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Clinical Study
Received: November 18, 2003Accepted after revision: March 16, 2004 The Efficacy of Colchicine in the Treatment of
Recurrent Pericarditis Related to Postcardiac
Injury (Postpericardiotomy and Postinfarcted)
Syndrome: A Multicenter Analysis
Alexander Tenenbaum a Nira Koren-Moragb David H. Spodickc Antonio Brucatod Antoni Bayes-de-Lunae Giovanni Brambillad Enrique Z. Fismana Galit Artoma Joseph Guindoe Antoni Bayes-Genise aCardiac Rehabilitation Institute, Sheba Medical Center, Tel-Hashomer, bSackler School of Medicine,Tel Aviv University, Tel Aviv, Israel; cUniversity of Massachusetts Medical School, Department of Medicine,Division of Cardiovascular Medicine, Worcester, Mass., USA; dDepartment of Medicine Brera,Rheumatology, Niguarda Ca’Granda Hospital, Milan, Italy; eService of Cardiology,Hospital de la Santa Creu i Sant Pau, Barcelona, Spain For editorial comment see p. 140
Key Words
There were 28 patients, 18 male (64%) and 10 female Pericarditis W Colchicine W Postcardiac injury syndrome W (36%), ranging in age from 21 to 82 years (mean 53 B 15 Postpericardiotomy syndrome W Postmyocardial years). PCIS pericarditis was secondary to pericardioto- my in 19 patients and infarction in 9. In 21 patients (75%),colchicine therapy was discontinued during follow-upand renewed only in the case of relapse. In these Abstract
patients, the total period of treatment was summed up Background: Pericarditis related to the postcardiac injury
for analysis. 7 patients (25%) were taking colchicine as a syndrome (PCIS) following myocardial infarction or car- permanent treatment, and no colchicine-free follow-up diac surgery is a troublesome and often recurrent clinical was documented. In total, 130 recurrences (mean 4.64 B entity resistant to therapeutic interventions. The useful- 3.7 per patient, range 2–16) were noted before colchicine ness of colchicine in the prevention of recurrent PCIS has therapy was initiated. During colchicine treatment (mean not been evaluated. Objective: We performed a cumula-
duration of treatment 16.6 B 13.5 months), a significant tive analysis of available multicenter data with the aim of reduction in the number of recurrences was observed.
evaluating the efficacy of colchicine in the treatment of Only 5 of 28 patients (18%) presented with new recur- recurrent PCIS. Methods and Results: The study was
rences (mean 0.25 B 0.59 vs. 4.64 B 3.7 per patient in the designed as a multicenter all-cases analysis. Re- precolchicine period, p ! 0.001). The mean follow-up searchers who had published studies and case reports period after colchicine discontinuation (data were avail- on colchicine treatment in recurrent pericarditis related able for 21 patients) was 31.9 B 28 months; during fol- to PCIS during the last 15 years were approached and low-up, 13 patients (62%) remained recurrence free and asked to contribute all available cases to the database.
8 of them (38%) experienced relapses (mean 0.43 B 0.6 Tel. +972 58 547138, Fax +972 3 5303079, E-Mail adlery@sheba.health.gov.il per patient, p ! 0.001 vs. precolchicine). Conclusions: It
A total of 140 cases were screened initially to investigate the fol- seems that colchicine may be effective in preventing new (1) PCIS etiology of pericarditis (postpericardiotomy or postin- relapses in patients with recurrent pericarditis related to postcardiac injury both during active therapy and after (2) clinical diagnosis of two or more relapses of acute pericarditis before institution of colchicine therapy; (3) therapeutic trial of colchicine beyond its use during the taper- (4) complete documented follow-up since the first episode of Introduction
acute pericarditis including reports on therapeutic trials with cortico-steroids, and continuing for at least 1 month following initiation of Late pericarditis following myocardial infarction (5) colchicine dose of 1 mg/day for a prolonged period to achieve (Dressler’s syndrome) or cardiac surgery (Dressler’s-like syndrome) is referred to as postmyocardial infarction syn- In particular, data were considered complete only in patients with drome (PMIS) or postpericardiotomy syndrome, respec- a methodical follow-up since the first episode of acute pericarditis, tively [1, 2]. The term postcardiac injury syndrome including precise information about the following predefined clini- (PCIS) is used to encompass both these entities [3, 4].
