Stockholm, Sweden - The first large-scale double-blind, placebo-controlled trial to test the efficacy of colchicine to prevent the development of postpericardiotomy syndrome (PPS) after heart surgery has shown that the drug is very effective, with only eight people needing to be treated to prevent one from developing the syndrome.
"Colchicine halves the risk of postpericardiotomy syndrome following cardiac surgery, and not only is it efficacious but it is safe," said lead author of the study, Dr Massimo Imazio (Maria Vittoria Hospital, Turin, Italy), who presented the findings at the European Society of Cardiology 2010 Congress today. The results were also published simultaneously in the European Heart Journal.
Discussant for the study, Dr Andre Keren (Hadassah University Hospital, Jerusalem, Israel), concurred. He said this was "a carefully performed trial in which colchicine proved an effective and safe treatment modality—it halved the risk of developing postpericardiotomy syndrome without major side effects, and I would like to congratulate the study authors."
Impressive reduction of primary end point with colchicine
Imazio explained that PPS is a relatively common and troublesome complication following cardiac surgery, occurring a few days to several weeks after the surgical operation in 10% to 40% of patients. PPS can have a difficult course and complicate the postoperative period with life-threatening events such as cardiac tamponade; moreover, it may prolong the hospital stay and increase management costs, he said. Treatment is based on aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs), with steroids being considered in the case of contraindications to or failure of NSAIDs. At present, no pharmacological strategies have been proven to be efficacious in the prevention of the syndrome, he noted. Anecdotal reports have suggested that colchicine may be useful for the treatment of patients with PPS, and it has also been proposed for the primary prevention of the condition on the basis of a preliminary report from Israel. However, this study was insufficiently powered to show a benefit of colchicine in this indication, Imazio explained. The new trial, Colchicine for the Prevention of the Postpericardiotomy Syndrome (COPPS), is the first prospective, randomized, multicenter trial to test colchicine for the primary prevention of PPS using intention-to-treat analysis, he added. In the study, 360 cardiac-surgery patients were randomized to colchicine or placebo on the third postoperative day, with those receiving the active drug taking 1.0 mg twice daily for the first day followed by a maintenance dose of 0.5 mg twice daily for one month in those >70 kg; doses were halved for those <70 kg or intolerant to the higher dose. The primary efficacy end point was the incidence of PPS at 12 months. The secondary end point was the combined rate of disease-related hospitalization, cardiac tamponade, constrictive pericarditis, and relapses. There was an "impressive" relative risk reduction with colchicine of 57.9% for the primary end point, Imazio said. Colchicine also significantly reduced the rate of the secondary end point, although Keren observed in his discussion that this was not as great a reduction as that seen with the primary end point.
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). The relative lack of side effects seen in this trial could be due to the fact that Imazio and colleagues used a much lower dose of colchicine, around a third of that used in the earlier preliminary Israeli trial, Keren said. In their paper, the Italian researchers say the exact mechanism of colchicine action is not fully understood. Most of the pharmacological effects of the drug on inflammation appear to be related to its capacity to disrupt microtubules, and by this mechanism, colchicine is able to inhibit various leukocyte functions, they note, adding that this effect is likely the most significant for the anti-inflammatory action.
Definition of PPS still problematic
Imazio added that the major limitation of the study relates to the definition of PPS, "because there is no general agreement on how to diagnose the syndrome," with the only published criteria having been proposed in the preliminary study from Israel.
"We adopted the same diagnostic criteria for PPS. They can be criticized and considered weak," he and his colleagues state in the paper. "Nevertheless, they represent the first attempt to have an objective approach to the diagnosis."
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