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).