eplerenone and Hypertrophy--Left-Ventricular

In this article, we review the evidence supporting the use of eplerenone for improving cardiovascular prognosis. Activation of the renin-angiotensin-aldosterone system plays a major role in the pathogenesis of heart disease, and blockage of this system has been shown to improve prognosis in several cardiovascular conditions. The 2 marketed aldosterone antagonists, spironolactone and eplerenone, improve prognosis in patients with left ventricular (LV) dysfunction and are effective antihypertensive medications. In addition, a potential role for aldosterone antagonists in the treatment of patients with heart failure and preserved LV function has been suggested and is currently being evaluated in clinical trials. In patients with myocardial infarction having LV dysfunction and evidence of heart failure, eplerenone improves cardiovascular outcomes and attenuates myocardial remodeling. In addition, eplerenone is effective for the treatment of hypertension, where it regresses both LV hypertrophy and proteinuria (2 powerful markers of increased cardiovascular risk). In contrast to spironolactone, eplerenone essentially lacks the sexual side effects that sometimes limit the use of spironolactone. Hyperkalemia is the main potential side effect of eplerenone, especially when used in combination with other medications that can cause hyperkalemia. Adequate patient selection and monitoring are therefore of utmost importance when using this medication. In conclusion, eplerenone is a medication that offers the cardiovascular therapeutic and prognostic benefits of aldosterone antagonism but with fewer side effects compared to spironolactone.

Topics: Cardiovascular Diseases; Eplerenone; Heart Failure; Humans; Hyperkalemia; Hypertension; Hypertrophy, Left Ventricular; Mineralocorticoid Receptor Antagonists; Myocardial Infarction; Prognosis; Renin-Angiotensin System; Risk; Spironolactone; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Remodeling

The role of the renin-angiotensin-aldosterone system (RAAS) in hypertension has since long been recognized and aldosterone has been acknowledged as one of the key hormones in the pathophysiology, not only in primary aldosteronism but also in essential hypertension and drug-resistant hypertension. Aldosterone-receptor antagonists (ARAs) are increasingly used in patients with resistant hypertension, often with impressive results. However, definitive evidence for the benefit of ARAs in these patients from randomized, controlled trials is lacking. This review gives an overview of the current data on this topic. Future studies should focus on the identification of factors that are able to predict the response to treatment, as to select patients who will benefit most from treatment with ARAs. On the basis of the current knowledge, we recommend prescription of ARAs to patients with primary aldosteronism, resistant hypertension and patients with hypertension and hypokalemia.

Topics: Albuminuria; Aldosterone; Angiotensin-Converting Enzyme Inhibitors; Animals; Arrhythmias, Cardiac; Drug Therapy, Combination; Electrocardiography; Eplerenone; Fibrosis; Glomerular Filtration Rate; Humans; Hypertension; Hypertrophy, Left Ventricular; Mineralocorticoid Receptor Antagonists; Myocardium; Spironolactone

Accumulating evidence indicates that aldosterone is involved in cardiovascular disease by inducing inflammation in the presence of moderate amounts of salt in the diet. Spironolactone and eplerenone are the mineralocorticoid receptor (MR) antagonists currently available for the treatment of hypertension. They have similar safety and antihypertensive efficacy. The advantage of eplerenone is the lower incidence of anti-androgenic and progestational side effects. The rationale for using MR blockade in the treatment of hypertension is threefold: the evidence of antihypertensive efficacy, the phenomenon of "aldosterone escape" occurring with angiotensin-converting enzyme inhibitor and angiotensin-receptor blockade therapy, and the compelling evidence that MR antagonism reduces target-organ damage in hypertensive patients and improves survival in patients with cardiovascular disease. Thus, blockade of the MR may be very useful in many patients with hypertension, particularly those at risk for or having evidence of target-organ damage.

