Aldosterone antagonists for STEMI without heart failure
Details:
-- 10 international RCTs were included, with a total of 4147 unique patients who had STEMI without heart failure.
-- The studies are in general quite short, only 2 had follow-up for one year. Others were 6 months or less
-- all patients had initial treatment with a percutaneous coronary intervention (PCI) or thrombolysis
-- Main outcomes: mortality, MI, new CHF, ventricular arrhythmias, change in left ventricular ejection fraction (LVEF), serum creatinine level, and potassium levels
Results:
-- comparing the use of aldosterone antagonist vs control:
-- 38% decreased mortality, 2.4% vs 3.9%, OR 0.62 (0.42-0.91), p=0.01
-- no significant benefit for risks of recurrent MI, new congestive heart failure, or ventricular arrhythmias
-- small but significant increase in LVEF: mean difference, 1.58% (0.18%-2.97%), p=0.03
-- small increases serum potassium levels: mean difference 0.07 mEq/L (0.01-0.13 mEq/L), p=0.02
-- no changes serum creatinine level
Commentary:
-- based on documented evidence (eg EPHESUS study of patients having an acute MI complicated by heart failure and LVEF <40% and treated with eplerenone, finding a 15% decreased mortality), aldosterone antagonists are now recommended in patients with ST-segment elevation MI and LVEF <40%. The current review found benefit in those with LVEF >40%. Of note, both the EPHESUS study and the current meta-analysis did NOT find any decrease in subsequent MIs (though EPHESUS did find a decrease in subsequent heart failure)
-- despite clear benefit from revascularization with PCI or thrombolysis, STEMI is still associated with significant morbidity/mortality, up to 23% within 5 years.
-- Aldosterone has been linked to the development of ventricular remodeling/tissue fibrosis, and high levels are associated with worse clinical outcomes, including increased mortality. Aldosterone antagonists may counteract this, and there are also suggestions that they may decrease the aldosterone-associated macrophage accumulation and activation, inflammatory cytokines, reactive oxygen species/oxidative stress, and vascular effects (aldosterone can lead to either vasodilation/higher nitric oxide effects or lower NO synthesis/endothelial dysfunction/vasoconstriction, the latter especially if chronically elevated: see https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3579277/ ) .
-- This meta-analysis brings together several studies on aldosterone antagonists which by themselves did not necessarily show benefit, though in the aggregate did find the pretty dramatic (38%) decreased mortality.
-- the limitation of this type of meta-analysis is the large disparity of the different studies, in terms of aldosterone antagonist use, mode of administration, concomitant therapies, duration of follow-up. Also the number of patients in the different studies was quite different, allowing the largest trial (ALBATROSS study) to render disproportionate weight to the results
-- unfortunately this meta-analysis did not show the results of longer vs shorter follow-up, though did comment that those with 6 to 12 months did have a reduced mortality risk associated with therapy. A longer RCT seems appropriate to appreciate the overall effects of aldosterone antagonists.
so, i must admit that i am pretty impressed with aldosterone antagonists (spironolactone being the one used most). high levels of aldosterone do seem to lead to unfortunate physiologic consequences, as above. Spironolactone is perhaps the best add-on med in those with refractory hypertension (see http://gmodestmedblogs.blogspot.com/2015/09/spironolactone-in-drug-resistant.html ) and heart failure with preserved ejection fraction (see http://gmodestmedblogs.blogspot.com/2017/06/spironolactone-helps-heart-failure-with.html ). this study adds to the mix, showing mortality benefit when used right after a STEMI without heart failure.
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