International collaborative systematic review of controlled clinical trials on pharmacologic treatments for acute pericarditis and its recurrences

doi:10.1016/j.ahj.2010.06.015

American Heart Journal

Volume 160, Issue 4, October 2010, Pages 662-670

https://doi.org/10.1016/j.ahj.2010.06.015 Get rights and content

Background

Acute pericarditis is common, yet uncertainty persists on its treatment. We thus aimed to conduct a comprehensive systematic review on pharmacologic treatments for acute or recurrent pericarditis.

Methods

Controlled clinical studies were searched in several databases and were included provided they focused on pharmacologic agents for acute pericarditis or its recurrences. Random-effect odds ratios (ORs) were computed for long-term treatment failure, pericarditis recurrence, rehospitalization, and adverse drug effects.

Results

From 2,078 citations, 7 studies were finally included (451 patients); but only 3 were randomized trials. Treatment comparisons were as follows: colchicine versus standard therapy (3 studies, 265 patients), steroids versus standard therapy (2 studies, 31 patients), low-dose versus high-dose steroids (1 study, 100 patients), and statins versus standard therapy (1 study, 55 patients). Colchicine was associated with a reduced risk of treatment failure (OR = 0.23 [0.11-0.49]) and recurrent pericarditis (OR = 0.39 [0.20-0.77]), but with a trend toward more adverse effects (OR = 5.27 [0.86-32.16]). Overall, steroids were associated with a trend toward increased risk of recurrent pericarditis (OR = 7.50 [0.62-90.65]). Conversely, low-dose steroids proved superior to high-dose steroids for treatment failure or recurrent pericarditis (OR = 0.29 [0.13-0.66]), rehospitalizations (OR = 0.19 [0.06-0.63]), and adverse effects (OR = 0.07 [0.01-0.54]). Data on statins were inconclusive.

Conclusions

Clinical evidence informing decision-making for the management of acute pericarditis and its recurrences is still limited to few, small, and/or low-quality clinical studies. Notwithstanding such major caveats, available studies routinely using nonsteroidal anti-inflammatory agents in both experimental and control groups suggest a beneficial risk-benefit profile for colchicine and a detrimental one for steroids, especially when used at high dosages.

Section snippets

Methods

The present review was carried out in keeping with The Cochrane Collaboration, QUOROM, and MOOSE.8, 9, 10 Extramural funding in support of this work was provided by the Agenzia Italiana del Farmaco, with grant FARM7X58KC. No individual beyond the listed authors and no other organization contributed in any substantive way to the writing or editing of the paper or performance of any analyses described therein. Thus, the authors are solely responsible for the design and conduct of this study, all

Results

From an initial sample of 2,078 citations, 2,026 were excluded at the title/abstract level because of being nonpertinent or evident duplicates. Thus, 52 citations were appraised in complete form, leading to the final inclusion of 7 controlled clinical studies (Table I)14, 15, 16, 17, 18, 19, 20 and the exclusion of a further 45 citations for the following reasons: duplicate reports (n = 4), case reports or series (n = 7), noncontrolled studies (n = 17), reviews or editorials (n = 7), and

Discussion

This systematic review has the following implications: (a) only few, small, and/or low-quality clinical studies are available on the pharmacologic management of acute pericarditis and its recurrences; (b) all such studies used routinely nonsteroidal anti-inflammatory agents as background therapy in both experimental and control groups; (c) meta-analytic pooling of available data suggests a beneficial risk-benefit profile for colchicine and a detrimental risk-benefit profile for steroids,

Disclosures

Conflicts of interest: none pertinent to this work.

This work was supported by the Agenzia Italiana del Farmaco (AIFA), with grant FARM7X58KC.

Acknowledgements

This work is part of a senior investigator project for METCARDIO Group, Turin, Italy (Protocol #5-2008 at http://www.metcardio.org/protocols.html).

References (25)

TroughtonR.W. et al.
Pericarditis
Lancet
(2004)
RaatikkaM. et al.
Recurrent pericarditis in children and adolescents. Report of 15 cases
J Am Coll Cardiol
(2003)
ImazioM. et al.
Management, risk factors, and outcomes in recurrent pericarditis
Am J Cardiol
(2005)
BoccardiL. et al.
Chest pain in women: a multicenter study of the National Association of Hospital Cardiologists (ANMCO) of the Lazio Region
Ital Heart J Suppl
(2002)
LittleW.C. et al.
Pericardial disease
Circulation
(2006)
LangeR.A. et al.
Acute pericarditis
N Engl J Med
(2004)
Soler-SolerJ. et al.
Relapsing pericarditis
Heart
(2004)
ImazioM. et al.
Pathogenesis, management, and prevention of recurrent pericarditis
J Cardiovasc Med (Hagerstown)
(2007)
MaischB. et al.
Guidelines on the diagnosis and management of pericardial diseases. Executive summary
Eur Heart J
(2004)
Biondi-ZoccaiG.G. et al.
Compliance with QUOROM and quality of reporting of overlapping meta-analyses on the role of acetylcysteine in the prevention of contrast associated nephropathy: case study
BMJ
(2006)

StroupD.F. et al.

Meta-analysis of observational studies in epidemiology: a proposal for reporting

JAMA

(2000)

Higgins JPT, Green S (editors). Cochrane handbook for systematic reviews of interventions version 5.0.1 [updated...

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Clinical InvestigationAcute Ischemic Heart DiseaseInternational collaborative systematic review of controlled clinical trials on pharmacologic treatments for acute pericarditis and its recurrences

Background

Methods

Results

Conclusions

Section snippets

Methods

Results

Discussion

Disclosures

Acknowledgements

Lancet

J Am Coll Cardiol

Am J Cardiol

Chest pain in women: a multicenter study of the National Association of Hospital Cardiologists (ANMCO) of the Lazio Region

Ital Heart J Suppl

Pericardial disease

Circulation

Acute pericarditis

N Engl J Med

Relapsing pericarditis

Heart

Pathogenesis, management, and prevention of recurrent pericarditis

J Cardiovasc Med (Hagerstown)

Guidelines on the diagnosis and management of pericardial diseases. Executive summary

Eur Heart J

Compliance with QUOROM and quality of reporting of overlapping meta-analyses on the role of acetylcysteine in the prevention of contrast associated nephropathy: case study

BMJ

Meta-analysis of observational studies in epidemiology: a proposal for reporting

JAMA

Clinical Investigation
Acute Ischemic Heart Disease
International collaborative systematic review of controlled clinical trials on pharmacologic treatments for acute pericarditis and its recurrences