Acute myocardial infarction
Based on the results from the EPHESUS study, the REMINDER trial (Impact Of Eplerenone On Cardiovascular Outcomes In Patients Post Myocardial Infarction) demonstrated that eplerenone administration during the acute phase of STEMI in patients without HF was safe and well tolerated, and associated with improvement in the primary outcome (mainly driven by a reduction in BNP/NT-proBNP levels at follow-up). There was a trend towards a greater benefit when eplerenone was administrated at 6 hours (Montalescot et al., 2014). Interestingly, eplerenone reduced collagen type III peptide levels. This may limit extracellular matrix formation in post-MI patients without HF, contributing to the clinical benefits of this therapy (Ferreira et al., 2018). However, the ALBATROSS randomized clinical trial (Aldosterone Lethal Effects Blockade in Acute Myocardial Infarction Treated With or Without Reperfusion to Improve Outcome and Survival at Six Months Follow-up) failed to show a benefit of canrenoate/spironolactone treatment initiated early in patients with acute MI (including STEMI and NSTEMI) without HF. Nevertheless it reported a reduction of mortality only in the ST-segment elevation MI subgroup (Beygui et al., 2016). It is important to highlight that both REMINDER and ALBATROSS were underpowered to detect treatment effect differences in morbidity and mortality. However, in a pre-specified meta-analysis of patient-level data of the STEMI patients from both studies, MRA treatment in acute STEMI was associated with a reduction of death, and death or resuscitated sudden death (Beygui et al., 2018).
The MINIMIZE STEMI trial (MR antagonist pre-treatment and early post-treatment to minimize reperfusion injury after ST-elevation myocardial infarction) did not show a benefit of canrenoate or spironolactone therapy in reducing MI size when applied prior to reperfusion, but there was an improvement on LV remodeling at 3 months in STEMI patients without HF (Bulluck et al., 2019).