Topics: Albuminuria; Aldosterone; Animals; Drug Therapy, Combination; Eplerenone; Humans; Hyperkalemia; Hypertension; Hypertrophy, Left Ventricular; Mineralocorticoid Receptor Antagonists; Renin-Angiotensin System; Spironolactone; Vasodilation

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.

Topics: Animals; Clinical Trials as Topic; Eplerenone; Heart Failure; Humans; Hypertension; Hypertrophy, Left Ventricular; Mineralocorticoid Receptor Antagonists; Spironolactone

The role of the renin-angiotensin-aldosterone system in the pathophysiology and treatment of hypertension and heart failure has been extensively studied. Angiotensin-converting enzyme inhibitors and angiotensin II-receptor blockers have been shown to effectively reduce blood pressure, protect the kidney, and reduce morbidity and mortality in patients with heart failure. Therefore, there is increased interest in the effects of aldosterone and the use of aldosterone-receptor antagonists in the treatment of cardiovascular disease. Eplerenone is the first selective aldosterone-receptor antagonist approved for the treatment of hypertension and left ventricular (LV) dysfunction after acute myocardial infarction (AMI).. The goal of this article was to review the pharmacologic properties, clinical efficacy, and tolerability of eplerenone in the treatment of hypertension, LV dysfunction, and proteinuria.. Relevant English-language articles were identified through searches of MEDLINE (1966-May 2003), Current Contents, and International Pharmaceutical Abstracts (1970-May 2003) using the terms hypertension, heart failure, eplerenone, aldosterone, and aldosterone antagonist. Other pertinent publications were identified from the reference lists of the identified articles. Information was also obtained from abstracts presented at national meetings and data on file with the manufacturer.. In clinical trials, eplerenone alone and in combination with renin-angiotensin blockade significantly reduced both systolic and diastolic blood pressure compared with placebo (P < 0.05 to P < 0.001). In EPHESUS (Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study), the addition eplerenone to optimal medical therapy reduced morbidity and mortality in patients with AMI and LV dysfunction, although the incidence of serious hyperkalemia was also significantly greater. In comparisons with spironolactone, eplerenone was associated with a lower incidence of gynecomastia and other sex hormone-related adverse effects.. Either alone or in combination with other antihypertensive agents, eplerenone appears to be effective for the treatment of hypertension. Morbidity and mortality were reduced when eplerenone was added to standard therapy for LV dysfunction complicating AMI. The use of eplerenone for hypertension or heart failure may be limited in patients at risk for hyperkalemia.

Topics: Area Under Curve; Clinical Trials as Topic; Drug Interactions; Eplerenone; Humans; Hyperkalemia; Hypertension; Hypertrophy, Left Ventricular; Mineralocorticoid Receptor Antagonists; Proteinuria; Spironolactone; Ventricular Dysfunction, Left

Mineralocorticoid receptor antagonists are increasingly used in patients with treatment-resistant hypertension (TRH). There is experimental evidence for blood pressure (BP) independent effects of mineralocorticoid receptor blockade on cardiovascular target organ damage. We hypothesized that low-dose eplerenone (50 mg) will reduce left ventricular mass (LVM) beyond its BP-lowering effects.. We performed a randomized, double-blind, placebo-controlled, parallel group study in 51 patients with TRH. Patients were allocated to receive either eplerenone 50 mg or placebo for 6 months, while other antihypertensive agents could be added in both groups to achieve a BP target of less than 140/90 mmHg. LVM was assessed by MRI before and after treatment.. Baseline office BP was similar in the eplerenone and the placebo group (166 ± 21/91 ± 15 versus 159 ± 19/94 ± 8 mmHg, n.s.). BP was similarly reduced in the eplerenone versus the placebo group (-35 ± 20/-15 ± 11 versus -30 ± 19/-13 ± 7 mmHg, n.s.). However, LVM was reduced only in the eplerenone group (from 155 ± 33 to 136 ± 33 g, P < 0.001), but not in the placebo group (152 ± 32 versus 148 ± 38 g, P = 0.45).. Despite similar BP-lowering, only patients with TRH who were allocated to eplerenone experienced a reduction of LVM. Thus, our data suggest that in patients with TRH, mineralocorticoid receptor antagonists should be used preferentially in order to achieve an effective reduction of LVM along with the improvement of BP control.

