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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A double-blind randomized multicentre clinical trial to evaluate the efficacy and safety of two doses of etomoxir in comparison with placebo in patients with moderate congestive heart failure: the ERGO (etomoxir for the recovery of glucose oxidation) study.
Christian Holubarsch,Martin Rohrbach,Matthias Karrasch,Erich Boehm,Lech Poloński,Piotr Ponikowski,Siegfried Rhein +6 more
TL;DR: The number of patients that completed the ERGO study was too small to demonstrate significant effects on exercise time, although there was a tendency towards an increase in exercise time.
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Mineralocorticoid receptors: distribution and activation.
TL;DR: Cortisol changes from an MR antagonist to an MR agonist when intracellular redox state is changed—by inhibition of 11β HSD2, generation of reactive oxygen species, or intrace cellular introduction of oxidised glutathione (GSSG)—cortisol appears to underlie the therapeutic efficacy of MR blockade in heart failure and in essential hypertension.
Journal ArticleDOI
The renin-angiotensin-aldosterone system and its suppression.
TL;DR: This review focuses on updates in the understanding of the RAAS and the pathophysiology of AngII and aldosterone excess, reviewing what is known about its suppression in cardiovascular and renal diseases, especially in the cat and dog.
Journal ArticleDOI
A double-blind, randomized study comparing the antihypertensive effect of eplerenone and spironolactone in patients with hypertension and evidence of primary aldosteronism.
Hari K Parthasarathy,Joël Ménard,William B. White,William F. Young,Gordon H. Williams,Bryan Williams,Luis M. Ruilope,Gordon T. McInnes,John M. C. Connell,Thomas M. MacDonald +9 more
TL;DR: The antihypertensive effect of spironolactone was significantly greater than that of eplerenone in hypertension associated with primary aldosteronism.
Journal ArticleDOI
Safety and Efficacy of Eplerenone in Patients at High Risk for Hyperkalemia and/or Worsening Renal Function : Analyses of the EMPHASIS-HF Study Subgroups (Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure)
Romain Eschalier,John J.V. McMurray,John J.V. McMurray,Karl Swedberg,Dirk J. van Veldhuisen,Henry Krum,Stuart J. Pocock,Harry Shi,John Vincent,Patrick Rossignol,Faiez Zannad,Bertram Pitt,Emphasis-Hf Investigators +12 more
TL;DR: In patients with chronic HF-REF, in NYHA functional class II, and meeting specific inclusion and exclusion criteria, eplerenone was both efficacious and safe when carefully monitored, even in subgroups at high risk of developing hyperkalemia or WRF.
References
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Donald W. Cockcroft,M H Gault +1 more
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).
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The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators.
Bertram Pitt,Faiez Zannad,Willem J. Remme,Robert J. Cody,Alain Castaigne,Alfonso Perez,Jolie Palensky,Janet Wittes +7 more
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
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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