cally relevant variables: age, sex, etiology of pericarditis, duration offollow-up since the first episode of pericarditis, use of corticosteroid PCIS is characterized by fever, pleuropericardial pain, therapy, number of relapses before initiation of colchicine treatment, pericarditis and pulmonary involvement. Evidence sup- duration of colchicine treatment and duration of follow-up after dis- ports an immunopathic etiology of this syndrome. Cur- continuation of colchicine treatment. In addition, precise informa- rently, the classical postmyocardial infarction Dressler’s tion needed to be documented about the number of relapses during syndrome has been rendered a rare phenomenon among colchicine treatment as well as during follow-up after discontinuationof colchicine treatment (postcolchicine). Twenty-one patients had to patients who benefit from early revascularization [5]. In be excluded due to the lack of definitive age data or a colchicine dose contrast, the incidence of postpericardiotomy syndrome different from 1 mg/day. In 91 patients, the etiology of pericarditis is high and varies from 13% [6] to 47% [7].
was other than PCIS (mainly idiopathic); these patients were also Postpericardiotomy syndrome is a troublesome and excluded. Therefore, the final study sample comprised 28 patients often recurrent clinical entity [6–10]. Accepted modalities with PCIS pericarditis who met the inclusion criteria.
Results are expressed as mean values B SD for continuous vari- of PMIS treatment have traditionally included nonsteroi- ables and as frequency and percentage for categorical variables.
dal anti-inflammatory drugs (NSAIDs), corticosteroids, Comparison of categorical characteristics was performed by ¯2 analy- immunosuppressive agents and, in unremitting cases, sis and Fisher’s exact test. A t test was performed for continuous vari- pericardiectomy (usually unsuccessful), while relapses ables. A p value ! 0.05 was considered significant. Correlations may occur during attempts to reduce drug dose. Unfortu- between all continuous variables were conducted by Pearson correla-tion.
nately, recurrent pericarditis may be a debilitating diseaseresistant to therapeutic interventions [6–11].
Recently, the first study to demonstrate the benefits of colchicine for the primary prevention of postpericardioto-my syndrome in patients after cardiac surgery was pub- In this study, there were 28 patients, 18 male (64%) lished [12]. However, the usefulness of colchicine in the and 10 female (36%), ranging in age from 21 to 82 years prevention of recurrent PMIS has not been evaluated.
Therefore, we decided to perform a cumulative analy- B 15 years). PCIS pericarditis was secondary to pericardiotomy in 19 patients and infarction in 9. In 21 sis of all available multicenter data in order to evaluate patients (75%), colchicine therapy was discontinued dur- the efficacy of colchicine in treatment of recurrent PCIS.
ing follow-up and renewed only in the case of relapse. Inthese patients, the total length of treatment was summedup for analysis. Seven patients (25%) were taking colchi- cine as a permanent treatment, and no colchicine-free fol- The study was designed as a multicenter all-cases analysis.
Researchers who had published studies and case reports on colchi- Despite treatment with NSAIDs, corticosteroids, peri- cine treatment in recurrent pericarditis of any etiology during the last cardiocentesis or some combination thereof, all patients 15 years were approached and asked to contribute all available cases (100%) experienced relapses before inclusion in this to the database. Patient data were obtained from Italy (n = 44), Spain(n = 33), France (n = 37), Israel (n = 20), Lebanon (n = 3), Turkey (n = study, representing statistics arising from the definition.
In total, 130 recurrences (mean 4.64 B 3.7 per patient, Table 1. Follow-up duration and number
of relapses in study patients
Figures in parentheses represent percentages.
