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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aldosterone plays an important role in the harmful cardiac remodeling process and pathophysiology of heart failure after a myocardial infarction. Until recently, spironolactone (Aldactone) was the only pharmacologic agent available to directly block the deleterious effects of aldosterone. The use of spironolactone is complicated by its antiprogesterone and antiandrogen side effects, such as gynecomastia and menstrual irregularities. Eplerenone (Inspra), a member of a new class of drugs called selective aldosterone receptor antagonists, was recently approved for the treatment of both hypertension and post-myocardial infarction heart failure and appears to be devoid of the antiprogesterone and antiandrogen effects. In a trial in patients with heart failure following a myocardial infarction, eplerenone treatment significantly reduced mortality and morbidity compared to placebo. Eplerenone may be considered as part of the therapeutic plan in patients who have suffered a myocardial infarction and demonstrate evidence of heart failure.
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PMID:New treatment option for heart failure patients: eplerenone. 1552 60

Eplerenone (Inspra) is a selective aldosterone blocker. Oral eplerenone is approved for use in patients with left ventricular (LV) systolic dysfunction and clinical evidence of heart failure following acute myocardial infarction (MI) in the US and in European countries (e.g. the UK and The Netherlands). The addition of eplerenone to standard medical therapy significantly improved mortality and morbidity in patients with LV systolic dysfunction and clinical evidence of heart failure following acute MI in the large, well designed EPHESUS (Eplerenone Post-acute myocardial infarction Heart failure Efficacy and SUrvival Study) trial. The beneficial effects of eplerenone on all-cause mortality and cardiovascular mortality were seen within 30 days of randomisation. Eplerenone was generally well tolerated. Although a higher incidence of hyperkalaemia occurred with eplerenone than with placebo, the incidence of hypokalaemia was significantly lower with eplerenone treatment. Thus, the addition of eplerenone to standard medical therapy is an important new strategy for further improving mortality and morbidity in post-MI patients with LV systolic dysfunction and heart failure.
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PMID:Eplerenone : a review of its use in left ventricular systolic dysfunction and heart failure after acute myocardial infarction. 1553 70

The two major outcome trials on the combination of angiotensin-converting enzyme (ACE) inhibitors and mineralocorticoid receptor (MR) antagonists in heart failure are RALES (Randomized Aldactone Evaluation Study) and EPHESUS (Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study). There have also been studies in essential hypertension, and in diabetic hypertensive patients, on the cardiac and renal effects of ACE inhibitors and MR antagonists, individually and in combination. In the clinical studies on heart failure, in outcome trials and the smaller studies using surrogate end points, a combination of ACE inhibition and MR blockade is superior to ACE inhibition alone, and in the hypertension studies to either agent alone. Some insight into their distinct sites of protective action may be gained from studies on experimental animal preparations. The principal caveat in the use of combination therapy is the possibility of hyperkalemia, which should be minimal in patients with creatine clearance greater than 30 mL/min and with the low doses of MR antagonist shown to be effective in outcome trials.
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PMID:ACE inhibitors and mineralocorticoid receptor blockade in patients with congestive heart failure. 1566 15

