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Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eplerenone is a highly selective aldosterone blocking agent, which was recently approved for the treatment of hypertension and has also been shown to reduce mortality in post-myocardial infarction patients with heart failure. To assess its usefulness in patients with essential hypertension, we performed a 12-week, double-blind, placebo-controlled, parallel-arm, fixed-dose study over a range of doses using clinic and ambulatory blood pressure (BP). After single-blind placebo therapy for 3 to 4 weeks to obtain baseline measures, 400 patients were randomized to receive placebo or 1 of 4 doses of eplerenone (25, 50, 100, and 200 mg once daily). In addition, changes from baseline in serum potassium, active renin activity, and serum aldosterone were assessed. After 12 weeks of therapy, reductions in clinic BP showed a significant dose response in which 25 mg of eplerenone achieved statistical significance compared with placebo for systolic BP; maximum clinic BP reduction was achieved with the 100 mg dose. Ambulatory BP monitoring showed that all doses of eplerenone (25 to 200 mg/day) lowered BP significantly greater than placebo with a significant dose response. The 24-hour mean BP reductions ranged from 6.4/4.4 to 10.3/5.7 mm Hg on eplerenone compared with 1.3/0.8 mm Hg on placebo. One patient on placebo and 1 patient on 200 mg of eplerenone had episodes of elevated serum potassium levels (>5.5 mEq/L). Increases in serum aldosterone were related to dose but not to reductions in 24-hour BP. Side effects and withdrawal rates attributed to eplerenone were similar to those of placebo. These data show that eplerenone is an effective antihypertensive agent at doses as low as 25 mg/day. The top effective dose in stage 1 to 3 hypertension based on clinic and ambulatory BP was 100 mg once daily. The incidence of elevated serum potassium levels was not increased across doses of eplerenone in this study.
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PMID:Assessment of the novel selective aldosterone blocker eplerenone using ambulatory and clinical blood pressure in patients with systemic hypertension. 1284 42

Approximately 40% of Japanese patients with essential hypertension, including low-renin hypertension, are inadequately managed. Low-renin hypertension generally responds poorly to angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers, but may respond more optimally to diuretics, calcium channel blockers, and aldosterone blockers. This multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study evaluated the efficacy and safety of the selective aldosterone blocker eplerenone in 193 Japanese patients with essential hypertension. Although not a study inclusion criterion, baseline active plasma renin levels were consistently low (5.7-10.1 mU/L); most patients met the criteria for low-renin hypertension (< or =42.5 mU/L; normal range, 7-76 mU/L). Patients received placebo or eplerenone 50, 100, or 200 mg once daily for 8 weeks. Systolic blood pressure decreased significantly (-6.8 to -10.6 mm Hg vs. -2.1 mm Hg; p< or =0.0022 vs. placebo). Eplerenone offers significant blood pressure reduction with good tolerability in Japanese patients with hypertension, including those with low-renin hypertension.
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PMID:Efficacy and safety of the selective aldosterone blocker eplerenone in Japanese patients with hypertension: a randomized, double-blind, placebo-controlled, dose-ranging study. 1507 71

Eplerenone is a selective aldosterone blocker (SAB) approved for the treatment of essential hypertension. Oral eplerenone reduced BP effectively in patients with essential hypertension, both as monotherapy and in combination with other agents. The drug is generally well tolerated; the risk of hyperkalemia can be managed through careful selection and monitoring of patients. Preliminary data suggest that treatment of hypertension with eplerenone may provide protective effects against end-organ disease; further work is needed to elucidate the clinical significance of these findings, and to evaluate the outcome of treatment of hypertension in terms of cardiovascular morbidity and mortality and quality of life. In the meantime, as the first SAB to become available, eplerenone is an interesting addition to the drugs currently available for the treatment of hypertension.
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PMID:Eplerenone: a review of its use in essential hypertension. 1563 38

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

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

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

Recent interest in mineralocorticoid receptor (MR) antagonism in cardiovascular disease reflects recognition that blockade of the renin-angiotensin system may be followed by a breakthrough in aldosterone levels to or above the normal range. The Randomized Aldactone Evaluation Study (RALES) trial in progressive heart failure, Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) in post-infarct heart failure, and the 4E trial in essential hypertension demonstrated the efficacy of MR blockade in addition to standard therapy. In all three trials, plasma aldosterone levels were low and sodium status unremarkable; this finding, and those of various preclinical studies, point squarely at pathophysiological MR activation by ligands other than aldosterone, most likely normal levels of cortisol, and provide clear evidence for the therapeutic utility of MR blockade in conditions of tissue and organ damage with normal aldosterone levels.
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PMID:Eplerenone: hypertension, heart failure and the importance of mineralocorticoid receptor blockade. 1980 89

