70 kg; n=180) starting between 48 and 72 hours before surgery and continued for 1 month after surgery. MAIN OUTCOMES AND MEASURES: Occurrence of postpericardiotomy syndrome within 3 months; main secondary study end points were postoperative AF and pericardial or pleural effusion. RESULTS: The primary end point of postpericardiotomy syndrome occurred in 35 patients (19.4%) assigned to colchicine and in 53 (29.4%) assigned to placebo (absolute difference, 10.0%; 95% CI, 1.1%-18.7%; number needed to treat = 10). There were no significant differences between the colchicine and placebo groups for the secondary end points of postoperative AF (colchicine, 61 patients [33.9%]; placebo, 75 patients [41.7%]; absolute difference, 7.8%; 95% CI, -2.2% to 17.6%) or postoperative pericardial/pleural effusion (colchicine, 103 patients [57.2%]; placebo, 106 patients [58.9%]; absolute difference, 1.7%; 95% CI, -8.5% to 11.7%), although there was a reduction in postoperative AF in the prespecified on-treatment analysis (placebo, 61/148 patients [41.2%]; colchicine, 38/141 patients [27.0%]; absolute difference, 14.2%; 95% CI, 3.3%-24.7%). Adverse events occurred in 21 patients (11.7%) in the placebo group vs 36 (20.0%) in the colchicine group (absolute difference, 8.3%; 95% CI; 0.76%-15.9%; number needed to harm = 12), but discontinuation rates were similar. No serious adverse events were observed. CONCLUSIONS AND RELEVANCE: Among patients undergoing cardiac surgery, perioperative use of colchicine compared with placebo reduced the incidence of postpericardiotomy syndrome but not of postoperative AF or postoperative pericardial/pleural effusion. The increased risk of gastrointestinal adverse effects reduced the potential benefits of colchicine in this setting. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01552187.
RCT Entities:
IMPORTANCE: Postpericardiotomy syndrome, postoperative atrial fibrillation (AF), and postoperative effusions may be responsible for increased morbidity and health care costs after cardiac surgery. Postoperative use of colchicine prevented these complications in a single trial. OBJECTIVE: To determine the efficacy and safety of perioperative use of oral colchicine in reducing postpericardiotomy syndrome, postoperative AF, and postoperative pericardial or pleural effusions. DESIGN, SETTING, AND PARTICIPANTS: Investigator-initiated, double-blind, placebo-controlled, randomized clinical trial among 360 consecutive candidates for cardiac surgery enrolled in 11 Italian centers between March 2012 and March 2014. At enrollment, mean age of the trial participants was 67.5 years (SD, 10.6 years), 69% were men, and 36% had planned valvular surgery. Main exclusion criteria were absence of sinus rhythm at enrollment, cardiac transplantation, and contraindications to colchicine. INTERVENTIONS:Patients were randomized to receive placebo (n=180) or colchicine (0.5 mg twice daily in patients ≥70 kg or 0.5 mg once daily in patients <70 kg; n=180) starting between 48 and 72 hours before surgery and continued for 1 month after surgery. MAIN OUTCOMES AND MEASURES: Occurrence of postpericardiotomy syndrome within 3 months; main secondary study end points were postoperative AF and pericardial or pleural effusion. RESULTS: The primary end point of postpericardiotomy syndrome occurred in 35 patients (19.4%) assigned to colchicine and in 53 (29.4%) assigned to placebo (absolute difference, 10.0%; 95% CI, 1.1%-18.7%; number needed to treat = 10). There were no significant differences between the colchicine and placebo groups for the secondary end points of postoperative AF (colchicine, 61 patients [33.9%]; placebo, 75 patients [41.7%]; absolute difference, 7.8%; 95% CI, -2.2% to 17.6%) or postoperative pericardial/pleural effusion (colchicine, 103 patients [57.2%]; placebo, 106 patients [58.9%]; absolute difference, 1.7%; 95% CI, -8.5% to 11.7%), although there was a reduction in postoperative AF in the prespecified on-treatment analysis (placebo, 61/148 patients [41.2%]; colchicine, 38/141 patients [27.0%]; absolute difference, 14.2%; 95% CI, 3.3%-24.7%). Adverse events occurred in 21 patients (11.7%) in the placebo group vs 36 (20.0%) in the colchicine group (absolute difference, 8.3%; 95% CI; 0.76%-15.9%; number needed to harm = 12), but discontinuation rates were similar. No serious adverse events were observed. CONCLUSIONS AND RELEVANCE: Among patients undergoing cardiac surgery, perioperative use of colchicine compared with placebo reduced the incidence of postpericardiotomy syndrome but not of postoperative AF or postoperative pericardial/pleural effusion. The increased risk of gastrointestinal adverse effects reduced the potential benefits of colchicine in this setting. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01552187.
Authors: Alan Sugrue; Ammar M Killu; David O Hodge; Christopher J McLeod; Thomas M Munger; Siva K Mulpuru; Douglas L Packer; Suraj Kapa; Samuel J Asirvatham; Paul A Friedman Journal: J Interv Card Electrophysiol Date: 2016-12-09 Impact factor: 1.900