Colchicine for prevention of postpericardiotomy syndrome and postoperative atrial fibrillation: the COPPS-2 randomized clinical trial.

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.

Colchicine reduces postoperative atrial fibrillation: results of the Colchicine for the Prevention of the Postpericardiotomy Syndrome (COPPS) atrial fibrillation substudy.

BACKGROUND: Inflammation and pericarditis may be contributing factors for postoperative atrial fibrillation (POAF), and both are potentially affected by antiinflammatory drugs and colchicine, which has been shown to be safe and efficacious for the prevention of pericarditis and the postpericardiotomy syndrome (PPS). The aim of the Colchicine for the Prevention of the Post-Pericardiotomy Syndrome (COPPS) POAF substudy was to test the efficacy and safety of colchicine for the prevention of POAF after cardiac surgery. METHODS AND RESULTS: The COPPS POAF substudy included 336 patients (mean age, 65.7±12.3 years; 69% male) of the COPPS trial, a multicenter, double-blind, randomized trial. Substudy patients were in sinus rhythm before starting the intervention (placebo/colchicine 1.0 mg twice daily starting on postoperative day 3 followed by a maintenance dose of 0.5 mg twice daily for 1 month in patients ≥70 kg, halved doses for patients <70 kg or intolerant to the highest dose). The substudy primary end point was the incidence of POAF on intervention at 1 month. Despite well-balanced baseline characteristics, patients on colchicine had a reduced incidence of POAF (12.0% versus 22.0%, respectively; P=0.021; relative risk reduction, 45%; number needed to treat, 11) with a shorter in-hospital stay (9.4±3.7 versus 10.3±4.3 days; P=0.040) and rehabilitation stay (12.1±6.1 versus 13.9±6.5 days; P=0.009). Side effects were similar in the study groups. CONCLUSION: Colchicine seems safe and efficacious in the reduction of POAF with the potentiality of halving the complication and reducing the hospital stay.

Colchicine prevents early postoperative pericardial and pleural effusions.

BACKGROUND: No preventive pharmacologic strategies have been proven efficacious for the prevention of postoperative effusions after cardiac surgery. Colchicine is safe and efficacious for the prevention of pericarditis. On this basis, we realized a substudy of the COPPS trial to assess the efficacy and safety of colchicine for the prevention of postoperative pericardial and pleural effusions. METHODS: The COPPS is a multicenter, double-blind, randomized trial, where 360 consecutive patients (mean age 65.7 ± 12.3 years, 66% men), 180 in each treatment arm, were randomized on the third postoperative day to receive placebo or colchicine for 1 month (1.0 mg twice daily for the first day, followed by a maintenance dose of 0.5 mg twice daily in patients ≥70 kg, and halved doses for patients <70 kg). The incidence of postoperative effusions was evaluated in each study group. RESULTS: Despite similar baseline features, colchicine significantly reduced the incidence of postoperative pericardial (12.8% vs 22.8%, P = .019, relative risk reduction 43.9%, no. of patients needed to treat 10) and pleural effusions (12.2% vs 25.6%, P = .002, relative risk reduction 52.3%, no. of patients needed to treat 8). The rate of side effects (only gastrointestinal intolerance) and drug withdrawal was similar in the study groups with a trend toward an increased rate of both events for colchicine. In multivariable analysis, female gender (hazard ratio 1.76, 95% CI 1.03-3.03, P = .040) and pleura incision (hazard ratio 2.58, 95% CI 1.53-4.53, P < .001) were risk factors for postoperative effusions. CONCLUSIONS: Colchicine is safe and efficacious for the primary prevention of postoperative effusions after cardiac surgery.

Contemporary features, risk factors, and prognosis of the post-pericardiotomy syndrome.

Contemporary series of postpericardiotomy syndrome (PPS) are lacking. The aim of this study was to evaluate the incidence, time course, features at presentation, risk factors, and prognosis of PPS. The study population consisted of 360 consecutive candidates to cardiac surgery enrolled in a prospective cohort study. PPS was diagnosed in 54 patients (15.0%; mean age 66 ± 12 years, 48.1% women): 79.6% in the first month, 13.0% in the second month, and 7.4% in the third month. Specific symptoms, signs, or features were pleuritic chest pain (55.6%), fever (53.7%), elevated markers of inflammation (74.1%), pericardial effusion (88.9%), and pleural effusion (92.6%). Cardiac tamponade was rare at presentation (1.9%). Female gender (hazard ratio 2.32, 95% confidence interval 1.22 to 4.39, p = 0.010), and pleura incision (hazard ratio 4.31, 95% confidence interval 2.22 to 8.33, p <0.001) were identified as risk factors in multivariate analysis. Patients with PPS had longer cardiac surgery stays (11.5 ± 4.6 vs 9.9 ± 4.7 days, p = 0.021) and rehabilitation stays (16.4 ± 6.7 vs 12.4 ± 6.2 days, p <0.001) and more readmissions (13.0% vs 0%, p <0.001). Adverse events after a mean follow-up period of 19.8 months were recurrences (3.7%), cardiac tamponade (<2%), but no cases of constriction. In conclusion, despite advances in cardiac surgery techniques, PPS is a common postoperative complication, generally occurring in the first 3 months after surgery. Severe complications are rare, but the syndrome is responsible for hospital stay prolongation and readmissions. Female gender and pleura incision are risk factors for PPS.

COlchicine for the Prevention of the Post-pericardiotomy Syndrome (COPPS): a multicentre, randomized, double-blind, placebo-controlled trial.

AIMS: No drug has been proven efficacious to prevent the post-pericardiotomy syndrome (PPS), but colchicine seems safe and effective for the treatment and prevention of pericarditis. The aim of the COlchicine for the Prevention of the Post-pericardiotomy Syndrome (COPPS) trial is to test the efficacy and safety of colchicine for the primary prevention of the PPS. METHODS AND RESULTS: The COPPS study is a multicentre, double-blind, randomized trial. On the third post-operative day, 360 patients (mean age 65.7 ± 12.3 years, 66% males), 180 in each treatment arm, were randomized to receive placebo or colchicine (1.0 mg twice daily for the first day followed by a maintenance dose of 0.5 mg twice daily for 1 month in patients ≥70 kg, and halved doses for patients <70 kg or intolerant to the highest dose). The primary efficacy endpoint was the incidence of PPS at 12 months. Secondary endpoint was the combined rate of disease-related hospitalization, cardiac tamponade, constrictive pericarditis, and relapses. Baseline characteristics were well balanced between the study groups. Colchicine significantly reduced the incidence of the PPS at 12 months compared with placebo (respectively, 8.9 vs. 21.1%; P = 0.002; number needed to treat = 8). Colchicine also reduced the secondary endpoint (respectively, 0.6 vs. 5.0%; P = 0.024). The rate of side effects (mainly related to gastrointestinal intolerance) was similar in the colchicine and placebo groups (respectively, 8.9 vs. 5.0%; P = 0.212). CONCLUSION: Colchicine is safe and efficacious in the prevention of the PPS and its related complications and may halve the risk of developing the syndrome following cardiac surgery. ClinicalTrials.gov number, NCT00128427.