Topics: Aged; Antihypertensive Agents; Blood Pressure; Coronary Vasospasm; Double-Blind Method; Drug Therapy, Combination; Eplerenone; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Magnetic Resonance Imaging; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Spironolactone

The aim of the study is to determine whether the selective aldosterone-receptor antagonist eplerenone delays onset of left ventricular (LV) systolic dysfunction or reduces LV hypertrophy in asymptomatic patients with moderate to severe aortic stenosis. Effects of eplerenone on LV diastolic function and progression of valve stenosis were also evaluated.. Sixty-five asymptomatic patients with a peak aortic valve velocity >3.0 m/s and normal LV function were randomized double blind to eplerenone, 100 mg daily (n = 33), or placebo (n = 32) for a median of 19 (interquartile range 15 to 25) months. Cardiac magnetic resonance imaging and echocardiography were performed and N-terminal pro-brain natriuretic peptide was measured at baseline and follow-up.. Symptomatic deterioration occurred in 13 subjects randomized to eplerenone and 11 to placebo (P = .34). Change in LV mass index (mean change +/- SD -0.3 +/- 14.6 vs +5.1 +/- 15 g/m(2) per year, P = .3), LV ejection fraction (+0.0% +/- 5.7% vs +0.8% +/- 5.7% per year, P = .9), and LV end-systolic volume index (-1.2 +/- 9 vs +0.04 +/- 12 mL/m(2) per year, P = .8) were small and similar for patients randomized to eplerenone and placebo, respectively. Decrease of aortic valve area (-0.11 +/- 0.22 vs -0.18 +/- 0.24 cm(2)/y, P = .2), worsening of LV diastolic dysfunction by echo-Doppler (E/E' +0.49 +/- 0.7 vs +1.32 +/- 2.0/year, P = .4), increase in the plasma level of N-terminal pro-brain natriuretic peptide (+63% vs +12% per year, P = .1), and decline in physical function score (9 +/- 34 vs 12 +/- 37/year, P = .7) were similar for subjects randomized to eplerenone and placebo, respectively.. In asymptomatic patients with moderate-severe aortic stenosis, eplerenone did not slow onset of LV systolic or diastolic dysfunction, decrease LV mass, or reduce progression of valve stenosis.

Topics: Aged; Aortic Valve Stenosis; Blood Flow Velocity; Echocardiography, Doppler; Eplerenone; Female; Humans; Hypertrophy, Left Ventricular; Magnetic Resonance Imaging; Male; Mineralocorticoid Receptor Antagonists; Spironolactone; Statistics, Nonparametric; Ventricular Dysfunction, Left

Elevated renin-angiotensin-aldosterone system activity correlates with left ventricular hypertrophy (LVH) and cardiovascular risk, but the relative contributions of angiotensin II and aldosterone remain unclear. This study compared LVH regression during treatment with the selective aldosterone blocker eplerenone, enalapril, and their combination in patients with hypertension.. A 9-month, double-blind, randomized study was performed in 202 patients with LVH and hypertension who received eplerenone 200 mg daily, enalapril 40 mg daily, or eplerenone 200 mg and enalapril 10 mg daily. At week 8, hydrochlorothiazide 12.5 to 25 mg and/or amlodipine 10 mg was added if diastolic blood pressure was >90 mm Hg. Change in left ventricular (LV) mass as assessed by MRI was the primary end point. Change in blood pressure, renin-angiotensin-aldosterone system hormones, albuminuria, and safety were also assessed. Eplerenone significantly reduced LV mass from baseline (-14.5+/-3.36 g; n=50) similarly to enalapril (-19.7+/-3.20 g; n=54; P=0.258), but eplerenone/enalapril (-27.2+/-3.39 g; n=49) was more effective than eplerenone alone (P=0.007). All treatments reduced systolic blood pressure and diastolic blood pressure from baseline (eplerenone, -23.8 and -11.9 mm Hg; enalapril, -24.7 and -13.4 mm Hg; and eplerenone/enalapril, -28.7 and -14.4 mm Hg, P=0.048, in systolic blood pressure compared with eplerenone alone). Cough was more common with enalapril than with eplerenone (P=0.033), and elevated potassium was more common with eplerenone.. Eplerenone was as effective as enalapril in LVH regression and blood pressure control. The combination of eplerenone and enalapril was more effective in reducing LV mass and systolic blood pressure than eplerenone alone.

