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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eplerenone, a selective mineralocorticoid receptor antagonist currently approved by the Food and Drug Administration for treatment of hypertension, reduces mortality following myocardial infarction in patients with left ventricular dysfunction and clinical signs of congestive heart failure. Previous research by the same group established that spironolactone does the same at lower cost than eplerenone.
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PMID:Selective aldosterone blockade reduces mortality after MI. 1266 99

Diagnosis of primary aldosteronism results in either the surgical cure of hypertension or targeted pharmacotherapy. The two major subtypes of primary aldosteronism are unilateral aldosterone-producing adenoma (APA) and bilateral idiopathic hyperaldosteronism (IHA). Patients with APA usually are treated with unilateral adrenalectomy and patients with IHA are treated medically. The majority of patients with primary aldosteronism have the IHA subtype and require pharmacotherapy. Spironolactone has been the drug of choice to treat primary aldosteronism. However, it is not selective for the aldosterone receptor, and side effects include gynecomastia, erectile dysfunction and menstrual irregularity. Eplerenone is a new competitive and selective aldosterone receptor antagonist recently approved by the United States Food and Drug Administration for the treatment of hypertension. It lacks the side effects associated with spironolactone and will be the superior drug if it is shown to be as effective as spironolactone for the treatment of mineralocorticoid-dependent hypertension.
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PMID:Primary aldosteronism - treatment options. 1291 36

Recent studies suggest that aldosterone may play a larger role than once appreciated in normal physiologic function and cardiovascular disease. Some of the adverse cardiovascular effects that have been described include cardiac and vascular fibrosis, vascular necrosis and inflammation, impaired endothelial function, reduced fibrinolysis, hypertension, left ventricular hypertrophy (LVH), congestive heart failure, and cardiac arrhythmias. In light of these findings, the ability to block the actions of aldosterone has gained increased therapeutic importance. Eplerenone is a selective aldosterone receptor blocker that displays little interaction with androgen and progesterone receptors. Eplerenone has already been approved for the treatment of systemic hypertension and has been evaluated in numerous hypertension subgroups, including patients with low plasma renin activity; diabetes; LVH; uncontrolled blood pressure while receiving monotherapy with angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, calcium channel blockers, or beta-blockers; and in black patients. Results of these trials indicate that eplerenone lowers blood pressure and reduces end-organ damage. Further proof of the therapeutic importance of mineralocorticoid receptor blockade comes from the eplerenone post acute myocardial infarction survival and efficacy study (EPHESUS). In this large-scale clinical outcome trial, eplerenone was shown to reduce total mortality by 15% as well as the combined endpoint of cardiovascular mortality/cardiovascular hospitalization by 13% when administered at a mean of 7.3 days post myocardial infarction to patients with evidence of systolic left ventricular dysfunction and symptoms of heart failure. Eplerenone is well tolerated, with an adverse effect profile comparable to placebo. The advent of selective aldosterone blockers, such as eplerenone, should prove to be of great therapeutic value in hypertension control and prevention of cardiovascular disease and associated end-organ damage.
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PMID:Eplerenone: a selective aldosterone blocker. 1293 Dec 52

Aldosterone is an important and independent target for therapeutic intervention in hypertension and hypertension-related diseases. Its actions, once thought to be limited to the distal convoluted tubule of the kidney, are now recognised to be wide-ranging, including interactions with mineralocorticoid receptors in diverse cardiovascular sites to mediate vascular and myocardial remodelling and dysfunction. The latter are referred as non-epithelial actions. Spironolactone, an aldosterone receptor antagonist, is indicated for the treatment of mineralocorticoid hypertension, but its use is limited by an adverse effect profile that includes not only by hyperkalaemia, but also antiandrogenic and progestational effects resulting from its poor specificity for the aldosterone receptor. Eplerenone is the first selective aldosterone receptor antagonist to be developed and recently gained approval from the US FDA for treatment of systemic hypertension. This was based on studies which demonstrated that eplerenone had a blood pressure-lowering profile that was equivalent to existing antihypertensive agents, was useful for treatment of low-renin and systolic hypertension, maintained utility even as add-on therapy to other antihypertensive agents, and exerted beneficial effects on hypertension-related left ventricular hypertrophy and renal impairment. Perhaps most notably, eplerenone was generally well tolerated, and did not cause the antiandrogenic and progestational adverse effects commonly observed with spironolactone.
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PMID:Aldosterone receptor antagonists for hypertension: what do they offer? 1296 13

