Colchicine Prevents Post-pericardiotomy Syndrome
Abstract & Commentary
By Andrew J. Boyle, MBBS, PhD
Source: Imazio M et al. Colchicine for the Prevention of the Post-pericardiotomy Syndrome (COPPS): A multicentre, randomized, double-blind, placebo-controlled trial. Eur Heart J. 2010;31:2749-2754.
Post-pericardiotomy syndrome (PPS) is relatively common after cardiac surgery, and can result in life-threatening events, such as cardiac tamponade, increased length of stay, readmission to hospital, and significant patient discomfort. There is currently no accepted strategy to prevent its occurrence. Colchicine has been demonstrated to effectively treat acute pericarditis, but its role in the prevention of PPS had not been fully elucidated. Imazio and colleagues, therefore, performed a multi-center, randomized, double-blind, placebo-controlled trial to test whether colchicine could prevent PPS.
The authors enrolled 360 consecutive adult patients who had undergone cardiac surgery and randomized them to receive either colchicine 1 mg twice daily for the first day followed by a maintenance dose of 0.5 mg twice daily in patients ≥ 70kg and 0.25 mg twice daily in those < 70kg (n = 180) vs. placebo (n = 180) starting on the third post-operative day. Exclusion criteria included patients with known liver or kidney disease, myopathy, blood dyscrasias, gastrointestinal disease, pregnancy, or lactation. PPS was diagnosed when two or more of the following five criteria were present: pleuritic chest pain, fever beyond the first post-operative week in the absence of infection, friction rub, pleural effusion, or a new or worsening pericardial effusion. The primary endpoint was the incidence of PPS at 12 months. Secondary endpoint was the combination of disease-related hospitalization, cardiac tamponade, constrictive pericarditis, and recurrent pericarditis.
Results: Baseline demographics were well-matched between the placebo and colchicine groups, with mean age 66 years and two-thirds of patients being male. Surgeries performed also were similar between groups, with the majority being coronary-artery bypass graft surgery and/or valvular surgery. Colchicine significantly reduced the incidence of post-pericardiotomy syndrome at 12 months (8.9% vs. 21.1%, respectively; p = 0.002). The majority (85%) of PPS events occurred in the first 30 days. Colchicine reduced the incidence of the combined secondary endpoint (0.6% vs. 5.0%; p = 0.024). The rates of side effects (8.9% vs. 5.0%; p = 0.21) and drug withdrawal (11.7% vs. 6.7%; p = 0.145) were similar with colchicine and placebo, respectively, although there was a numerical trend toward more side effects with colchicine. There were five fewer hospitalizations in the colchicine group. The authors conclude that 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.
In patients assigned to placebo, there was a 21.1% rate of PPS, and the most common presenting symptoms were pleural effusion, pericardial effusion, and chest pain. This may lead to significant patient morbidity. The reduction in the incidence of PPS with colchicine has the potential to improve the patients' experience following cardiac surgery, although there was no quality-of-life data reported. Colchicine is a cheap and relatively safe drug that has the potential to realize not only symptomatic benefits, but also significant cost savings by preventing readmissions; however, we are not presented with any cost-effectiveness analysis. In addition, we are not told how long the colchicine was continued, on average, in this study. Because 85% of the cases occurred in the first month, it would seem reasonable that a one-month course of colchicine following cardiac surgery may reduce the incidence of PPS and improve patients' experience.