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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Mineralocorticoids in the Heart and Vasculature: New Insights for Old Hormones
TL;DR: Interference with the interaction between MR and its coregulators seems to be a promising strategy toward the development of selective MR modulators.
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Mineralocorticoid receptor blockade but not steroid withdrawal reverses renal fibrosis in deoxycorticosterone/salt rats.
TL;DR: It is hypothesize that continuing tubular inflammation and fibrosis despite DOC withdrawal indicates that the renal tissue may reflect MR activation in the context of tissue damage.
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Eplerenone (Inspra), a new aldosterone antagonist for the treatment of systemic hypertension and heart failure.
TL;DR: While eplerenone is more selective, with the potential for fewer side effects, its overall efficacy has not been proven to be superior to that of spironolactone in clinical trials.
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Role of Aldosterone and Mineralocorticoid Receptor in Cardiovascular Aging.
Stefania Gorini,Seung Kyum Kim,Seung Kyum Kim,Marco Infante,Caterina Mammi,Sandro La Vignera,Andrea Fabbri,Iris Z. Jaffe,Massimiliano Caprio +8 more
TL;DR: There is an unmet need for the enhanced understanding of the role of MR in aging and for development of novel specific MR antagonists in the context of cardiovascular rehabilitation in the elderly, in order to reduce relevant side effects.
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Peripheral artery disease and outcomes after myocardial infarction: An individual-patient meta-analysis of 28,771 patients in CAPRICORN, EPEHESUS, OPTIMAAL and VALIANT
Sally C. Inglis,Judith Bebchuk,Sultan A. Al-Suhaim,Jessica Case,Marc A. Pfeffer,Scott D. Solomon,Yingxin Rachel Hou,Bertram Pitt,Henry J. Dargie,Ian Ford,John Kjekshus,Faiez Zannad,Kenneth Dickstein,John J.V. McMurray +13 more
TL;DR: PAD is common and is an independent predictor of worse outcomes in patients already at high risk after MI because of left ventricular systolic dysfunction, heart failure or both, and represents an important group for intensive application of secondary preventive therapies.
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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