Aldosterone has been implicated for many years as an important substance in the pathogenesis of heart disease. Elevated aldosterone concentrations have been documented in patients with hypertension and heart failure, leading to the use of aldosterone antagonists for the treatment of these conditions. Spironolactone has been used for nearly 2 decades for the treatment of hypertension, and more recently, has become a standard agent for the treatment of systolic heart failure. Spironolactone, however, is a nonselective antagonist of the aldosterone receptor, binding also to other steroid receptors and causing a significant percentage of patients to have sex hormone-related adverse effects such as gynecomastia. Eplerenone is the first of a new class of drugs known as selective aldosterone receptor antagonists, which selectively block the aldosterone receptor with minimal effect at other steroid receptors, thereby minimizing many of the hormonal side effects seen with spironolactone. Eplerenone has been shown to be beneficial both as monotherapy and combination therapy for lowering elevated blood pressure in patients with hypertension. The antihypertensive efficacy of eplerenone is roughly similar to that of other antihypertensive agents, although in 1 study black patients responded better with eplerenone than losartan. In addition, eplerenone has demonstrated some renoprotective effects in diabetic patients with hypertension. Recently, eplerenone was shown to significantly reduce mortality and cardiovascular morbidity in post-myocardial infarction patients with systolic heart failure currently taking standard heart failure medications. Eplerenone is generally well tolerated, although hyperkalemia with this agent is of some concern. Eplerenone is metabolized by CYP3A4 and administration with potent inhibitors of this enzyme is contraindicated because of the risk of hyperkalemia. In summary, eplerenone has proven to be beneficial in treating hypertension and post-myocardial infarction heart failure. Its exact place in therapy will in large part be determined by its cost and whether or not future studies will be able to demonstrate a clinical benefit of this agent over spironolactone or other currently available treatments.
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PMID:Eplerenone: a selective aldosterone receptor antagonist for hypertension and heart failure. 1450 34

In most countries the last two decades have seen a very substantial rise in the prevalence of heart failure, and in a majority of patients hypertension is both an antecedent condition and a contributing cause. Heart failure is also a major cause of hospital admissions; its amelioration and, as far as possible, prevention is therefore important in terms not only of morbidity and premature mortality for the individual patient, but also containment of healthcare costs. Over the past 5 years, mineralocorticoid receptor (MR) antagonists have been used in two major outcome trials (the Randomized Aldactone Evaluation Study [RALES] with spironolactone, and the Eplerenone Post-AMI Heart Failure Efficacy and Survival Study [EPHESUS]), in severe (New York Heart Association class III) and post-myocardial infarct heart failure, respectively. Experimental studies have largely focused, however, on various animal models of hypertension; on the basis of a portfolio of clinical studies on the efficacy of eplerenone, administered either alone and in combination as an antihypertensive agent, the novel MR antagonist was approved by the FDA for the treatment of hypertension, though it has yet to be launched. In this review, the two major outcome studies (RALES, EPHESUS) are discussed in the context of the new biology of aldosterone action. The relevance to heart failure of current experimental studies, largely on vascular protection, will also be discussed.
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PMID:The role of mineralocorticoid receptor antagonists in the treatment of cardiac failure. 1464 Sep 40

