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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Journal ArticleDOI
Mineralocorticoid Receptor Antagonism Attenuates Cardiac Hypertrophy and Failure in Low-Aldosterone Hypertensive Rats
Kohzo Nagata,Koji Obata,Jinglan Xu,Sahoko Ichihara,Akiko Noda,Hirotaka Kimata,Tomoko Kato,Hideo Izawa,Toyoaki Murohara,Mitsuhiro Yokota +9 more
TL;DR: Eplerenone attenuated both the decrease in the ratio of reduced to oxidized glutathione and the increase in NADPH oxidase activity apparent in DS-CHF rat hearts and resulted in attenuation of LV hypertrophy and failure, without an antihypertensive effect, in rats with low-aldosterone hypertension.
Journal ArticleDOI
Glucocorticoids Activate Cardiac Mineralocorticoid Receptors During Experimental Myocardial Infarction
Anastasia S. Mihailidou,Thi Yen Loan Le,Thi Yen Loan Le,Mahidi Mardini,Mahidi Mardini,Mahidi Mardini,John W. Funder +6 more
TL;DR: Spironolactone acts not merely by excluding corticosteroids from mineralocorticoid receptors but as a protective inverse agonist at low concentration, which may provide an additional therapeutic advantage in unstable angina and acute myocardial infarction.
Journal ArticleDOI
Evidence for Abnormal Left Ventricular Structure and Function in Normotensive Individuals with Familial Hyperaldosteronism Type I
Michael Stowasser,James E. Sharman,Rodel Leano,Richard D. Gordon,Gregory Ward,Diane Cowley,Thomas H. Marwick +6 more
TL;DR: Aldosterone excess is associated with increased left ventricular wall thicknesses and reduced diastolic function, even in the absence of hypertension.
Journal ArticleDOI
Aldosterone, Through Novel Signaling Proteins, Is a Fundamental Molecular Bridge Between the Genetic Defect and the Cardiac Phenotype of Hypertrophic Cardiomyopathy
Natalia Tsybouleva,Lianfeng Zhang,Suetnee Chen,Rajnikant Patel,Silvia Lutucuta,Shintaro Nemoto,Gilberto DeFreitas,Mark L. Entman,Blase A. Carabello,Robert Roberts,Ali J. Marian +10 more
TL;DR: The results implicate aldosterone as a major link between sarcomeric mutations and cardiac phenotype in HCM and signal the need for clinical studies to determine the potential beneficial effects of MR blockade in human HCM.
Journal ArticleDOI
Eplerenone in patients with systolic heart failure and mild symptoms: analysis of repeat hospitalizations.
Jennifer K. Rogers,John J.V. McMurray,Stuart J. Pocock,Faiez Zannad,Henry Krum,Dirk J. van Veldhuisen,Karl Swedberg,Harry Shi,John Vincent,Bertram Pitt +9 more
TL;DR: The Eplerenone in Mild Patients Hospitalization and SurvIval Study in Heart Failure (EMPHASIS-HF) trial as mentioned in this paper showed that the Eplrenone significantly reduced the risk of heart failure hospitalization in patients with mild symptoms to a greater extent than is captured by only studying the first hospitalization.
References
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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.
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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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