Prednisone and azathioprine in patients with inflammatory cardiomyopathy: systematic review and meta-analysis

Aims Chronic non-viral myocarditis, also called inflammatory cardiomyopathy, can be treated with immune suppression on tops of optimal medical therapy (OMT) for heart failure, using a combination of prednisolone and azathioprine (IPA). However, there has been inconsistency in the effects of immunosuppression treatment. This meta-analysis is the first to evaluate all available data of the effect of this treatment on left ventricular ejection fraction (LVEF) and the combined clinical endpoint of cardiovascular mortality and/or heart transplantation-free survival.

Methods and results All trials with using IPA vs. OMT in this syndrome were searched using OVID Medline and ClinicalTrials.gov, following the PRISMA guidelines. Missing data were retrieved after contacting the corresponding authors. All data was reviewed and analysed using and standard meta-analysis methods. A random effect model was used to pool the effect sizes. A total of four trials (three randomised controlled trials and one propensity-matched retrospective registry) including 369 patients were identified. IPA on top of OMT did not improve LVEF [mean difference 9.9% (95% confidence interval -1.8, 21.7)] with significant heterogeneity. When we limited our pooled estimate to the published studies only, significant LVEF improvement by IPA was observed [14% (1.4, 26.6)]. No cardiovascular mortality benefit was observed with the intervention [risk ratio 0.34 (0.08, 1.51)].

Conclusions At the moment, there is insufficient evidence supporting functional and prognostic benefits of IPA added to OMT in virus negative inflammatory positive cardiomyopathy. Further adequate-powered well-designed prospective RCTs should be warranted to explore the potential effects of adding immunosuppressive therapy to OMT.