Colchicine Postablation Reduces Early AF Recurrences

October 04, 2012

October 3, 2012 (Baltimore, Maryland) — The administration of colchicine in patients who underwent pulmonary vein isolation helps to prevent early recurrences of atrial fibrillation, research shows [1]. The reduction in event recurrences appears to be mediated through a reduction in inflammation following the radiofrequency catheter-ablation procedure, with investigators showing significant reductions in inflammatory mediators such as interleukin-6 (IL-6) and C-reactive protein (CRP).

"The idea of fighting inflammation after ablation treatment for atrial fibrillation is not a novelty," lead investigator Dr Georgios Giannopoulos (Athens General Hospital, Greece) told heartwire . "However, there is the question of how to reduce inflammation. Corticosteroids and [nonsteroidal anti-inflammatory drugs] NSAIDs are out of the question for prolonged use. Colchicine, on the other hand--a low-cost medicine that has been around for more than 2000 years--possesses a unique combination of features: anti-inflammatory action, antiproliferative action, and no adverse effects on the cardiovascular system, at least in the dose range used in this study."

Given the potent anti-inflammatory action of colchicine and that it can be administered without serious cardiovascular adverse effects for a relatively prolonged time period, the researchers assessed the safety and efficacy of the agent in the setting of atrial-fibrillation ablation. In the study, published online October 3, 2012 in the Journal of the American College of Cardiology, the researchers randomized 81 patients with paroxysmal atrial fibrillation to a three-month course of colchicine 0.5 mg twice daily and 80 patients to placebo.

Reduces Early AF Recurrences 62%

After three months of treatment, atrial-fibrillation recurrence was observed in 33.5% of patients treated with placebo and 16% of patients treated with colchicine (odds ratio 0.38; 95% CI 0.18–0.80). The number needed to treat to prevent one recurrence was 5.6. The mean recurrence-free time in the placebo-treated patients was 68.9 days, compared with 82.2 days in the colchicine-treated patients.

In addition to reducing the risk of atrial-fibrillation recurrence, colchicine significantly reduced CRP and IL-6 levels. Measured on day 4 of treatment, CRP and IL-6 levels declined 1.18 mg/L and 0.50 pg/mL, respectively, from baseline in the colchicine-treated patients. Comparatively, the mean reduction in CRP and IL-6 in the placebo arm was 0.46 mg/L and 0.10 pg/mL, respectively.

To heartwire , Giannopoulos noted that previous studies have shown that proinflammatory mediators increase following atrial-fibrillation ablation and that these levels are independently associated with an increased risk of arrhythmia recurrences. One study also showed that the administration of corticosteroids following ablation reduced immediate atrial fibrillation by 77%.

"In general, the association between inflammation biomarkers and atrial fibrillation is well-established and supported by numerous studies," he said. "However, the exact mechanism of this link has not been elucidated. It has been speculated that inflammation alters the conduction properties of atrial myocytes and is associated with cell degeneration and apoptosis, resulting in higher likelihood of atrial fibrillation. It should be noted that in our study colchicine led to a substantial reduction in the measured inflammatory markers, and this reduction was an independent predictor of freedom from early atrial fibrillation recurrence."

More Work Needs to Be Done

The most commonly reported side effect with colchicine was gastrointestinal, mainly diarrhea and nausea. In an editorial accompanying the study [2], Drs Gregory Marcus and Jonathan Hsu (University of California, San Diego) state that a few more steps are needed before colchicine can be used regularly in clinical practice. While the dose and duration of treatment are not firmly established, they warn that because the primary rationale for catheter ablation of atrial fibrillation is to improve quality of life, physicians should not replace one problem, atrial fibrillation, with another, gastrointestinal upset. One patient stopped treatment because of an increase in liver enzymes.

"It is possible that a shorter duration would suffice," suggest Marcus and Hsu. "Discontinuing colchicine for intolerance or adverse reaction before one month of therapy was rare, suggesting that one month may be a reasonable duration to maximize tolerance."

And of course, long-term studies are needed to determine whether the reduction in short-term atrial-fibrillation recurrence translates into long-term success. To heartwire , Giannopoulos said this study is currently ongoing. The researchers are extending the three-month trial to see whether treatment reduced the rate of recurrence at 12 months. If that pans out, it would be worthwhile to conduct a large-scale clinical trial assessing hard clinical end points, as long as funding can be found, he said.