Topics: Adult; Aged; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Double-Blind Method; Drug Synergism; Drug Therapy, Combination; Enalapril; Eplerenone; Female; Humans; Hydrochlorothiazide; Hypertension; Hypertrophy, Left Ventricular; Magnetic Resonance Imaging; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Myocardium; Potassium; Renin-Angiotensin System; Spironolactone; Treatment Outcome

Topics: Adenosine; Angioplasty, Balloon, Coronary; Anti-Arrhythmia Agents; Antihypertensive Agents; Atherectomy, Coronary; Atrial Fibrillation; Azithromycin; Chlamydophila Infections; Coronary Disease; Defibrillators, Implantable; Double-Blind Method; Eplerenone; Heart Failure; Heart Transplantation; Heart-Assist Devices; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertrophy, Left Ventricular; Myocardial Reperfusion; Pyridines; Radiology, Interventional; Spironolactone; Stents; Thiazepines; Thrombolytic Therapy

Mineralocorticoid receptor(MR) antagonism reduces sudden cardiac death in heart failure, but the underlying mechanism remains poorly understood. Concurrent treatment with an MR antagonist during rapid ventricular pacing (RVP) prevents development of adverse ventricular electrophysiological remodeling, interstitial fibrosis, inflammatory cytokine gene activation, and ventricular tachyarrhythmia inducibility without diminishing the extent of systolic dysfunction. We hypothesized that attenuating preexistent inflammatory pathways and myocardial fibrosis with eplerenone after systolic heart failure is established by rapid pacing can reduce electrical activation delays and arrhythmia vulnerability.. Dogs subjected to RVP for 8 weeks in the absence or presence of eplerenone treatment during the final 4 weeks of pacing were assessed by echocardiography, electrophysiology study,ventricular fibrosis measurements, and inflammatory cytokine mRNA expression analysis. Eplerenone reversed preexistent ventricular activation delays, interstitial fibrosis, inflammatory cytokine (interleukin-6, tumor necrosis factor-α) gene overexpression, and arrhythmia vulnerability in ventricular paced dogs with heart failure. Eplerenone failed to improve left ventricular systolic dysfunction or chamber enlargement. A correlation between severity of fibrosis and ventricular arrhythmia inducibility was found.. MR antagonism regresses rapid pacing-induced electrical delays, inflammatory cytokine gene activation, and fibrosis in heart failure. Ventricular arrhythmia vulnerability in heart failure is correlated with extent of fibrosis and electrical activation delays during premature excitation.

Topics: Action Potentials; Animals; Anti-Inflammatory Agents; Arrhythmias, Cardiac; Cardiac Pacing, Artificial; Cardiovascular Agents; Disease Models, Animal; Dogs; Eplerenone; Fibrosis; Heart Failure; Hypertrophy, Left Ventricular; Inflammation Mediators; Interleukin-6; Male; Mineralocorticoid Receptor Antagonists; Myocardium; Spironolactone; Time Factors; Tumor Necrosis Factor-alpha; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Remodeling

