By Michael H. Crawford, MD

Professor of Medicine, Chief of Clinical Cardiology University of California, San Francisco

Dr. Crawford reports no financial relationships relevant to this field of study. This article originally appeared in the September 2014 issue of Clinical Cardiology Alert.

SOURCE: Imazio M, et al. Efficacy and safety of colchicine for treatment of multiple recurrences of pericarditis (CORP-2): A multicenter, double-blind, placebo-controlled, randomised trial. Lancet 2014;383:2232-2237.  

Although colchicine has been shown to be effective for the treatment of acute pericarditis and first recurrences, little information exists about its use in patients with multiple recurrences. Thus, Imazio et al reported on the results of the colchicine for recurrent pericarditis 2 (CORP-2) trial. CORP-2 was a randomized, controlled trial performed at four general hospitals in Italy. Recurrent pericarditis was defined as another episode after a 6-week or more symptom-free interval. Recurrence was diagnosed as recurrent pain and at least one of the following: a pericardial friction rub, typical ECG changes, pericardial effusion on echocardiography, or elevated inflammatory biomarkers (white blood cell count, erythrocyte sedimentation rate or C-reactive protein concentration). Two or more recurrences of pericarditis caused by idiopathic/viral, post-cardiac injury, or connective tissue disease were required for enrollment. Patients with purulent pericarditis, myopericarditis, or a contraindication to colchicine (e.g., liver disease) were excluded. Colchicine was given to half the subjects (randomized) at a dose of 0.5 or 1.0 mg daily for 6 months without a loading dose. Recurrences were also treated with non-steroidal anti-inflammatory drugs (NSAIDs) as needed. Corticosteroids were given to those already on them or those who could not take NSAIDs. All patients received a proton pump inhibitor. The primary endpoint was recurrent pericarditis during at least 18 months of follow-up.

Of the 260 patients screened, a total of 240 patients were enrolled, 120 in each group, over about 6 years. No one was lost to follow-up. Adherence to both treatments was 95%. Pericarditis recurred in 22% of the colchicine group vs 43% of the placebo group (relative risk, 0.49; 95% confidence interval [CI], 0.24-0.65; P < 0.001; number needed to treat = 5). The Kaplan-Meier curves of event-free survival separated at 2 months and stayed separated for the 18-month minimum follow-up. Colchicine also significantly improved the following secondary endpoints: the frequency of symptom persistence, the number of recurrences, hospital admissions, and recurrences within 1 week. In a multivariate analysis, pericardial effusion at presentation was the only independent risk factor for multiple recurrences (odds ratio, 3.1; 95% CI, 1.7-5.8; P = 0.0001). Adverse effects occurred in 12% of the colchicine group and 8% in the placebo group (P = NS). Gastrointestinal side effects were most common and occurred at the same frequency in both groups (7.5%). The authors concluded that colchicine added to conventional NSAID therapy reduces the frequency of pericarditis recurrence in patients with two or more recurrences.

COMMENTARY

This study completes the Imazio et al trilogy on the treatment of pericarditis and suggests that colchicine is the drug of first choice for acute pericarditis, first recurrences, and multiple recurrences.1,2 In this study, its beneficial effects were not related to the type of underlying NSAID or corticosteroid therapy. It basically halves the rate of recurrent pericarditis in these challenging patients.

Why is colchicine so effective and conventional treatment not? The pathogenesis of recurrences is poorly understood, but most believe it is immune-mediated. Colchicine concentrates up to 16-fold in white blood cells and disrupts microtubules, even at the low does used in this trial. Often, multiple recurrent pericarditis patients are treated with more potent immune-suppressant drugs such as azathioprine, intravenous immunoglobulins, and interleukin antagonists. However, there is little evidence of their effectiveness. Also, they are expensive and have potentially worse adverse effects. Thus, this colchicine protocol is a welcome addition to the treatment of recurrent pericarditis patients.

For acute pericarditis, Imazio recommends a loading dose of 1 mg (1.2 U.S. formulation) every 12 hours for 1-2 days, then 0.5 mg (0.6 U.S. formulation) once a day for those < 70 kg, and 0.5 (0.6 U.S. formulation) twice a day for those > 70 kg for 3 months. Recurrent pericarditis is treated without a loading dose in the same fashion for 6 months. This only applies to immune-mediated pericarditis — e.g., viral, idiopathic or post pericardiotomy, not bacterial, neoplastic or myopericarditis. Also excluded from these studies were children and pregnant or lactating women. Finally, the duration of therapy in these studies was arbitrary and we don’t know if shorter or longer durations would be equally or even more effective.

REFERENCES

  1. Imazio M, et al. N Engl J Med 2013;369:1522-1528.
  2. Imazio M, et al. Arch Intern Med 2005;165:1987-1991.