Colchicine in Cardiac Surgery: The COCS Randomized Clinical Trial

Abstract

Background. In patients who underwent cardiac surgery, first-time postoperative atrial fibrillation (POAF) is associated with increased incidence of hospital-acquired complications and mortality. Systemic inflammation is one of confirmed triggers of its development. The anti-inflammatory properties of colchicine can be effective for the POAF prevention. However, the results of several studies were questionable and required further investigation. Hence, we aimed to evaluate the effectiveness of low-dose short-term colchicine administration for POAF prevention in patients after the open-heart surgery. This double-blind randomized placebo-controlled trial included 267 patients, but 27 of them dropped out in the course of the study. Study subjects received the test drug on the day before the surgery and on postoperative days 2, 3, 4 and 5. The rhythm control was conducted immediately after the operation and until the discharge from the hospital. The final analysis included 240 study subjects: 113 in the colchicine group and 127 in the placebo group. POAF was observed in 21 (18.6%) patients of the colchicine group vs. 39 (30.7%) control patients (OR 0.515; 95% Cl 0.281–0.943; p = 0.029). We observed no statistically significant differences between the patient groups in the secondary endpoints of the study (hospital mortality, respiratory failure, stroke, bleeding, etc.). For other parameters characterizing the severity of inflammation (pericardial effusion, pleural effusion, WBC count, neutrophil count), there were statistically significant differences between the groups in the early postoperative period (days 3 and 5). Also, statistically significant differences between the groups in the frequency of adverse events were revealed: the incidence of diarrhea in the colchicine group was 25.7% vs. 11.8% in the placebo group (OR 2.578; 95% Cl 1.300–5.111; p = 0.005); for abdominal pain, incidence values were 7% vs. 1.6%, correspondingly (OR 4.762; 95% Cl 1.010–22.91; p = 0.028). Thus, there were statistically significant differences between groups in the primary endpoint, thereby confirming the effectiveness of short-term colchicine use for the POAF prevention after coronary artery bypass grafting and/or aortic valve replacement. Also, we detected statistically significant differences between groups in the frequency of side effects to colchicine: diarrhea and abdominal pain were more common in the colchicine group. This clinical trial is registered with ClinicalTrials database under a unique identifier: NCT04224545.

The Effect of Colchicine on Atrial Fibrillation: A Systematic Review and Meta-Analysis

“…Patients were monitored until discharge from the hospital for POAF. The colchicine group developed POAF in 18.6% of cases, while 30.7% developed it in the control group (OR 0.515; 95% CI 0.281-0.943; p=0.029) [19], thus confirming the effectiveness of colchicine in preventing POAF after cardiac surgery/aortic valve replacement.…”

“…A review article by Deftereos et al in 2019 [40] concluded that colchicine might have a preventive role in the development of AF after cardiac surgery or catheter ablation for PVI. Our metaanalysis includes the COCS trial [19], which was not included in the previous studies mentioned above. In addition, our meta-analysis includes four different sub-analyses, each analyzed separately rather than clubbing them together so that the results can be extrapolated correctly to the appropriate sub-group.…”

“…The 2022 COCS trial study by Shvartz et al [19] is one of the latest randomized controlled trials investigating the relationship between colchicine and AF. Patients undergoing cardiac surgery or aortic valve replacement were randomized to receive either 1 mg of colchicine or placebo 24 hours before surgery and on days two, three, four, and five.…”

Atrial fibrillation in vascular surgery: a systematic review and meta-analysis on prevalence, incidence and outcome implications

“…Nevertheless, the real weight and impact of AF in patients with arteriopathies undergoing vascular procedures or vascular surgery interventions is still unknown in terms of prevalence of a history of AF, incidence of POAF and implications for outcome. Indeed, while AF after cardiac surgery has been the object of many analyses and studies, [9][10][11][12][13][14] and AF after general or orthopedic surgery has recently attracted some interest, 3,6,15 very limited data are available on AF and vascular surgery.…”

New Perspectives on Risk Stratification and Treatment in Patients with Atrial Fibrillation: An Analysis of Recent Contributions on the Journal of Cardiovascular Disease and Development

“…Regarding the prevention strategy of AF in the postoperative setting, Nomani and colleagues [ 69 ] summarized recent evidence of several RCTs and meta-analyses highlighting the possible efficacy of statins in POAF prevention, especially for atorvastatin. In addition, the Colchicine in Cardiac Surgery randomized clinical trial demonstrated the efficacy of short-term colchicine intake in preventing POAF after coronary artery bypass graft and/or aortic valvular replacement [ 70 ].…”