November 16, 2011

November 16, 2011 (Orlando, Florida) — New data from the Colchicine for the Prevention of the Postpericardiotomy Syndrome (COPPS) trial show that colchicine almost halves the incidence of postoperative atrial fibrillation in patients undergoing cardiac surgery [1]. The results were presented during a late-breaking clinical-trial session here at the American Heart Association 2011 Scientific Sessions by Dr Massimo Imazio (Maria Vittoria Hospital, Turin, Italy), and published simultaneously in Circulation.

Dr Massimo Imazio

Colchicine "as anti-inflammatory therapy appears to be an inexpensive and safe means to reduce the incidence of postoperative AF and hospitalization length," said Imazio during a press conference. However, he told heartwire : "I don't recommend the routine use of colchicine for the prevention of postoperative AF on the basis of a single trial. We need further multicenter trials to confirm this."

Study discussant Dr Nancy Nussmeier (SUNY Upstate Medical University, Syracuse, NY), an anesthesiologist, agreed, as did cardiac surgeon Dr Robert Higgins (Ohio State University, Columbus).

Higgins commented: "We see AF in 30% to 40% of our patients, and so any therapy that might have a beneficial effect in terms of the incidence or the management of that disease would be helpful, and I was compelled by the data." But he added that colchicine hadn't previously been tested in the cardiac-surgery patient, so it will be necessary to learn more about the drug in this patient group.

45.5% Reduction in Postop AF, Plus Shorter Hospital Stay

Colchicine is an anti-inflammatory drug that has been used for centuries for the treatment of gout, although it has only recently been approved for that use in the US, in 2006. It is also used to treat familial Mediterranean fever.

I don't recommend the routine use of colchicine for the prevention of postoperative AF on the basis of a single trial. We need further multicenter trials to confirm this.

In the COPPS study, reported at the European Society of Cardiology meeting last year, 360 cardiac-surgery patients were randomized to placebo or colchicine 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 focus of the study was to examine colchicine for the primary prevention of postpericardiotomy syndrome (PPS). Imazio stressed that colchicine is not registered for the prevention of pericarditis in North America or Europe and therefore this use is off-label.

The AF substudy of COPPS was prespecified to look at the occurrence of postoperative AF from the third postop day until one month after surgery, he noted. For this reason, 13 patients from the placebo group and 11 from the colchicine arm were excluded from the analysis because of AF occurring prior to day three.

Patients on colchicine had a significantly reduced incidence of postoperative AF between days 3 and 30, with a relative risk reduction of 45.5%, compared with those taking placebo (p=0.021). Colchicine use was also associated with a shorter in-hospital stay. But there was no difference in death or stroke rates between the two groups.

Adverse events were similar between the groups, with the exception of a trend toward more gastrointestinal side effects, primarily diarrhea, in the colchicine patients.

COPPS POAF Study Results

Event Placebo (n=167) Colchicine (n=169) p Relative risk reduction %
Postoperative AF* (%) 22.0 12.0 0.021 45.5
Cardiac surgery stay (days) 10.3 9.4 0.040  
Death or stroke, n (%) 2 (1.2) 2 (1.2) 0.616  
Gastrointestinal side effects 7 (4.2) 16 (9.5) 0.082  

*Primary end point

Post-Op AF Peaks on Days Two to Three, So More Work Needed

In an editorial accompanying the publication of Imazio's results in Circulation [2], Dr David R Van Wagoner (Cleveland Clinic, OH) says: "These results are promising and suggest that colchicine may be useful in the prevention of postoperative AF."

But one of the caveats is that the peak incidence of AF occurs on postoperative days 2 to 3, Wagoner points out. In fact, in COPPS, 43% of the AF episodes documented occurred before the onset of colchicine treatment.

"It is unclear whether colchicine would be equally effective in suppressing the earlier episodes of AF," he notes.

Imazio explained that because colchicine is an oral drug, which is difficult to administer in the immediate postoperative period, the decision was made to start therapy on day 3 in COPPS, the primary purpose of which was to prevent PPS.

He and his colleagues are now planning the COPPS 2 study, in which colchicine will be given starting 24 hours before surgery to examine its effects on PPS, postoperative AF, and effusions. Solutions of colchicine may also be employed in this trial, in addition to the oral drug, Imazio noted.

In her discussion, Nussmeier said this COPPS substudy is the first trial to show evidence of colchicine efficacy for the specific prevention of postoperative AF and that colchicine is therefore potentially a cheap, effective, and relatively safe option for this indication and for reducing the incidence of PPS.

She also urged further studies to look at earlier administration of the drug and said she would like to see larger multicenter trials confirming the efficacy of colchicine in these indications in other ethnic groups, as COPPS was primarily performed in whites.

Imazio and coauthors report that they have no conflicts of interest.