Colchicine for Acute Pericarditis
Abstract & Commentary
By Michael H. Crawford, MD, Dr. Crawford is a Professor of Medicine, and Chief of Clinical Cardiology, at the University of California, San Francisco; and he is the Editor of Clinical Cardiology Alert.
Synopsis: Colchicine added to conventional therapy for acute pericarditis reduced the recurrence rate and corticosteroids increased it.
Source: Imazio M, et al. Colchicine in Addition to Conventional Therapy for Acute Pericarditis: Results of the COlchicine for Acute PEricarditis (COPE) Trial. Circulation. 2005:112:2012-2016.
Colchicine is an anti-inflammatory agent that has been used successfully to treat recurrent pericarditis. Imazio and colleagues from Italy, hypothesized that if colchicine was started during acute pericarditis, it may reduce recurrences. They studied 120 patients with a first episode of acute pericarditis. The only exclusion criteria were infective and neoplastic causes and contraindications to colchicine therapy. Acute pericarditis was diagnosed by 2 of the following: typical chest pain, friction rub, or characteristic ECG changes. The patients were randomly assigned to conventional therapy with high-dose aspirin (800 mg po 6-8 hours for 7-10 days then tapering off over 1 month) or aspirin plus colchicine, 1-2 mg the first day followed by 0.5-1.0 mg daily for 3 months. Corticosteroids were only used in those [who were] aspirin intolerant. The primary end point was recurrent pericarditis, defined as pain plus evidence of pericardial inflammation (blood tests, ECG, echocardiogram).
Results: Over a mean follow-up of 24 months, a higher recurrence rate was observed in the aspirin-alone group vs the colchicine group (33% vs 12%; P = .009). Almost all recurrences occurred within 18 months. Colchicine-treated patients had a longer symptom-free interval (23 vs 17 months; P = .007). Corticosteroids were given to 16% of the patients; in this subgroup, recurrence rates were 87% in the corticosteroid group vs 11% in the corticosteroid plus colchicine group (P < .001). Multivariate analysis confirms that early steroid use increased the recurrent rate significantly, and colchicine use lowered it. Overall adverse effects were mild: 8% had diarrhea on colchicine and 7% had GI side effects on aspirin (P = NS). Imazio et al concluded that colchicine added to conventional therapy for acute pericarditis reduced the recurrence rate and corticosteroids increased it.
This paper advances the concept that colchicine should be standard therapy along with NSAIDs, such as aspirin, for acute pericarditis and, that after the first few weeks, only the colchicine should be continued for 3 months. It hastened the resolution of symptoms, and deceased recurrences of 2 years, compared to early aspirin therapy alone. There is a good biologic rationale for the drug since it affects the secretory function of leukocytes, which should reduce inflammation. The drug dose was weight adjusted, but GI side effects still occurred in about 8% of those treated with colchicine. This may limit therapy. Although used for years to treat recurrent pericarditis, this study recommends it for early treatment and late prophylaxis against recurrence. Predictably steroids increased the number of recurrences.
It is tempting to change our practice based upon this study, but it had several weaknesses. It was open label, so treatment biases could have occurred. The primary end point of pericarditis recurrence required symptoms which are subjective. Theoretically, acute pericarditis is viral, and etiology and recurrences are due to autoimmune phenomena. They excluded infective and neoplastic causes, but included patients with autoimmune diseases. How much these later patients would have affected the early beneficial effect is unclear. Finally, colchicine therapy alone was not studied, and only one duration of therapy was tested.