PARIS – In patients with a first recurrence of pericarditis, adding low-dose colchicine to standard therapy halved the risk of subsequent episodes of pericarditis.
Among 120 patients with a first recurrence of pericarditis in the Study of Colchicine to Treat and Prevent Recurrent Pericarditis (CORP) trial, the rate at 18 months of another recurrence was 24% with colchicine and standard therapy and 55% with placebo and standard therapy (P value less than .001).
The relative risk reduction associated with adjuvant colchicine was 56% and the number needed to treat to prevent one recurrence was three, Dr. Massimo Imazio reported at the annual congress of the European Society of Cardiology.
Colchicine (Colcrys) has been used for years to treat gout, and is the first drug to be shown in a double-blind, randomized placebo-controlled trial to prevent recurrent pericarditis.
"Following an initial episode of recurrent pericarditis, colchicine, as an adjunct to anti-inflammatory therapy, appears to be an inexpensive and safe means to hasten symptom resolution, improving remission rates by one week, and to reduce further recurrences during follow-up," said Dr. Imazio of the Maria Vittoria Hospital in Turin, Italy.
Invited discussant Dr. Andre Keren, director of the Heart Failure and Heart Muscle Disease Center at the Heart Institute at Hadassah University Hospital in Jerusalem, described CORP as a well-designed and carefully performed trial. Its results strongly support the use of low-dose colchicine as a safe, well-tolerated, and effective first-line adjuvant to standard treatment in patients with recurrent pericarditis.
"I really believe that the time has arrived that colchicine should be more freely used," he said.
Both Dr. Imazio and Dr. Keren observed that the results may not be applicable to all patients with pericarditis since the trial excluded those patients with neoplastic or bacterial etiologies for their pericarditis as well as patients with multiple recurrences of pericarditis.
In addition, the drug’s "remarkable" safety and tolerability profile might have been influenced by careful patient selection and the low doses employed in the study, Dr. Keren said.
Based on nonrandomized observational findings and expert opinion, the European Society of Cardiology guidelines recommend colchicine 2 mg/day for 1 to 2 days, followed by a maintenance dose of 1 mg/day for the treatment of recurrent pericarditis.
The CORP investigators randomized patients from four Italian centers to conventional therapy plus placebo or colchicine for 6 months at the recommended doses for patients weighing at least 70 kg, but reduced the initial dose to 1 mg/day and the maintenance dose to 0.5 mg/day for those weighing less than 70 kg.
Conventional therapy was aspirin 800 mg-1,000 mg or ibuprofen 600 mg every 8 hours for 7-10 days, with the second choice being prednisone 0.2-0.5 mg/kg of body weight per day for 4 weeks and then gradually tapered.
Dr. Keren pointed out that the dose as well as the frequency of corticosteroids was lower in CORP than the researchers’ earlier CORE trial, in which prednisone was dosed at 1.0-1.5 mg/kg of body weight per day for 4 weeks, and 35% of patients had received steroids during the initial episode of pericarditis. In contrast, only 10% of placebo and 8% of colchicine patients in CORP had previously received corticosteroids.
"This might also reflect, in my view, a change in our perception that steroids can actually be deleterious in decreasing the recurrence rate," Dr. Keren said.
Symptom persistence at 72 hours was significantly lower in the colchicine group than in the placebo group (23% vs. 53%, P = .001), as was the rate of remission at 1 week (48% vs. 82%, P less than .001), Dr. Imazio said.
The mean number of recurrences was significantly lower in the colchicine-treated group than in the placebo group (0.1 vs. 1.0), and the time to first recurrence was also significantly longer at 2.5 months vs. 1 month (both P less than .001).
No significant differences were observed between the two groups in rates of readmission (5% vs. 13%), tamponade (0% vs. 2%), or constriction (0% both).
Gastrointestinal intolerance was the most common side effect, reported in four colchicine- and five placebo-treated patients. No severe side effects were observed in either group. Treatment discontinuation occurred in five colchicine and four placebo patients, Dr. Imazio said.
Full results of CORP are available online in the Annals of Internal Medicine (Ann. Intern. Med. 2011 Aug. 28 [Epub ahead of print]).
Dr. Imazio and his coauthors report no study sponsorship or conflicts. Dr. Keren reports no disclosures.