The addition of an aldosterone receptor antagonist on top of current optimal therapy (based on angiotensin II inhibition) has demonstrated an important clinical benefit in heart failure patients with systolic dysfunction. Whether this finding also applies to heart failure patients with preserved systolic function is unknown. Therefore, we have studied the effect of adding eplerenone to standard pharmacological heart failure therapy (angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and diuretic and β-blocker) in the progression of heart failure in spontaneously hypertensive heart failure (SHHF) rats.. Two-month-old SHHF rats were randomized to receive no treatment (SHHF group), a standard heart failure therapy (quinapril-torasemide-carvedilol; ST-SHHF group), or the combination of eplerenone and standard heart failure therapy (Eple+ST-SHHF group) for 20 months. Untreated SHHF was characterized by progressive left ventricular hypertrophy, fibrosis, and myocardial contractile and relaxation abnormalities, leading to pulmonary congestion. Despite similar blood pressure control, the addition of eplerenone to standard heart failure therapy further prevented left ventricular hypertrophy, contractile and relaxation alterations, and pulmonary congestion than standard heart failure therapy alone. ST-SHHF and Eple + ST-SHHF rats showed similar inhibition of structural extracellular matrix proteins collagen I, collagen III and fibronectin and metalloproteinase (MMP)-2, MMP-7, MMP-12, and MMP-13. However, only the coadministration of eplerenone with standard heart failure therapy normalized the expression of matricellular proteins thrombospondin 1, tenascin C, periostin, and secreted protein acidic rich in cysteine/osteonectin to values comparable to normotensive rats.. In a hypertensive heart failure rat model, the addition of eplerenone to conventional heart failure therapy further improves cardiac structural and functional parameters, delaying the progression of heart failure. These beneficial effects of eplerenone were associated with normalization of matricellular protein expression.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Drug Therapy, Combination; Eplerenone; Heart; Heart Failure; Hypertension; Hypertrophy, Left Ventricular; Male; Matrix Metalloproteinases; Mineralocorticoid Receptor Antagonists; Myocardium; Random Allocation; Rats; Rats, Inbred SHR; Spironolactone

Although aldosterone, acting via mineralocorticoid receptors, causes left ventricular (LV) hypertrophy in experimental models of high-aldosterone hypertension, little is known about the role of aldosterone or mineralocorticoid receptors in mediating adverse remodeling in response to chronic pressure overload.. We used the mineralocorticoid receptor-selective antagonist eplerenone (EPL) to test the role of mineralocorticoid receptors in mediating the transition from hypertrophy to failure in mice with chronic pressure overload caused by ascending aortic constriction (AAC). One week after AAC, mice were randomized to regular chow or chow containing EPL (200 mg/kg per day) for an additional 7 weeks. EPL had no significant effect on systolic blood pressure after AAC. Eight weeks after AAC, EPL treatment improved survival (94% versus 65%), attenuated the increases in LV end-diastolic (3.4+/-0.1 versus 3.7+/-0.1 mm) and end-systolic (2.0+/-0.1 versus 2.5+/-0.2 mm) dimensions, and ameliorated the decrease in fractional shortening (42+/-2% versus 34+/-4%). EPL also decreased myocardial fibrosis, myocyte apoptosis, and the ratio of matrix metalloproteinase-2/tissue inhibitor of matrix metalloproteinase-2. These beneficial effects of EPL were associated with less myocardial oxidative stress, as assessed by 3-nitrotyrosine staining, reduced expression of the adhesion molecule intercellular adhesion molecule-1, and reduced infiltration by macrophages.. Mineralocorticoid receptors play an important role in mediating the transition from LV hypertrophy to failure with chronic pressure overload. The effects of mineralocorticoid receptor stimulation are associated with alterations in the interstitial matrix and myocyte apoptosis and may be mediated, at least in part, by oxidative stress and inflammation.

