Colchicine for prevention of postpericardiotomy syndrome and postoperative atrial fibrillation: the COPPS-2 randomized clinical trial
Massimo Imazio, Antonio Brucato, Paolo Ferrazzi, Alberto Pullara, Yehuda Adler, Alberto Barosi, Alida L Caforio, Roberto Cemin, Fabio Chirillo, Chiara Comoglio, Diego Cugola, Davide Cumetti, Oleksandr Dyrda, Stefania Ferrua, Yaron Finkelstein, Roberto Flocco, Anna Gandino, Brian Hoit, Francesco Innocente, Silvia Maestroni, Francesco Musumeci, Jae Oh, Amedeo Pergolini, Vincenzo Polizzi, Arsen Ristic, Caterina Simon, David H Spodick, Vincenzo Tarzia, Stefania Trimboli, Anna Valenti, Riccardo Belli, Fiorenzo Gaita, COPPS-2 Investigators, Massimo Imazio, Riccardo Belli, Antonio Brucato, Paolo Ferrazzi, Yaron Finkelstein, Anna Leggieri, Bernhard Maisch, Bongani Mayosi, Jae K Oh, Arsen D Ristic, Petar Seferovic, Yehuda Adler, Brian Hoit, David H Spodick, Alberto Pullara, Antonio Brucato, Paolo Ferrazzi, Diego Cugola, Davide Cumetti, Silvia Maestroni, Francesco Innocente, Anna Valenti, Lorenzo Galletti, Chiara Comoglio, Oleksandr Dyrda, Stefania Trimboli, Elisabetta Lardone, Paolo Sorrentino, Ingignoli Biagio, Roberto Valesio, Annarita Zeoli, Massimo Imazio, Riccardo Belli, Alessandra Chinaglia, Enrico Cecchi, Luisella Coda, Brunella Demichelis, Silvia Ferro, Davide Forno, Alberto Barosi, Anna Gandino, Luigi Martinelli, Cristina Giannattasio, Paola Sormani, Roberto Flocco, Riccardo Casabona, Fabio Chirillo, Marcio Scorsin, Zoran Olivari, Elvio Polesel, Vincenzo Polizzi, Emanuela Belmonte, Francesco Musumeci, Amedeo Pergolini, Roberto Cemin, Angelo Graffigna, Stefania Ferrua, Ferdinando Varbella, Alida L Caforio, Vincenzo Tarzia, Sabino Iliceto, Gino Gerosa, Piera Costanzo, Massimo Minelli, Massimo Imazio, Antonio Brucato, Paolo Ferrazzi, Alberto Pullara, Yehuda Adler, Alberto Barosi, Alida L Caforio, Roberto Cemin, Fabio Chirillo, Chiara Comoglio, Diego Cugola, Davide Cumetti, Oleksandr Dyrda, Stefania Ferrua, Yaron Finkelstein, Roberto Flocco, Anna Gandino, Brian Hoit, Francesco Innocente, Silvia Maestroni, Francesco Musumeci, Jae Oh, Amedeo Pergolini, Vincenzo Polizzi, Arsen Ristic, Caterina Simon, David H Spodick, Vincenzo Tarzia, Stefania Trimboli, Anna Valenti, Riccardo Belli, Fiorenzo Gaita, COPPS-2 Investigators, Massimo Imazio, Riccardo Belli, Antonio Brucato, Paolo Ferrazzi, Yaron Finkelstein, Anna Leggieri, Bernhard Maisch, Bongani Mayosi, Jae K Oh, Arsen D Ristic, Petar Seferovic, Yehuda Adler, Brian Hoit, David H Spodick, Alberto Pullara, Antonio Brucato, Paolo Ferrazzi, Diego Cugola, Davide Cumetti, Silvia Maestroni, Francesco Innocente, Anna Valenti, Lorenzo Galletti, Chiara Comoglio, Oleksandr Dyrda, Stefania Trimboli, Elisabetta Lardone, Paolo Sorrentino, Ingignoli Biagio, Roberto Valesio, Annarita Zeoli, Massimo Imazio, Riccardo Belli, Alessandra Chinaglia, Enrico Cecchi, Luisella Coda, Brunella Demichelis, Silvia Ferro, Davide Forno, Alberto Barosi, Anna Gandino, Luigi Martinelli, Cristina Giannattasio, Paola Sormani, Roberto Flocco, Riccardo Casabona, Fabio Chirillo, Marcio Scorsin, Zoran Olivari, Elvio Polesel, Vincenzo Polizzi, Emanuela Belmonte, Francesco Musumeci, Amedeo Pergolini, Roberto Cemin, Angelo Graffigna, Stefania Ferrua, Ferdinando Varbella, Alida L Caforio, Vincenzo Tarzia, Sabino Iliceto, Gino Gerosa, Piera Costanzo, Massimo Minelli
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.
Source: PubMed