31 Aug COPPS-2 Evaluates Colchicine Pre-Cardiac Surgery To Prevent AFib and Effusions

MedicalResearch.com Interview with:
Massimo Imazio on behalf of the COPPS-2 Investigators
Massimo Imazio. MD, FESC
Dipartimento di Cardiologia/Cardiology Department
Maria Vittoria Hospital and University of Torino
Torino, Italia

Medical Research: What is the background for this investigation?

Dr. Imazio: Post-pericardiotomy syndrome, post-operative atrial fibrillation (AF), and post-operative effusions may be responsible for increased morbidity and healthcare costs after cardiac surgery. Postoperative use of colchicine prevented these complications in a single trial (the COPPS trial published on EHJ in 2010).

Here all events occurred within 3 months and colchicine was given after cardiac surgery starting from postoperative day 3 for 1 month. However most postoperative AF events are reported in the first 3 days and thus pre-treatment with colchicine may give better outcomes. Thus we performed the COPPS-2 giving colchicine 48 to 72 hours before surgery for 1 month without a loading dose and weight adjusted doses (i.e. 0.5 mg twice daily for patients >70kg or 0.5 mg once for patients <70Kg) in order to improve patients compliance.The Colchicine for Prevention of the Post-pericardiotomy Syndrome and post-operative atrial fibrillation (COPPS-2 trial) is an investigator-initiated, double-blind, placebo-controlled, randomized clinical trial. A total of 360 consecutive candidates for cardiac surgery, 180 for each arm, were enrolled in 11 Italian centers between March 2012 and March 2014. Main exclusion criteria were absence of sinus rhythm at enrollment, cardiac transplantation, and contraindications to .

Medical Research: What are the main findings of the study?

Dr. Imazio: At enrollment, mean age of the trial participants was 67.5±10.6 years, 69% were men, and 36% had planned valvular surgery. The primary end point occurred in 35 (19.4%) patients assigned to colchicine and in 53 (29.4%) assigned to placebo (absolute difference 10.0% 95%CI 1.1-18.7%, NNT=10). None of the secondary end points (incidence of post-operative AF and post-operative effusions) were significantly different between placebo and colchicine at the intention-to-treat analysis, except for a post-operative AF which was recorded in 61 (41.2%) patients assigned to placebo and 38 (27.0%) assigned to colchicine (absolute difference 14.3% 95%CI 3.3-24.7, NNT=7) at the pre-specified on-treatment analysis. Adverse events occurred in 21 (11.7%) patients for placebo group vs. 36 (20.0%) for colchicine (absolute difference 8.3% 95%CI 0.76-15.9%, NNH=12), but discontinuation rates were similar. No serious adverse events were observed.

Medical Research: Were any of the findings unexpected?

Dr. Imazio: Patients on colchicine treatment had more frequent side effects, especially gastrointestinal intolerance generally leading to drug withdrawal. About 20% of all patients enrolled in the trial experienced drug discontinuation and this relatively high rate may have affected the overall efficacy of the drug, especially for post-operative AF prevention.

Medical Research: What should clinicians and patients take away from your report?

Dr. Imazio: The high rate of side effects is a reason for concern and suggests that the drug should be considered only in well-selected patients; a longer pre-treatment time or initiation 2 to 3 days after surgery may reduce the occurrence of side effects and improve the compliance of patients as reported in the COPPS trial.However, considering the overall good prognosis of the post-pericardiotomy syndrome reported in the trial, its pre-operative prevention may be unnecessary in the perioperative phase because of the high rate of side effects. Early prevention after cardiac surgery or early specific treatment of the syndrome seems to warrant better tolerability and similar or better outcomes.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Imazio: In the COPPS-2 colchicine failed to reduce the incidence of post-operative AF in the intention-to-treat analysis; the high frequency of side effects and drug discontinuation were probably major causes since the pre-specified on-treatment analysis documented a significant reduction of the arrhythmia indicating that colchicine reduced the incidence of post-operative AF in patients who tolerated the drug. Ongoing studies will better clarify the potential of this drug using lower doses (i.e. 0.5 to 0.6 mg once daily) that may be better tolerated as well as a possible longer pre-treatment time.

Citation:

Last Updated on August 31, 2014 by Marie Benz MD FAAD