BARCELONA, Spain - Saturday 30 August: Patients who took the anti-inflammatory drug colchicine just before cardiac surgery had a significantly lower risk of developing a common complication called post-pericardiotomy syndrome (PPS), according to a new study presented at the ESC 2014 Congress today.
But the drug's side-effects might be more trouble than its worth.
Results of the Colchicine for Prevention of the Post-pericardiotomy Syndrome and post-operative atrial fibrillation (COPPS-2) trial were presented as a Hot Line at the congress and published simultaneously in the Journal of the American Medical Association.
"There was a high rate of gastrointestinal side effects in the study and this is a concern," noted study investigator Massimo Imazio, MD, from Maria Vittoria Hospital in Torino, Italy. "It suggests that the drug should be considered only in well-selected patients."
"What surprised me was the overall good prognosis of PPS that we observed in the trial, suggesting that perhaps pre-surgical prevention may be unnecessary altogether," he said. "Instead, early prevention immediately after cardiac surgery or early treatment of PPS seems preferable, since it appears to be better tolerated and have similar or better outcomes."
PPS is a post-surgical reaction involving fever and inflammation around the heart and lungs. About one third of cardiac patients are affected by either PPS, post-operative atrial fibrillation (heart rhythm problems) or post-operative pericardial and/or pleural effusions (fluid around the heart) with the potential for prolonged hospital stays, increased readmissions, and possibly the need for invasive interventions.
COPPS-2, a multicenter, double-blind, placebo-controlled, randomised clinical trial, looked at the potential of pre-operative administration of colchicine to prevent these three conditions in 360 consecutive cardiac surgery candidates from 11 centers in Italy.
Patients (mean age 67 years, 69% male) were randomised to start placebo (n=180) or colchicine (n=180) between 48 and 72 hours before surgery and continue for one month after surgery.
Dosing was 0.5 mg twice daily for patients weighing at least 70 kg, or once daily for patients weighing less.
The main aim of the study was to determine the rate of PPS in the first three months after surgery, with secondary assessments of post-operative atrial fibrillation and effusions.
The study found that PPS was significantly less common in the colchicine group compared to the placebo group (19.4% vs. 29.4%; p=0.030; relative risk [RR] 0.66), but medication did not reduce the incidence of the post-operative atrial fibrillation or post-operative effusions.
However when drug withdrawals due to gastrointestinal side-effects were removed from the analysis patients who could tolerate the drug had a lower rate of post-operative atrial fibrillation compared to those on placebo (RR 0.65; p=0.012).
Adverse event rates were higher in the colchicine group (20.0% vs. 11.7%; RR 1.89; p=0.034), largely as a result of increased gastrointestinal intolerance (RR 2.17; p=0.020).
However overall rates of study drug discontinuation were similar and relatively high for both groups (about 20%), with no serious adverse events observed.
COPPS-2 comes on the heels of the first COPPS trial which showed a similar benefit of colchicine, but when given after, rather than before cardiac surgery. The big difference between the two trials is that the first trial showed no increase in adverse events compared to placebo.
"We observed more side effects in COPPS-2, probably because patients are more susceptible in the perioperative period, when the common use of antibiotics and proton pump inhibitors greatly increases the risk of gastrointestinal side effects," said Professor Imazio.
"We hypothesised that in COPPS-2, an earlier start for the drug, with more gradual dosing might improve both efficacy and compliance, but instead it just increased gastrointestinal side effects."
At present, colchicine is not approved for the prevention of the PPS in North America or Europe, and its use is off-label for this indication. It is currently approved for the treatment of gout and Familial Mediterranean Fever.