What is the Role of Colchicine in Recurrent Pericarditis?

March 14, 2009

99px-gray501.pngCommentary by Sabina Berezovskaya MD, PGY-3

Faculty Peer Reviewed

Up to 32% of patients with acute pericarditis will have a recurrent episode. Acute attacks are commonly precipitated by infections, malignancy, cardiac trauma, myocardial infection, or autoimmune disease. Recurrent pericarditis usually presents with symptoms akin to the acute attack, including chest pain, fever, pericardial rub, typical electrocardiographic findings (i.e. diffuse ST elevations and PR depressions), pericardial effusion and, infrequently, tamponade. The time to relapse after acute pericarditis usually occurs within 18 to 20 months; however some report recurrences after 15 years of remission (Fowler). Many experts believe that recurrent pericarditis is an autoimmune phenomenon, as evidenced by preferential increase of inflammatory cytokines in the pericardial fluid, elevated serum ESR and CRP, and responsiveness to steroid therapy. Others suggest that the prevalence of viral pericarditis is grossly underestimated. Two types of recurrences have been identified: the intermittent form, where a relapse occurs after an asymptomatic period of > 6 weeks after discontinuation of therapy, and the incessant form, where recurrence occurs <6 weeks of discontinuation of therapy. Current mainstay therapy includes nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen or aspirin, colchicine as an adjunct to NSAIDs or as monotherapy, systemic corticosteroids, which are used in refractory disease, and intrapericardial steroids. More aggressive measures, such as pericardiectomy, are reserved for very symptomatic, frequent, and refractory recurrences.

Efforts have been made to identify clinical markers that would predict recurrence of pericarditis. According to present data, the only known risk factors include initial response to NSAID therapy and the use of corticosteroids. In a study published in Journal of American College of Cardiology, Imazio et al. noted a higher recurrence rate and constriction in low risk patients who were unresponsive to aspirin therapy. In this study low risk group included patients without poor prognostic predictors, such as temp>38C, subacute onset, immunosuppression, trauma, oral anticoagulation, myopericarditis, significant pericardial effusion or cardiac tamponade. Further data on increase rate of recurrences in NSAIDs nonresponders requiring glucocorticoid therapy came from the Colchicine for Acute Pericarditis (COPE) trial. In this study corticosteroid use was found to be an independent risk factor for recurrent pericarditis (OR 4.30). In addition to being reserved to more resistant cases, the increased incidence of recurrence observed in patients on glucorticoid therapy has been linked to the potentiation of virally induced pericarditis by steroids.

More notably the outcomes of these trials suggest that colchicine use significantly reduced the recurrence of pericarditis. The COPE trial reported that addition of colchicine to standard therapy reduced recurrence rate by 3 fold at 18 months after the initial attack with number needed to treat of 5 and resulted in less symptoms within first 72 hours.  The use of colchicine in the treatment of pericarditis was extrapolated from the observation of the effectiveness of the drug in patients with Familial Mediterranean Fever (FMF). FMF is characterized by recurrent serositis, including pericarditis. Colchine is an alkaloid drug that decreases the inflammatory process by interfering with polymorphonuclear cells migration and phagocytosis by disrupting tubulin polymerization. This in turn prevents intracellular movement and secretion of proinflammatory substances resulting in less inflammation and its sequelae.

Further support for colchicine use in recurrent pericarditis comes from Colchicine as First-Choice Therapy for Recurrent Pericarditis: Results of the CORE (Colchicine for Recurrent pericaditis) Trial. This was a perspective, randomized, open-labeled study with the intention to treat analyses, designed to evaluate risks and benefits of colchicine therapy in recurrent pericarditis. A total of 84 patients with a first episode of recurrent pericarditis were randomized to aspirin alone ( 800 mg q6 or q8h for 7-10 days with tapering over 3-4 weeks) or aspirin plus colchicine (1-2 mg on 1st day and then 0.5-1 mg/d for 6 months). Prednisone was used when aspirin was contraindicated. After a 1682 patient-month follow up, a significantly lower rate of recurrence at 18 months was noted in the treatment group (24% v. 51 %) with the number needed to treat of 4. Similarly to the COPE study, the CORE trial noted a reduction in symptoms at 72 hours in the colchicine group and showed corticosteroid use to be an independent risk factor for recurrence (57% v.25%). According to the European Cardiology guidelines for management of recurrent pericardial disease published in 2004 “colchicine was effective when NSAIDs and corticosteroids failed to prevent relapses” and “the recommended dose is 2 mg/dl for one to tow days, followed by 1mg/day (level of evidence, indication I)” (Seferovic et al., 2004).

