Colchicine for Prevention of Postpericardiotomy Syndrome and Postoperative Atrial Fibrillation

Abstract

MD; for the COPPS-2 Investigators IMPORTANCE Postpericardiotomy syndrome, postoperative atrial fibrillation (AF), and postop-erative 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 gastro-intestinal adverse effects reduced the potential benefits of colchicine in this setting.

2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS

“…Inne metody leczenia również oceniano w małych próbach klinicznych generujących nowe hipotezy badawcze, ale nie wykazano jednoznacznie ich korzystnych efektów. Do ocenianych metod należało stosowanie magnezu [925,935,936], wielonienasyconych kwasów tłuszczowych z grupy omega-3 [937][938][939][940][941][942][943][944][945], kolchicyny [946] i glikokortykosteroidów [947,948], a także wycięcie tylnej części osierdzia [949]. Pooperacyjna stymulacja dwuprzedsionkowa narzuconym szybkim rytmem (overdrive) nie znalazła powszechnego zastosowania mimo pewnych danych wskazujących na jej profilaktyczny efekt [925,950].…”

2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS

“…934 Other therapies have also been studied in small, hypothesis-generating trials, but have not demonstrated clear beneficial effects. These include magnesium, 925,935,936 n-3 polyunsaturated fatty acids, 937 -945 colchicine, 946 corticosteroids, 947,948 and posterior pericardectomy. 949 Post-operative overdrive biatrial pacing has not gained widespread use despite some suggestion of prophylactic effects.…”

Defining the major health modifiers causing atrial fibrillation: a roadmap to underpin personalized prevention and treatment

“…Experimental and observational clinical data supported reninangiotensin-aldosterone blockers in AF prevention schemes 28,29 , but subsequent large randomized trials did not demonstrate a clinical benefit in patients without an established indication for these substances 30,31 . Drugs with anti-inflammatory and antioxidative properties that were tested for the prevention of AF in several settings showed mixed outcomes 23,[32][33][34][35] . Finding markers for the major disease mechanisms -or 'health modifiers' -causing AF in a given patient would enable some of these treatment modalities to be used successfully.…”