Aldosterone Antagonist Therapy and Mortality in Patients With ST-Segment Elevation Myocardial Infarction Without Heart Failure

Abstract

IMPORTANCE Treatment with aldosterone antagonists is recommended and has been shown to have beneficial effects in patients with ST-segment elevation myocardial infarction (STEMI) and left ventricular ejection fraction (LVEF) less than 40%. However, the role of aldosterone antagonists in patients with ejection fraction greater than 40% or without congestive heart failure is not well known. OBJECTIVES To perform a systematic review and meta-analysis using standard techniques to determine the role of therapy with aldosterone antagonists in this patient population. DATA SOURCES PubMed, Embase, CINAHL, and Cochrane Central databases were searched and a manual search for relevant references from the selected articles and published reviews was performed from database inception through June 2017. STUDY SELECTION Randomized clinical trials that evaluated treatment with aldosterone antagonists in patients with STEMI without clinical heart failure or LVEF greater than 40% were included. DATA EXTRACTION AND SYNTHESIS Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were used to conduct and report the meta-analysis, which used a random-effects model. Two investigators independently performed the database search and agreed on the final study selection. A manual search was performed for relevant references from the selected articles and published reviews. MAIN OUTCOMES AND MEASURES The outcomes analyzed were mortality, new congestive heart failure, recurrent myocardial infarction, ventricular arrhythmia, and changes in LVEF, serum potassium level, and creatinine level at follow-up. RESULTS In all, 10 randomized clinical trials with a total of 4147 unique patients were included in the meta-analysis. In patients who presented with STEMI without heart failure, treatment with aldosterone antagonists compared with control was associated with lower risk of mortality (2.4% vs 3.9%; odds ratio [OR], 0.62; 95% CI, 0.42-0.91; P = .01) and similar risks of myocardial infarction (1.6% vs 1.5%; OR, 1.03; 95% CI, 0.57-1.86; P = .91), new congestive heart failure (4.3% vs 5.4%; OR, 0.82; 95% CI, 0.56-1.20; P = .31), and ventricular arrhythmia (4.1% vs 5.1%; OR, 0.76; 95% CI, 0.45-1.31; P = .33). Similarly, treatment with aldosterone antagonists compared with control was associated with a small yet significant increase in LVEF (mean difference, 1.58%; 95% CI, 0.18%-2.97%; P = .03), a small increase in serum potassium level (mean difference, 0.07 mEq/L; 95% CI, 0.01-0.13 mEq/L; P = .02), and no change in serum creatinine level (standardized mean difference, 1.4; 95% CI, −0.43 to 3.24; P = .13). CONCLUSIONS AND RELEVANCE Treatment with aldosterone antagonists is associated with a mortality benefit in patients with STEMI with LVEF greater than 40% or without heart failure.

Mineralocorticoid receptor antagonist pre-treatment and early post-treatment to minimize reperfusion injury after ST-elevation myocardial infarction: The MINIMIZE STEMI trial

“… 20 Two large meta-analyses recently showed that the mortality benefit was mainly in those patients with post-MI heart failure 21 as well as in STEMI patients without heart failure. 22 The beneficial effects of MRA therapy on mortality could be partly due to less adverse LV remodeling, a pre-cursor of heart failure and our study provides further support for the use of MRA therapy in STEMI patients. The mechanisms whereby MRA therapy contribute to less adverse LV remodeling is likely due to blockade of aldosterone-mediated increase in collagen synthesis 23 and a reduction in extracellular matrix turnover.…”

“…The results from the pooled studies 20 and meta-analyses 21. , 22. and our study support the need for an adequately powered study and the CLEAR-SYNERGY ( NCT03048825 ) study (4000 patients; primary endpoint: composite of cardiovascular death or new or worsening heart failure at 2 years) has been designed to address this and is currently recruiting patients.…”

Macrophage Mineralocorticoid Receptor Is a Pleiotropic Modulator of Myocardial Infarct Healing

“…5 Moreover, a recent meta-analysis of data from 10 randomized placebo-controlled trials (including patients with ST-segment–elevation myocardial infarction without evidence of heart failure or severe LV dysfunction) showed that the use of MR antagonists was associated with a 38% reduction in mortality and a significant increase in LV ejection fraction during follow-up. 36,37…”

Steroid hormone secretion after stimulation of mineralocorticoid and NMDA receptors and cardiovascular risk in patients with depression

“…As well as contributing to the pathogenesis of MDD, alterations in HPA activity and glutamate signaling may also contribute to the elevated risk of CVD in depressed patients 7,25,26 . Other steroid hormones, such as increased aldosterone 27,28 and decreased DHEA-S levels 29 , are also closely linked to CVD. Importantly, increased aldosterone levels [30][31][32] and decreased DHEA-S concentrations 33 have been found in depressed patients, and both hormones interact with the glutamate system [34][35][36] .…”