Serum microRNAs and antifibrotic response to eplerenone in acute myocardial infarction complicated by systolic dysfunction

Background: After myocardial infarction (MI) complicated by heart failure (HF), eplerenone reduced serum con-centrations of amino-terminal propeptide of type III collagen (PIIINP) and carboxy-terminal propeptide of type I collagen (PICP). Determining a subgroup who are more prone to decrease their collagen content and to respond better to the antifibrotic effects of mineralocorticoid receptor antagonists (MRA) may be relevant for a personal-ized treatment approach. Whether circulating microRNAs may identify a subgroup that have experienced a more pronounced antifibrotic effect of eplerenone as measured by a PICP and PIIINP decrease is unclear. Methods: A set of circulating microRNAs linked to cardiac fibrosis (mir-1, mir-21, mir-29a, mir-29b, mir-101, mir -122, mir-133a) were measured at baseline in 198 patients in the biomarker substudy of Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS). Associations between baseline microRNA levels and changes in both PIIINP and PICP from baseline to month 9 were studied using multivariable analysis of covariance, adjusting for age, sex, history of hypertension and diabetes mellitus, prescription of ACE-inhibitors or angiotensin receptor blockers, baseline PIIINP or PICP, and eplerenone treatment. Furthermore, a treatment-by-microRNA interaction was studied. Results: From the selected microRNAs, only mir-133a was associated with a PICP decrease (ss-6.43, 95%CI-12.71 to -0.15,p = 0.045). None of the microRNAs was associated with a PIIINP change. The microRNAs did not predict an effect of eplerenone on PICP and PIIINP changes. Conclusion: Although serum mir-133a was associated with PICP change, none of the microRNAs previously linked to cardiac fibrosis predicted an antifibrotic response to eplerenone. Further study is needed to identify other suit-able targets for a personalized treatment approach. (c) 2021 Elsevier B.V. All rights reserved.

Automated summary

The study found that only mir-133a was associated with a decrease in PICP after eplerenone treatment, while none of the microRNAs predicted changes in PIIINP. However, these microRNAs did not predict the effect of eplerenone on PICP and PIIINP changes. Further research is needed to identify suitable targets for personalized treatment approaches.