Table 2. Pearson correlation coefficients between duration of follow-up, number of relapses and age of patients with
PCIS
‘Before’, ‘during’ and ‘after’ refer to the periods before, during and after colchicine treatment. * p ! 0.05.
range 2–16) were noted before colchicine therapy was ini- before colchicine treatment (r = 0.49, p = 0.008). No cor- tiated. During colchicine treatment (mean duration of relation was found between the duration of colchicine treatment 16.6 B 13.5 months), a significant reduction in treatment and number of relapses before colchicine treat- the number of recurrences was observed (table 1). Only 5 ment. There was no correlation between the numbers of of 28 patients (18%) presented with new recurrences relapses in each period of follow-up; in particular, there (mean 0.25 B 0.59 vs. 4.64 B 3.7 per patient in the pre- was no connection between the number of relapses before colchicine period, p ! 0.001). The mean length of follow- colchicine treatment and the number of relapses under up after colchicine discontinuation (data were available colchicine treatment or after its discontinuation.
for 21 patients) was 31.9 B 28 months; during follow-up,13 of these patients (62%) remained recurrence free and 8of them (38%) experienced relapses (mean 0.43 B 0.6 per Discussion
patient, p ! 0.001 vs. precolchicine). The recurrencesafter colchicine discontinuation were generally minor and Colchicine has traditionally been used for the treat- were effectively controlled in all patients by the reinstitu- ment of gout. The complex actions of this substance, tion of colchicine therapy. Gastrointestinal side effects which are mainly attributable to its stabilizing action on were minor (diarrhea and nausea) and resolved in all the cytoskeleton and cell membranes, and its special pat- tern of distribution form the basis for the results present- Table 2 details the correlations between age, number of ed here regarding the prophylactic or therapeutic actions relapses in each period and the duration of follow-up and of colchicine in a whole range of other diseases. This is all treatment. As expected, there was a significant correlation the more significant in that in several instances it con- between the duration of follow-up and number of relapses cerns diseases that have so far been unsatisfactorily con- Pericarditis Related to Postcardiac InjurySyndrome trolled by other treatments [13]. The present multicenter randomized placebo-controlled double-blind trial may analysis demonstrates that colchicine is effective in pre- provide a definitive conclusion regarding optimal therapy venting recurrences of pericarditis in PCIS. These results for recurrent PCIS. However, in the absence of these data, are especially important, since the study included patients the analysis of the present database provides an important with a high risk of recurrence (on average, more than 4 source of information to guide the treatment of this prob- Considering the natural course of the disease, which is characterized by periodical relapses [14], it might havebeen expected that patients would experience new recur- Conclusions
rences after discontinuation of therapy. However, duringa mean follow-up period of more than 2 years, 62% of the It seems that colchicine may be effective in preventing patients in whom colchicine was discontinued remained new relapses in patients with recurrent pericarditis related free from new relapses. The absence of a correlation to postcardiac injury both during active therapy and after between the numbers of relapses per patient in the differ- ent periods of follow-up (before, during and after colchi-cine) indeed supports the concept that colchicine therapyprovides sustained benefit even after discontinuation of Acknowledgments
We want to thank our fellow researchers for contributing impor- tant cases: Dr. Ercan Tutar from the Department of Pediatric Car-diology, Ankara University Medical School, Turkey; Dr. Giuseppe Study Limitations
Sforza from the Dipartemento di Cardiologia, Ospedale ‘ImmacolataConcezione’, Padova, Italy; Dr. Søren Madsen from the Department The present study is an analysis of patients with recur- of Medical Gastroenterology, Copenhagen University Hospital inGentofte, Hellerup, Denmark, and Dr. Granel Brigitte, Service de rent PCIS with substantial variation in the number of pre- Medicine Interne, Hopital de la Timone, Marseille, France.
vious relapses and the timing of instituting colchicinetherapy as well as treatment duration. Eventually, only a References
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