Colchicine in Acute Pericarditis

ABSTRACT & COMMENTARY

By Andrew J. Boyle, MBBS, PhD

Assistant Professor of Medicine, Interventional Cardiology, University of California, San Francisco

Dr. Boyle reports no financial relationships relevant to this field of study.

This article originally appeared in the December 2013 issue of Clinical Cardiology Alert. It was edited by Michael H. Crawford, MD, Professor of Medicine, Chief of Clinical Cardiology, University of California, San Francisco, and peer reviewed by Ethan Weiss, MD, Assistant Professor of Medicine, Division of Cardiology and CVRI, University of California, San Francisco. Dr. Crawford reports no financial relationships relevant to this field of study, and Dr. Weiss is a scientific advisory board member for Bionovo.

Source: Imazio M, et al. A randomized trial of colchicine for acute pericarditis. N Engl J Med 2013;369:1522-1528.

Colchicine is indicated for treatment of recurrent pericarditis. However, its role in acute pericarditis is less clear. Previous observational series and single-center, open-label studies have suggested a benefit in acute pericarditis, but this remains to be proven. Accordingly, Imazio and colleagues performed a randomized, placebo-controlled, multicenter study of usual care (aspirin, ibuprofen, or glucocorticoids) plus either colchicine or placebo in patients with acute pericarditis.

Patients ≥ 18 years of age presenting with their first episode of acute pericarditis were enrolled. They were considered to have acute pericarditis if they had at least two of the following four clinical features: typical chest pain (pleuritic and relieved by sitting forward), typical ECG changes, pericardial friction rub, or pericardial effusion on echocardiography. Patients with idiopathic, viral, post-cardiac injury or connective tissue disease-associated pericarditis were included. Exclusion criteria included the presence of myopericarditis, tuberculous, neoplastic or purulent pericarditis, significant liver or kidney disease (creatinine > 2.5 mg/dL), blood dyscrasias, myopathy, pregnancy, lactation, and inflammatory bowel disease. Colchicine or placebo were administered for at least 3 months. The dose of colchicine was 0.5 mg twice daily, or 0.5 mg once daily for those under 70 kg and those with side effects on 0.5 mg twice daily. Usual care was either aspirin 800 mg or ibuprofen 600 mg every 8 hours. Glucocorticoids were reserved for patients intolerant of aspirin or ibuprofen, and were tapered over 2 weeks. All patients also received proton pump inhibitors. All patients were followed for at least 18 months, and the primary endpoint was recurrent or incessant pericarditis. Recurrent pericarditis was defined as resolution of acute pericarditis for at least 6 weeks followed by another episode. Incessant pericarditis was defined as ongoing symptoms or a repeat episode with less than 6 weeks symptoms-free. Secondary endpoints were symptom persistence at 72 hours, remission within 1 week, number of recurrences, time to first recurrence, pericarditis-related hospitalization, cardiac tamponade, and constrictive pericarditis.

A total of 240 patients were randomized to colchicine (n = 120) or placebo (n = 120). Baseline demographics were similar between groups. The average age was 52 years, 61% were male, and the vast majority were idiopathic/viral in etiology (77%). Pericardial effusion was present in two-thirds. Usual care consisted of aspirin in approximately 80%, ibuprofen in 15%, and glucocorticoids in 5%. Adherence to the study drug was closely monitored and exceeded 95% in both groups. The primary outcome of recurrent or incessant pericarditis occurred in 17% of the colchicine group and 38% of the placebo group (relative risk 0.56; P < 0.001). The number needed to treat (NNT) to prevent one case of recurrent or incessant pericarditis was 4. The results were similar whether patients were treated with aspirin or ibuprofen. Patients treated with colchicine, compared to placebo, had lower rates of symptom persistence at 72 hours (19% vs 40%; P = 0.001), pericarditis-related hospitalization (5% vs 14%; P = 0.02), and number of recurrences per patient (0.21 vs 0.52; P = 0.001). Colchicine improved the rate of remission at 1 week (85% vs 58%; P < 0.001) and time to first recurrence (25 weeks vs 18 weeks; P < 0.001). Adverse event rates and drug discontinuation rates did not differ between groups (12% vs 10% and 12% vs 8%, respectively). The authors conclude that in patients with acute pericarditis, colchicine added to conventional anti-inflammatory therapy significantly reduced the rate of recurrent or incessant pericarditis.

COMMENTARY

Colchicine is an old drug that has an established role in recurrent pericarditis. Recently, it has been shown to prevent pericarditis after cardiac surgery and now in the current study, it has gained a place as treatment for the first attack of acute pericarditis. The rigorous trial design strengthens the conclusions made from this dataset. The study was an investigator-initiated, randomized, placebo-controlled, multicenter trial with all events adjudicated by a blinded clinical events committee. Interestingly, the majority of patients took aspirin as the anti-inflammatory of choice, which may reflect regional practice variations. The study did not address which anti-inflammatory is the best, allowing ibuprofen or aspirin at the treating physician's discretion. The major limitations to the use of colchicine in clinical practice are nausea and diarrhea. Interestingly, in this study, there were no differences in the rates of gastrointestinal upset or drug discontinuation compared to placebo. The dose reduction in patients who develop side effects (rather than cessation) and the lower dose in smaller patients are important in maintaining patients on their therapeutic regimen. This is a low-cost, well-tolerated treatment that can improve symptoms and reduce hospitalizations for pericarditis. This will be a welcome addition to standard anti-inflammatories in patients with their first attack of acute pericarditis.