Topics: Animals; Aorta; Apoptosis; Blood Pressure; Cell Size; Chronic Disease; Constriction, Pathologic; Drug Evaluation, Preclinical; Eplerenone; Fibrosis; Heart Failure; Hypertrophy, Left Ventricular; Intercellular Adhesion Molecule-1; Ligation; Male; Matrix Metalloproteinases; Mice; Mineralocorticoid Receptor Antagonists; Myocarditis; Myocardium; Myocytes, Cardiac; Oxidative Stress; Pressure; Random Allocation; Receptors, Mineralocorticoid; Spironolactone; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-2; Tyrosine

Osteopontin (OPN) is upregulated in several experimental models of cardiac fibrosis and remodeling. However, its direct effects remain unclear. We examined the hypothesis that OPN is important for the development of cardiac fibrosis and remodeling. Moreover, we examined whether the inhibitory effect of eplerenone (Ep), a novel aldosterone receptor antagonist, was mediated through the inhibition of OPN expression against cardiac fibrosis and remodeling. Wild-type (WT) and OPN-deficient mice were treated with angiotensin II (Ang II) for 4 weeks. WT mice receiving Ang II were divided into 2 groups: a control group and an Ep treatment group. Ang II treatment significantly elevated blood pressure and caused cardiac hypertrophy and fibrosis in WT mice. Ep treatment and OPN deficiency could reduce the Ang II-induced elevation of blood pressure and ameliorate the development of cardiac fibrosis, whereas Ep-only treatment abolished the development of cardiac hypertrophy. Most compelling, the reduction of cardiac fibrosis led to an impairment of cardiac systolic function and subsequent left ventricular dilatation in Ang II-treated OPN-deficient mice. These results suggest that OPN has a pivotal role in the development of Ang II-induced cardiac fibrosis and remodeling. Moreover, the effect of Ep on the prevention of cardiac fibrosis, but not cardiac hypertrophy, might be partially mediated through the inhibition of OPN expression.

Topics: Aldosterone; Angiotensin II; Animals; Apoptosis; Blood Pressure; Cardiomegaly; Cell Size; Eplerenone; Fibrosis; Heart Rate; Hypertrophy, Left Ventricular; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocardium; Myocytes, Cardiac; Osteopontin; Reverse Transcriptase Polymerase Chain Reaction; Sialoglycoproteins; Spironolactone; Ultrasonography; Ventricular Remodeling

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Animals; Class Ib Phosphatidylinositol 3-Kinase; Cognition Disorders; Contraindications; Drug Therapy, Combination; Enalapril; Eplerenone; Fibrinolytic Agents; Heart Failure; Humans; Hypertension; Hypertrophy, Left Ventricular; Isoenzymes; Mice; Mice, Knockout; Middle Aged; Mineralocorticoid Receptor Antagonists; Myocardial Infarction; Myocardial Reperfusion; Phosphatidylinositol 3-Kinases; Phosphoinositide-3 Kinase Inhibitors; Receptors, Adrenergic, beta; Spironolactone

Despite major advances many cardiovascular disorders remain poorly controlled. As a result the search for newer agents goes on. Anti-neurohormonal agents have been the most successful agents: beta-blockers, ACE inhibitors and angiotensin receptor blockers. To these we now add anti-aldosterone strategies with the phenomenal success of spironolactone in reducing mortality in severe heart failure. A more recent and more selective aldosterone receptor antagonist has been developed, eplerenone, and it shows considerable promise in managing and preventing the complications of hypertension. It may have a role both being anti-fibrotic and anti-neurohormonal in mild to moderate heart failure, in post-MI left ventricular dysfunction and in progressive renal disease. The EPHESUS trial which randomised patients with heart failure due to impaired left ventricular systolic function aims to randomise 6,200 patients to eplerenone or placebo on top of standard therapy and follow subjects until 1,012 deaths have occurred (approx. 2.5 years of follow up). This and other trials with the novel strategy of selective aldosterone antagonism are eagerly awaited. The beneficial effects established by the earliest anti-neurohormonal agents give us confidence that further benefits could be obtained by this intellectual strategy.

Topics: Eplerenone; Heart Failure; Humans; Hypertrophy, Left Ventricular; Mineralocorticoid Receptor Antagonists; Spironolactone