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

This study compared the efficacy and tolerability of eplerenone and enalapril in 499 patients with stage 1 or 2 hypertension who were randomized to receive eplerenone or enalapril for 6 months in a 3-step titration-to-effect study. After 6 months, patients whose diastolic blood pressure (BP) was <90 mm Hg had their dosages down-titrated were followed for an additional 6 months. Diastolic BP was the primary end point. Eplerenone was as effective as enalapril in reducing both systolic BP (eplerenone, -14.5 mm Hg; enalapril, -12.7 mm Hg; p = 0.199) and diastolic BP (eplerenone, -11.2 mm Hg; enalapril, -11.3 mm Hg; p = 0.910) at 6 months. BP reductions at 12 months were also similar between groups (-16.5/-13.3 mm Hg for eplerenone, -14.8/-14.1 mm Hg for enalapril; p = 0.251 and 0.331, respectively). Withdrawal rates for adverse events (eplerenone 7.9%, enalapril 9.3% at 6 months) and treatment failures (eplerenone 23.3%, enalapril 22.8% at 6 months) were also equivalent. Approximately 2/3 of each group had normal BP with monotherapy treatment at 6 months. BP response was independent of renin levels in the eplerenone group, but not in the enalapril group. Both agents reduced albuminuria in patients who had an elevated value at baseline, with significantly greater improvement in patients treated with eplerenone versus enalapril (-61.5% vs -25.7%; p = 0.01). Both agents were similarly well tolerated, and there was no increased incidence of any sexual adverse events in the eplerenone group. Patients taking enalapril had a higher rate of cough. Both agents increased serum potassium levels, but <1% in each group reported adverse events from hyperkalemia. Eplerenone was as effective as enalapril as monotherapy in patients with stage 1 or 2 hypertension, was more effective in reducing albuminuria, and was well tolerated for 12 months.
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PMID:Efficacy of eplerenone versus enalapril as monotherapy in systemic hypertension. 1508 41

We examined the effect of different levels of salt intake on the role of aldosterone on cardiac and vascular changes in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP). Eleven-week-old SHRSP were fed high-salt (4.2% NaCl), normal-salt (0.28%), or low-salt (0.03%) diets with or without eplerenone (100 mg/kg per day, in food) for 5 weeks. A group of high-salt SHRSP was also treated with hydralazine (25 mg/kg per day). Blood pressure increased more in high-salt rats than in other groups (P<0.001). Eplerenone prevented further blood pressure rise in salt-loaded rats, with little effect on control and low-salt SHRSP. Increased media-to-lumen ratio of mesenteric resistance arteries induced by salt (P<0.01) was prevented by eplerenone (P<0.01). Maximal acetylcholine-induced vasodilation was impaired under salt loading (P<0.01), but improved under eplerenone (P<0.01). Eplerenone prevented (P<0.01) increased heart weight and left and right ventricular collagen deposition induced by high salt. Blood pressure lowering by hydralazine in high-salt SHRSP did not influence endothelial function or left ventricular collagen. Our study demonstrates salt-dependency of aldosterone effects on severity of hypertension, endothelial dysfunction, and cardiac and vascular remodeling in SHRSP. These effects were attenuated by eplerenone, particularly in the salt-loaded state, underlining the pathophysiological role of aldosterone in salt-sensitive hypertension.
Hypertension 2004 Jun
PMID:Eplerenone prevents salt-induced vascular remodeling and cardiac fibrosis in stroke-prone spontaneously hypertensive rats. 1511 13

Aldosterone mediates both water and electrolyte balance by acting on the renal mineralocorticoid receptors. Recent experimental studies have also documented the presence of these receptors in other body organs, including the brain, blood vessels, and heart, suggesting that aldosterone plays a larger role in normal physiologic function and in cardiovascular diseases such as systemic hypertension and congestive heart failure (CHF). The nonspecific aldosterone inhibitor spironolactone, and the selective aldosterone inhibitor eplerenone, are both approved for clinical use in treating patients with hypertension and/or symptomatic CHF. Studies have shown that spironolactone lowers blood pressure, improves endothelial function, reduces myocardial hypertrophy and fibrosis, and lowers the incidence of fatal arrhythmias. Eplerenone, which is more specific for the mineralocorticoid receptor, appears to provide all the beneficial effects of spironolactone in hypertensive patients, with the potential to modify many of the side effects related to nonspecific steroid-receptor blockade. Hyperkalemia remains a potential problem with all aldosterone antagonists.
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PMID:Aldosterone and aldosterone antagonism in systemic hypertension. 1512 71


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