title: Colchicine for prevention of postpericardiotomy syndrome and postoperative atrial fibrillation: the COPPS-2 randomized clinical trial.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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
  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.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01552187.
authors.affiliation: Cardiology Department, Maria Vittoria Hospital, Torino, Italy2University of Torino, Torino, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Imazio
authors.affiliation: Ospedale Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Brucato
authors.affiliation: Ospedale Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Ferrazzi
authors.affiliation: University of Torino, Torino, Italy4AOU Città della Salute e della Scienza di Torino, Torino, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Pullara
authors.affiliation: Chaim Sheba Medical Center, Tel Hashomer and Sacker University, Tel Aviv, Israel.
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Adler
authors.affiliation: Department of Internal Medicine and Cardiac Surgery, Ospedale Niguarda, Milano, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Barosi
authors.affiliation: Department of Cardiological Thoracic and Vascular Sciences, University of Padova, Padova, Italy.
authors.forename: Alida L
authors.initials: AL
authors.lastname: Caforio
authors.affiliation: Cardiology Department, Ospedale Regionale San Maurizio, Bolzano, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Cemin
authors.affiliation: Department of Cardiology and Cardiac Surgery, Ca Foncello Hospital, Treviso, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Chirillo
authors.affiliation: Department of Cardiac Surgery and Rehabilitation, Villa Maria Pia Hospital, Torino, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Comoglio
authors.affiliation: Ospedale Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Cugola
authors.affiliation: Ospedale Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Cumetti
authors.affiliation: Department of Cardiac Surgery and Rehabilitation, Villa Maria Pia Hospital, Torino, Italy.
authors.forename: Oleksandr
authors.initials: O
authors.lastname: Dyrda
authors.affiliation: Department of Cardiology, Ospedale degli Infermi, Rivoli, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Ferrua
authors.affiliation: Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Yaron
authors.initials: Y
authors.lastname: Finkelstein
authors.affiliation: Cardiac Surgery, Ospedale Mauriziano, Torino, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Flocco
authors.affiliation: Department of Internal Medicine and Cardiac Surgery, Ospedale Niguarda, Milano, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Gandino
authors.affiliation: Case Western Reserve University, Cleveland, Ohio15University Hospitals Case Medical Center, Cleveland, Ohio.
authors.forename: Brian
authors.initials: B
authors.lastname: Hoit
authors.affiliation: Ospedale Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Innocente
authors.affiliation: Ospedale Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Maestroni
authors.affiliation: Department of Cardiac Surgery, Ospedale San Camillo, Roma, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Musumeci
authors.affiliation: Division of Cardiovascular Disease, Mayo Clinic, Rochester, Minnesota.
authors.forename: Jae
authors.initials: J
authors.lastname: Oh
authors.affiliation: Department of Cardiac Surgery, Ospedale San Camillo, Roma, Italy.
authors.forename: Amedeo
authors.initials: A
authors.lastname: Pergolini
authors.affiliation: Department of Cardiac Surgery, Ospedale San Camillo, Roma, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Polizzi
authors.affiliation: Department of Cardiology, Belgrade University School of Medicine and Clinical Centre of Serbia, Belgrade, Serbia.
authors.forename: Arsen
authors.initials: A
authors.lastname: Ristic
authors.affiliation: Ospedale Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Simon
authors.affiliation: St Vincent Hospital, Worcester, Massachusetts.
authors.forename: David H
authors.initials: DH
authors.lastname: Spodick
authors.affiliation: Department of Cardiological Thoracic and Vascular Sciences, University of Padova, Padova, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Tarzia
authors.affiliation: Department of Cardiac Surgery and Rehabilitation, Villa Maria Pia Hospital, Torino, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Trimboli
authors.affiliation: Ospedale Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Valenti
authors.affiliation: Cardiology Department, Maria Vittoria Hospital, Torino, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Belli
authors.affiliation: University of Torino, Torino, Italy4AOU Città della Salute e della Scienza di Torino, Torino, Italy.
authors.forename: Fiorenzo
authors.initials: F
authors.lastname: Gaita
mesh_terms: D000368:Aged; D001281:Atrial Fibrillation / Q000517:prevention & control*; D006348:Cardiac Surgical Procedures; D003078:Colchicine / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D010490:Pericardial Effusion / Q000517:prevention & control; D019990:Perioperative Care; D010996:Pleural Effusion / Q000517:prevention & control; D011183:Postoperative Complications / Q000517:prevention & control*; D011185:Postpericardiotomy Syndrome / Q000517:prevention & control*; D050257:Tubulin Modulators / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D050257:Tubulin Modulators; D003078:Colchicine