Despite the body evidence in support of colchicine use for prevention and treatment of pericarditis, this indication remains an off label use for colchicine. Although it is relatively safe with gastrointestinal distress as the most common side effects, physicians should be aware of more serious, but infrequent, side effect of colchicine, such as bone marrow suppression, muscle damage, hepatotoxity. Of note, colchicine is renally cleared, thus in patients with renal impairment the serum level of the drug is increased and translates into a higher prevalence of adverse side effects. Thus monitoring of hepatic panel, creatinine, and complete blood count should be performed prior to therapy and 1 months after initiation.

The unpredictable nature and the disabling effects of pericarditis have generated the need for therapies geared towards preventing recurrences. In light of the data reviewed it appears that colchicine therapy is safe and effective in prevention of recurrences and management of acute symptoms and should become a more frequent part of our arsenal in the management of pericarditis.

 

Reviewed by Robert Donnino MD, NYU Division of Cardiology

References

Adler Y, Finkelstein Y, Guindo J, de la Serna A,Rodrgues, ShoenfeldY, Bayes-Genis A, Sagie A, de Luna, Bayes A, Spodick DH. Colchicine Treatment for Recurrent Pericarditis: A decade of Experience. Circulation. 1998; 97:2183-2185.

Fowler NO. Recurrent pericarditis. Cardiology Clin. 1990;8:621-626.

Imazio M, Bobbio M, Cecchi E, Demarie d, Pomari F, Morattu M, Ghisto A, Belli R, TrincheroR. Colchicine as First-Choice Therapy for Recurrent Pericarditis: Results of the CORE (COlchicine for Recurrent pericarditis) Trial. Archive of Internal Medicine. 2005;165:1987-1991.

Imazio M, Bobbio M, Cecchi E, Demarie D, Demichelis B, Pomari F, Moratti M, Gaschino G, Giammaria M, Ghisio A, Belli R, Trinchero R. Colchicine in Addition to Conventional Therapy for Acute Pericarditis: Results of the COlchicine for acute PEricarditis (COPE) Trial. Circulation. 2005;112:2012-2016.

Imazio M; Demichelis B; Parrini I; Giuggia M; Cecchi E; Gaschino G; Demarie D; Ghisio A; Trinchero R . Day-hospital treatment of acute pericarditis: a management program for outpatient therapy. Journal of American College of Cardiology. 2004 March 17;43(6):1042-6.

Imazio M, Demichelis B, Parrini I, Giuggia M, Cecchi E, Gaschino G, Demarie D, Ghisio A, Trinchero R. Day-Hospital Treatment of Acute Pericarditis: A management Program for Outpatient Therapy. Journal of the American College of Cardiology. 2004; 43:1042-1046.

Markel G, Imazio M, Brucato A, Adler Y. Colchicine for the Prevention of Recurrent Pericarditis. IMAJ. 2008;10: 69-72.

Seferovic PM, Ristic AD, Erbel R, Reinmuller R, Adler Y, Tomkowski WZ, thiene G, Yacoub M. Guidelines on the Diagnosis and Management of Pericardial Disease Executive Summary: The Task Force on the Diagnosis and Management of Pericardial Diseases of the European of Cardiology. European Heart Journal (2004) 25, 587-610.

Shabetai R. Recurrent pericarditis. In: Rose BD, ed. Up-to-Date. Wellesley, Mass:UptoDate Online; 2005.

Soler-Soler J, Sagrista-Sauleda J, Permanyer-Miralda G. Relapsing pericarditis. Heart. 2004; 90:1364-1368.

2 Responses to What is the Role of Colchicine in Recurrent Pericarditis?

  1. maslansky on April 1, 2009 at 1:56 pm

    Perhaps this is ancient history but then I’m ancient. It was presumed many years ago that colchicine was contraindicated in first trimester pregnancy. If true, and I may be mistaken, it would be worth a mention.

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