Journal ArticleDOI
Eplerenone, a Selective Aldosterone Blocker, in Patients with Left Ventricular Dysfunction after Myocardial Infarction
Bertram Pitt,Willem J. Remme,Faiez Zannad,James D. Neaton,Felipe Martinez,Barbara Roniker,Richard Bittman,Steve Hurley,Jay H. Kleiman,Marjorie Gatlin +9 more
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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.read more
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Steroidogenesis vs. steroid uptake in the heart: do corticosteroids mediate effects via cardiac mineralocorticoid receptors?
Wenxia Chai,Johannes Hofland,Pieter M. Jansen,Ingrid M. Garrelds,René de Vries,Antoon J. van den Bogaerdt,Richard A Feelders,Frank H. de Jong,A.H. Jan Danser +8 more
TL;DR: Measurements of steroid-synthesizing enzyme gene expression levels in human ventricular and atrial tissue pieces from heart-beating organ donors, patients with end-stage heart failure and hypertrophic cardiomyopathy patients revealed that under no condition, the human heart was capable of synthesizing aldosterone or cortisol de novo.
Journal ArticleDOI
Long-term safety, tolerability and efficacy of aliskiren in combination with valsartan in patients with hypertension: a 6-month interim analysis.
Steven G. Chrysant,Alexander V. Murray,Uta C. Hoppe,Dan Dattani,Samir Patel,Huang Hsu,Jack Zhang +6 more
TL;DR: The findings show that long-term treatment with the aliskiren/valsartan 300/320-mg combination provided clinically significant BP lowering, was well-tolerated and was associated with a very low rate of potassium elevations in patients with hypertension.
Journal ArticleDOI
Aldosterone enhances ligand-stimulated nitric oxide production in endothelial cells.
TL;DR: Aldosterone acutely enhances ligand-mediated endothelial NO production by eplerenone-sensitive mechanisms involving a PI3K that may synergize Ca2+-dependent eNOS phosphorylation at Ser1179.
Journal ArticleDOI
Mode of death in patients with newly diagnosed heart failure in the general population.
Paresh A Mehta,Simon W Dubrey,Hugh F. McIntyre,David Walker,Suzanna M C Hardman,George C. Sutton,Theresa McDonagh,Martin R. Cowie +7 more
TL;DR: Early prognosis for incident (new) heart failure (HF) patients in the general population is poor and clinical trials suggest approximately half of chronic HF patients die suddenly but mode of death for incident HF cases in thegeneral population has not been evaluated.
Journal ArticleDOI
Diuretics in clinical practice. Part I: mechanisms of action, pharmacological effects and clinical indications of diuretic compounds.
TL;DR: This article discusses the mechanisms of action, pharmacological effects and clinical indications of the various diuretic classes used in everyday clinical practice, with emphasis on recent knowledge suggesting beneficial effects of certain diuretics on clinical conditions distinct from the traditional indications of these drugs.
References
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The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators.
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The Effect of Spironolactone on Morbidity and Mortality in Patients with Severe Heart Failure
Bertram Pitt,Faiez Zannad,Willem J. Remme,Robert J. Cody,Alain Castaigne,Alfonso Perez,Jolie Palensky,Janet Wittes +7 more
The effect of spironolactone on morbidity and mortality in patients with severe heart failure
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