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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Primary and Secondary Prevention of Cardiovascular Diseases: A Practical Evidence-Based Approach
TL;DR: Therapeutic lifestyle changes in conjunction with an aggressive multidrug regimen targeted toward the normalization of the major CV risk factors will neutralize the atherogenic milieu, reduce vascular inflammation, and markedly decrease the risk of adverse CV events and need for revascularization procedures.
Journal ArticleDOI
Aldosterone induces superoxide generation via Rac1 activation in endothelial cells.
TL;DR: The present study is the first to demonstrate that aldosterone induces superoxide generation via mineralocorticoid receptor-mediated activation of NAD(P)H-oxidase and Rac1 in endothelial cells, thereby contributing to the development of ald testosterone-induced vascular injury.
Journal ArticleDOI
Novel RAAS agonists and antagonists: clinical applications and controversies
TL;DR: The present and future pharmacological manipulation of this important system is summarized and other potential therapeutic targets emerge, which could provide improved cardiovascular and renal protection beyond that provided by an ACE inhibitor or ARB.
Journal ArticleDOI
Changing characteristics and mode of death associated with chronic heart failure caused by left ventricular systolic dysfunction: a study across therapeutic eras.
Richard M Cubbon,Chris Gale,Lorraine C Kearney,Clyde B. Schechter,W Paul Brooksby,James Nolan,Keith A.A. Fox,Adil Rajwani,Wazir Baig,David Groves,Pauline E. Barlow,Anthony C. Fisher,P D Batin,Matthew Kahn,Azfar Zaman,Ajay M. Shah,Jon A. Byrne,Steven Lindsay,Robert J. Sapsford,Stephen B. Wheatcroft,Klaus K. Witte,Mark T. Kearney +21 more
TL;DR: In this paper, a comparison of two prospective cohort studies of outpatients with chronic heart failure caused by left ventricular systolic dysfunction performed between 1993 and 1995 (historic cohort: n=281) and 2006 and 2009 (contemporary cohort, n=357).
Journal ArticleDOI
Aldosteronism and Peripheral Blood Mononuclear Cell Activation: A Neuroendocrine-Immune Interface
Robert A. Ahokas,Kenneth J. Warrington,Ivan C. Gerling,Yao Sun,Linus A. Wodi,P. A. Herring,Li Lu,Syamal K. Bhattacharya,Arnold E. Postlethwaite,Karl T. Weber +9 more
TL;DR: AlDO receptor antagonism modulates this neuroendocrine-immune interface and is associated with an activation of circulating immune cells induced by iterations in PBMC divalent cations and transduced by oxidative/nitrosative stress.
References
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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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