Eplerenone is a new aldosterone-receptor blocker that differs from spironolactone by virtue of higher selectivity for the aldosterone receptor. Therefore, eplerenone treatment is associated with comparative and absolute low incidences of gynecomastia, mastodynia, and abnormal vaginal bleeding. Similarly, a lower incidence of sexual impotence than that associated with spironolactone administration may be anticipated. Eplerenone and spironolactone increase natriuresis and cause renal retention of potassium when plasma aldosterone is high, i.e., both agents are facultative diuretics. Eplerenone reduces high blood pressure effectively. The results of a recent large study and an ensuing meta-analysis on antihypertensive treatment suggest that a diuretic should be the first-choice agent in most circumstances. Low-dose eplerenone combinations with a low-dose thiazide-type diuretic appear to be options worth investigating, since the overall cardiovascular benefit brought about by reducing blood pressure with the thiazide would be increased, inter alia, by the antikaliuretic action and by the blockade of extrarenal aldosterone receptors provoked by eplerenone. Eplerenone should replace spironolactone as a natriuretic and antikaliuretic in heart failure and as add-on treatment in severe systolic cardiac insufficiency, and it is indicated after an acute myocardial infarction complicated by left ventricular dysfunction and heart failure. The finding that hypertension control with diuretic-based pharmacotherapy results in better prevention of heart failure than pressure reduction with other drugs makes it pertinent to investigate whether diuretics in general, and eplerenone in particular, should constitute part of the initial pharmacotherapy for heart failure when there is no overt fluid retention and independent of the etiology. Eplerenone may cause hyperkalemia, and it might favor the development of metabolic acidosis or hyponatraemia in some circumstances.
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PMID:The aldosterone antagonist and facultative diuretic eplerenone: a critical review. 1573 14

The role of aldosterone-antagonists in the treatment of congestive heart failure. Despite the advances of the treatment of congestive heart failure, nearly half of the patients diagnosed with this disease five years ago are alive today. Experimental and human studies have demonstrated, that under special pathologic condition, the heart extracts aldosterone, and aldosterone extraction in the heart stimulates increased collagen turnover culminating in ventricular remodeling. Aldosterone blockade has been shown to be effective in reducing total mortality and hospitalization for heart failure in patients with systolic left ventricular dysfunction due to chronic heart failure (RALES study with spironolactone) and in patients with systolic left ventricular dysfunction post acute myocardial infarction (EPHESUS study with eplerenone). These clinical studies have shown that mineralocorticoid receptor activation remains important despite the use of angiotensin converting enzyme inhibitor or angiotensin receptor blocking agent and a beta blocker. In the ACC/AHA (and in the European and Hungarian) guidelines for the evolution and management of chronic heart failure, the indication of spironolactone was defined of Class Ila, Level of Evidence: B in CHF of stage C. The eplerenone (in US: INSPRA) was approved for the management of CHF patients after myocardial infarction with ejection fraction < 40%. Eplerenone, compared with spironolactone, is associated with a lower incidence of gynecomastia and other sex hormone-related adverse effect (breast pain, menstrual abnormalities). The spironolactone should not be used in patients with a creatinine above 220 mikromol/l. Despite the guidelines recommendation, spironolactone has been widely used in patients without consideration of their functional class or ejection fraction, without optimization of background treatment with ACE inhibitors and beta-blockers.
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PMID:[The role of aldosterone-antagonists in the treatment of congestive heart failure]. 1588 38

A dysregulation of the aldosterone system has been involved in the pathophysiology of cardiovascular diseases, including myocardial failure and, partially, essential hypertension. In humans and in rat models, aldosterone action induces heart remodeling and interstitial and perivascular myocardial fibrosis. Therefore, a rationale for using aldosterone antagonists (ARAs) of the spironolactone family, which have been available for decades for the treatment of aldosterone excess syndromes, has now emerged. The development of compounds such as eplerenone, with a greater selectivity for mineralocorticoid receptors, is promising also in terms of reduction of endocrine side effects. The use of ARAs for the treatment of myocardial failure and selected cases of hypertension, in combination with the current therapy, has been strongly supported by trials such as the Randomized Aldactone Evaluation Study (RALES) and the Eplerenone Neurohormonal Efficacy and Survival Study (EPHESUS). Thus, the addition of ARAs to the conventional therapy appears beneficial, leading to an improved survival rate and a reduced incidence of cardiac complications.
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PMID:Aldosterone receptor antagonists: biology and novel therapeutic applications. 1591 96

