Anti-inflammatory treatment for carditis in acute rheumatic fever

Cochrane Database Syst Rev. 2012 Jun 13;(6):CD003176. doi: 10.1002/14651858.CD003176.pub2.


Background: Rheumatic heart disease remains an important cause of acquired heart disease in developing countries. Although the prevention of rheumatic fever and the management of recurrences is well established, the optimal management of active rheumatic carditis is still unclear. This is an update of a review published in 2003 and previously updated in 2009.

Objectives: To assess the effects of anti-inflammatory agents such as aspirin, corticosteroids, immunoglobulin and pentoxifylline for preventing or reducing further heart valve damage in patients with acute rheumatic fever.

Search methods: We searched the Cochrane Central Register of Controlled Trials on The Cochrane Library (Issue 3, 2011), MEDLINE (1966 to Aug 2011), EMBASE (1998 to Sept 2011), LILACS (1982 to Sept 2011), Index Medicus (1950 to April 2001) and references lists of identified studies. No language restrictions were applied.

Selection criteria: Randomised controlled trials comparing anti-inflammatory agents (e.g. aspirin, steroids, immunoglobulins, pentoxifylline) with placebo or controls, or comparing any of the anti-inflammatory agents with one another, in adults and children with acute rheumatic fever diagnosed according to the Jones, or modified Jones criteria. The presence of cardiac disease one year after treatment was the major outcome criteria selected.

Data collection and analysis: Two reviewers independently extracted data. Risk of bias was assessed using methodology outlined in the Cochrane handbook.

Main results: No new studies were included in this update. Eight randomised controlled trials involving 996 people were included. Several steroidal agents corticotrophin, cortisone, hydrocortisone, dexamethasone and prednisone, and intravenous immunoglobulin were compared to aspirin, placebo or no treatment in the various studies. Six of the trials were conducted between 1950 and 1965, one study was done in 1990, and the final study was published in 2001. Overall there was no significant difference in the risk of cardiac disease at one year between the corticosteroid-treated and aspirin-treated groups (six studies, 907 participants, relative risk 0.87, 95% confidence interval 0.66 to 1.15). Similarly, use of prednisone (two studies, 212 participants, relative risk 1.13, 95% confidence interval 0.52 to 2.45) compared to aspirin did not reduce the risk of developing heart disease after one year. Adverse events were not reported in five studies. The three studies reporting on adverse events all reported substantial adverse events. However, all results should be interpreted with caution due to the age of the studies and to substantial risk of bias.

Authors' conclusions: There is little evidence of benefit from using corticosteroids or intravenous immunoglobulins to reduce the risk of heart valve lesions in patients with acute rheumatic fever. The antiquity of most of the trials restricted adequate statistical analysis of the data and acceptable assessment of clinical outcomes by current standards. Additionally there was substantial risk of bias, so results should be viewed with caution. New randomised controlled trials in patients with acute rheumatic fever to assess the effects of corticosteroids such as oral prednisone and intravenous methylprednisolone, and other new anti-inflammatory agents are warranted. Advances in echocardiography will allow for more objective and precise assessments of cardiac outcomes.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Anti-Inflammatory Agents / therapeutic use*
  • Aspirin / therapeutic use
  • Humans
  • Immunoglobulins, Intravenous / therapeutic use
  • Myocarditis / drug therapy*
  • Randomized Controlled Trials as Topic
  • Rheumatic Heart Disease / drug therapy*
  • Steroids / therapeutic use


  • Anti-Inflammatory Agents
  • Immunoglobulins, Intravenous
  • Steroids
  • Aspirin