Combination immune suppression with prednisolone and azathioprine (IPA) is used to treat heart failure due to chronic non-fulmintant non-viral myocarditis. However, there has been inconsistency in the effects of immunosuppression treatment.
A systematic review and meta-analysis of trials using (IPA) to treat HF refractory to OMT caused by chronic non-fulminant virus negative or "autoimmune" myocarditis was conducted to demonstrate the effect on LV EF and the combined clinical endpoint of cardiovascular mortality and/or HTx-free survival.
Methods and results
All trials with using IPA versus OMT were searched using OVID Medline and ClinicalTrials.gov, following the PRISMA guidelines. Missing clinical outcome data was 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 4 trials were identified. Two were published RCT, one was an aborted RCT without publication but randomised and treated 20 patients and one was a published registry with a corresponding control group, resulting in a total of 369 patients.
IPA on top of OMT did not improve LVEF (mean difference 9.9% [95% confidence interval -1.8, 21.7]). Because of the significant heterogeneity (I296.8%, p<0.001) we performed a subanalysis of this result. First, the studies were divided by whether RCT or not, where I2values remained similar (96.9%). Then, they were sub-grouped by whether published or not, which did not reduce I2-values but the pooled estimates of the change in LVEF became significantly positive with 14% [1.4, 26.6].
A trend towards a benefit in the combined endpoint of cardiovascular mortality and/or heart transplantation-free survival was observed with the intervention but did not reach clinical significance (risk ratio 0.34 [0.08, 1.51]). Because of a moderate heterogeneity (I2= 60%), we again performed a subgroup analyses. When categorised by RCT or not, heterogeneity significantly dropped close to low level (32%) with no difference in the pooled RR of the RCTs. Sub-grouping by publication status increased heterogeneity to almost high category (I2=72.9%).
At the moment, there is insufficient evidence supporting functional and prognostic benefits of IPA added to OMT in virus negative inflammatory positive cardiomyopathy.
There is a potential positive effect on both LV EF and the combined endpoint of cardiovascular mortality or HTx-free survival. Significant heterogeneity exist among individual publications regarding diagnosis, dose regime, duration of therapy, study design and quality of the data. More research is needed to elucidate the exact impact of this treatment. Further adequate-powered well-designed prospective RCTs should be warranted to explore the potential effects of adding immunosuppressive therapy to OMT.