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Journal ArticleDOI

Eplerenone, a Selective Aldosterone Blocker, in Patients with Left Ventricular Dysfunction after Myocardial Infarction

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TLDR
The addition of eplerenone to optimal medical therapy reduces morbidity and mortality among patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure.
Abstract
background Aldosterone blockade reduces mortality and morbidity among patients with severe heart failure. We conducted a double-blind, placebo-controlled study evaluating the effect of eplerenone, a selective aldosterone blocker, on morbidity and mortality among patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure. methods Patients were randomly assigned to eplerenone (25 mg per day initially, titrated to a maximum of 50 mg per day; 3313 patients) or placebo (3319 patients) in addition to optimal medical therapy. The study continued until 1012 deaths occurred. The primary end points were death from any cause and death from cardiovascular causes or hospitalization for heart failure, acute myocardial infarction, stroke, or ventricular arrhythmia. results During a mean follow-up of 16 months, there were 478 deaths in the eplerenone group and 554 deaths in the placebo group (relative risk, 0.85; 95 percent confidence interval, 0.75 to 0.96; P=0.008). Of these deaths, 407 in the eplerenone group and 483 in the placebo group were attributed to cardiovascular causes (relative risk, 0.83; 95 percent confidence interval, 0.72 to 0.94; P = 0.005). The rate of the other primary end point, death from cardiovascular causes or hospitalization for cardiovascular events, was reduced by eplerenone (relative risk, 0.87; 95 percent confidence interval, 0.79 to 0.95; P=0.002), as was the secondary end point of death from any cause or any hospitalization (relative risk, 0.92; 95 percent confidence interval, 0.86 to 0.98; P=0.02). There was also a reduction in the rate of sudden death from cardiac causes (relative risk, 0.79; 95 percent confidence interval, 0.64 to 0.97; P=0.03). The rate of serious hyperkalemia was 5.5 percent in the eplerenone group and 3.9 percent in the placebo group (P = 0.002), whereas the rate of hypokalemia was 8.4 percent in the eplerenone group and 13.1 percent in the placebo group (P<0.001). conclusions The addition of eplerenone to optimal medical therapy reduces morbidity and mortality among patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure.

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Citations
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Journal ArticleDOI

Glucocorticoid-Related Signaling Effects in Vascular Smooth Muscle Cells

TL;DR: It is concluded that corticosterone induces rapid mineralocorticoid receptor signaling in vascular smooth muscle cells that involves mitogen-activated protein kinase kinase/extracellular signal–regulated kinase–dependent pathways, which suggest that glucocortioids may contribute to vascular disease via mineralocortsin receptor signaling, independent of circulating aldosterone.
Journal ArticleDOI

Overcoming undesirable CYP1A2 inhibition of pyridylnaphthalene-type aldosterone synthase inhibitors: influence of heteroaryl derivatization on potency and selectivity.

TL;DR: The influence of substituents in the heterocycle of lead structures with a naphthalene molecular scaffold is examined to overcome a strong inhibition of the hepatic drug-metabolizing enzyme CYP1A2.
Journal ArticleDOI

Risk factors for hyperkalaemia in a cohort of patients with newly diagnosed heart failure: a nested case–control study in UK general practice

TL;DR: The aim of this study was to identify risk factors for hyperkalaemia in a cohort of patients with newly diagnosed heart failure in the UK.
Journal ArticleDOI

True rate of mineralocorticoid receptor antagonists-related hyperkalemia in placebo-controlled trials: A meta-analysis.

TL;DR: This meta‐analysis shows that in clinical trials, 54% of hyperkalemia cases were specifically related to the MRA treatment and 46% to other reasons, and non–MRA‐related rises in potassium levels might be underestimated and should be rigorously explored before cessation of the evidence‐based therapy with MRAs.
Journal ArticleDOI

Spironolactone use at discharge was associated with improved survival in hospitalized patients with systolic heart failure

TL;DR: Among patients with HF hospitalized for systolic dysfunction, spironolactone use at the time of discharge was associated with long-term survival benefit, providing further support for the idea that spironOLactone may be useful in patients hospitalized with HF and reduced LVEF.
References
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Journal ArticleDOI

Prediction of Creatinine Clearance from Serum Creatinine

Donald W. Cockcroft, +1 more
- 01 Jan 1976 - 
TL;DR: A formula has been developed to predict Creatinine clearance from serum creatinine (Scr) in adult males: Ccr = (140 – age) (wt kg)/72 × Scr (mg/100ml) (15% less i).
Journal ArticleDOI

The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators.

TL;DR: Blockade of aldosterone receptors by spironolactone, in addition to standard therapy, substantially reduces the risk of both morbidity and death among patients with severe heart failure.
Journal ArticleDOI

Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomised trial.

TL;DR: In patients treated long-term after an acute myocardial infarction complicated by left-ventricular systolic dysfunction, carvedilol reduced the frequency of all-cause and cardiovascular mortality, and recurrent, non-fatal myocardia infarctions.
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