Eplerenone, a selective aldosterone blocker, has become clinically available in Japan since 2007. It has been reported that eplerenone has a potential antihypertensive effect, with a profile slightly different from that of spironolactone, and has fewer adverse reactions, suggesting that it may become a first-line treatment for hypertension. However, clinical data on hypertensive patients in Japan are lacking for eplerenone. In this study, we explored the clinical efficacy of eplerenone when it is added to an angiotensin-converting enzyme (ACE) inhibitor or a long-acting calcium channel blocker (CCB) in 68 (31 males, 37 females) Japanese patients with essential hypertension. After adding 50 mg of eplerenone to their basal treatment, blood pressure was significantly reduced at 4 weeks, and further reduced after 24 weeks of eplerenone treatment. Urinary albumin excretion decreased significantly after 24 weeks. There were no significant differences in general biochemical test values or electrolytes, but fasting serum triglycerides were significantly decreased after eplerenone treatment. The serum potassium level showed no significant change during treatment. There were no significant correlations between plasma renin activity or plasma aldosterone concentration (PAC) before eplerenone treatment and blood pressure after eplerenone treatment, showing that the antihypertensive effect of eplerenone is not affected by the patient's renin profile or pretreatment PAC values. Eplerenone was also effective in hypertensive patients with metabolic syndrome. In conclusion, eplerenone, when coadministered with an ACE inhibitor or a long-acting CCB, caused an extremely beneficial antihypertensive effect in Japanese patients with essential hypertension, without few clinically important adverse events.
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PMID:Clinical effects of eplerenone, a selective aldosterone blocker, in Japanese patients with essential hypertension. 1986 6

Hypertension is associated with endothelial dysfunction and activated Rho-associated kinases (ROCKs). The purpose of this study was to evaluate the effects of the selective mineralocorticoid receptor blocker, eplerenone, on endothelial function and ROCK activity in patients with hypertension. The study was carried out over 48 weeks in 60 untreated patients with hypertension who were randomly assigned to eplerenone, nifedipine, and losartan groups. We evaluated the effects of each treatment on flow-mediated vasodilation (FMD) and ROCK activity in peripheral leukocytes. Eplerenone increased FMD and decreased leukocyte ROCK activity. Nifedipine decreased ROCK activity but did not alter FMD. Losartan increased FMD but did not alter ROCK activity. Hypotensive effects were similar in the three groups, as was nitroglycerin-induced vasodilation during the follow-up period. There were no significant differences between the groups with respect to other parameters. The study results show that eplerenone improves endothelial function and inhibits ROCK activity in patients with essential hypertension.
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PMID:Mineralocorticoid receptor blocker eplerenone improves endothelial function and inhibits Rho-associated kinase activity in patients with hypertension. 2220 91

Primary hyperaldosteronism (PHA) is characterized by an increased Aldosterone synthesis which is independent of the Renin-Angiotensin-Aldosterone-System (RAAS). The prevalence of PHA in patients who present in specialized hypertension centers is approx. 10 %. Besides patients with the classical symptoms known as "Conn-Trias" (hypertension, hypokalemia, metabolic alkalosis), the more frequent normokalemic patients with PHA also show a worse outcome compared to patients with essential hypertension. Identifying these patients is an important task in the evaluation of hypertension since targeted treatment options are available. Screening for PHA using the Aldosterone-Renin-Ratio (ARR) should be performed in patients with hypokalemic, severe or resistant hypertension. In addition, young patients with early onset of severe hypertension and/or positive family history should be screened. A positive screening result should be followed by a confirmatory test. The saline infusion test is the preferred clinical test for confirming a suspected PHA since it is accessible and time efficient. Other confirmatory tests are not used on a regular basis. After any confirmatory test, CT- or MRI-imaging and adrenal vein sampling (AVS) is used in order to differentiate between a unilateral adenoma, a bilateral hyperplasia or another cause of PHA. CT or MRI usually cannot discriminate smaller tumors form hyperplasia. Therefore AVS is used to detect lateralization of autonomous aldosterone production. Lateralization of aldosterone production indicates a unilateral adenoma. In these cases, laparoscopic adrenalectomy is the therapeutic option of choice with a hypertension cure rate of up to 60 %. If no lateralization is detectable, bilateral hyperplasia as the underlying cause of PHA is likely. Pharmacological inhibition of the mineralocorticoid receptor is the preferred treatment option in these cases. If Spironolactone is not well tolerated, Eplerenone and potassium-sparing diuretics should be prescribed. Often, however, in order to fully control hypertension, additional antihypertensive therapy is necessary.
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PMID:[Primay hyperaldosteronism--diagnostic and treatment]. 2316 80


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