Spironolacotone and eplerenone are mineralocorticoid-blocking agents used for their ability to block both the epithelial and non-epithelial actions of aldosterone. Spironolactone is a non-selective mineralocorticoid receptor antagonist with moderate affinity for both progesterone and androgen receptors. The latter property increases the likelihood of endocrine side effects with spironolactone including loss of libido, menstrual irregularities, gynecomastia and impotence. Eplerenone is a next generation aldosterone receptor antagonist selective for aldosterone receptors alone. This lesser affinity for progesterone and androgen receptors was arrived at by replacing the 17-alpha -thioacetyl group of spironolactone with a carbomethoxy group. Eplerenone is further distinguished from spironolactone by its shorter half-life and the fact that it does not have any active metabolites. Both eplerenone and spironolactone are effective antihypertensive agents and each has been shown to improve the morbidity and mortality of heart failure. Eplerenone or spironolactone use can increase serum potassium values and occasionally results in clinically relevant hyperkalemia. This is more apt to occur with spironolactone due to the very long half-life of several of its active metabolites.
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PMID:Pharmacokinetics and pharmacodynamics of mineralocorticoid blocking agents and their effects on potassium homeostasis. 1594 88

Results of the Randomized Aldactone Evaluation Study and the Eplerenone Post-acute Myocardial Infarction Heart Failure Efficacy and Survival Study indicate aldosterone receptor antagonism, together with angiotensin-converting enzyme inhibition and loop diuretics, is a most effective strategy in reducing risk for all-cause and cardiovascular-related mortality and morbidity in patients with symptomatic heart failure. Responsible mechanisms are likely multifactoral. As a circulating hormone, aldosterone has well-known endocrine properties that contribute to the pathophysiology of congestive heart failure. This includes Na+ resorption at the expense of K+ excretion in such tissues as kidneys, colon, sweat, and salivary glands. Mg2+ excretion at these sites is likewise enhanced by aldosterone, whereas adrenal aldosterone secretion is regulated by extracellular Mg2+. Other endocrine actions of aldosterone receptor-ligand binding include: a reduction in biologically active cytosolic-free Mg2+, with intracellular Ca2+ loading in nonepithelial cells such as peripheral blood mononuclear cells; its influence on endothelial cell function; and its central actions, including the choroid plexus, activity of the hypothalamic paraventricular nucleus, and autonomic nervous system. De novo generation of aldosterone within the cardiovasculature is recognized and findings suggest its auto/paracrine properties contribute to tissue repair. Each of these actions is interrupted by aldosterone receptor antagonism and therefore may contribute to its salutary response in heart failure.
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PMID:Efficacy of aldosterone receptor antagonism in heart failure: potential mechanisms. 1603 25

Aldosterone produces adverse effects on the vasculature (endothelial dysfunction) and on the myocardium (myocardial fibrosis). These effects have adverse clinical consequences that result in increases in deaths caused by sudden death and by progressive heart failure. The Randomized Aldactone Evaluation Study and the Eplerenone Post-acute Myocardial Infarction Heart Failure Efficacy and Survival Study show this clearly. Aldosterone blockade should become a regular third neuroendocrine-blocking drug in patients with chronic heart failure.
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PMID:Aldosterone in heart failure: pathophysiology and treatment. 1603 41

Eplerenone is the second oral aldosterone antagonist available in the USA for the treatment of essential hypertension and heart failure. Treatment has been associated with reductions in blood pressure and improved survival (15% reduction in total mortality) for patients with heart failure who are in stable condition after a myocardial infarction. Due to the selectivity of eplerenone for the aldosterone receptor, adverse effects such as gynecomastia and vaginal bleeding seem to be less likely in patients who take eplerenone than in those who take spironolactone. The most severe side effect of spironolactone, hyperkalemia, was also observed with eplerenone. 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. The American College of Cardiology recommends trying spironolactone first and then switching to eplerenone if patients develop gynecomastia, menstrual irregularities, or impotence.
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PMID:Eplerenone (Inspra), a new aldosterone antagonist for the treatment of systemic hypertension and heart failure. 1620 Jan 4


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