SciCombinator

Discover the most talked about and latest scientific content & concepts.

Concept: Eplerenone

139

Aldosterone antagonists slow the progression of chronic kidney disease (CKD), but their use is limited by hyperkalemia, especially when associated with RAS inhibitors. We examined the renoprotective effects of Ly, a novel non-steroidal mineralocorticoid receptor (MR) blocker, through two experimental protocols: In Protocol 1, male Munich-Wistar rats underwent 5/6 renal ablation (Nx), being divided into: Nx+V, receiving vehicle, Nx+Eple, given eplerenone, 150 mg/kg/day, and Nx+Ly, given Ly, 20 mg/kg/day. A group of untreated sham-operated rats was also studied. Ly markedly raised plasma renin activity (PRA) and aldosterone, and exerted more effective anti-albuminuric and renoprotective action than eplerenone. In Protocol 2, Nx rats remained untreated until Day 60, when they were divided into: Nx+V receiving vehicle; Nx+L treated with losartan, 50 mg/kg/day; Nx+L+Eple, given losartan and eplerenone, and Nx+L+Ly, given losartan and Ly. Treatments lasted for 90 days. As an add-on to losartan, Ly normalized blood pressure and albuminuria, and prevented CKD progression more effectively than eplerenone. This effect was associated with strong stimulation of PRA and aldosterone. Despite exhibiting higher affinity for the MR than either eplerenone or spironolactone, Ly caused no hyperkalemia. Ly may become a novel asset in the effort to detain the progression of CKD.

Concepts: Chronic kidney disease, Kidney, Nephrology, Blood pressure, Aldosterone, Spironolactone, Eplerenone, Renin

28

QUESTION In patients with left ventricular (LV) dysfunction, what is the relative efficacy of eplerenone and other aldosterone antagonists (AAs)? REVIEW SCOPE Included studies compared eplerenone or other AAs with control (placebo, angiotensin-converting enzyme inhibitor, angiotensin-receptor blocker, or β-blocker) in patients > 18 years of age with symptomatic or asymptomatic LV dysfunction, had ≥ 8 weeks of follow-up, and reported ≥ 1 outcome of interest. Studies comparing AAs with each other were excluded. Outcomes were all-cause mortality, cardiovascular (CV) mortality, gynecomastia {per trial definition in individual studies}*, and hyperkalemia {serum potassium > 5.5 mEq/L}*. REVIEW METHODS MEDLINE, EMBASE/Excerpta Medica, CINAHL, and Cochrane Central Register of Controlled Trials (all to Jul 2011); reference lists; and reviews were searched for randomized controlled trials (RCTs). 16 RCTs (n = 12 505, mean age 55 to 69 y, 54% to 87% men) met selection criteria. 4 RCTs included patients after acute myocardial infarction LV dysfunction, and 12 included patients with heart failure. Study drugs were spironolactone (10 RCTs), canrenone (3 RCTs), and eplerenone (3 RCTs). Risk for bias (Cochrane criteria) was low for 8 RCTs, intermediate for 7, and high for 1. MAIN RESULTS Eplerenone and other AAs reduced all-cause mortality and CV mortality compared with no AA (Table). Eplerenone increased risk for hyperkalemia, and other AAs increased risk for gynecomastia, compared with no AA (Table). Based on an indirect comparison, other AAs reduced mortality more than eplerenone (P = 0.009). CONCLUSION Based on an indirect comparison, eplerenone is not more effective at reducing mortality for adults with left ventricular dysfunction than other aldosterone antagonists.Eplerenone or other AAs vs control in patients with left ventricular dysfunction†OutcomesNumber of trials (n)Weighted event ratesAt 2 to 24 moEplerenoneControl‡RRR (95% CI)NNT (CI)All-cause mortality2 (9369)14%16%15% (7 to 23)41 (27 to 88)CV mortality2 (9369)12%14%17% (8 to 25)42 (29 to 88)Gynecomastia2 (9361)0.49%0.66%26% (-27 to 57)NSRRI (CI)NNH (CI)Hyperkalemia3 (9489)6.1%3.8%72% (19 to 147)37 (19 to 140)Other AA§Control‡RRR (95% CI)NNT (CI)All-cause mortality12 (3569)19%25%26% (17 to 34)16 (12 to 24)CV mortality4 (2553)26%34%25% (16 to 33)12 (9 to 19)RRI (CI)NNH (CI)Gynecomastia6 (2279)5.4%0.86%526% (238 to 1057)23 (11 to 49)Hyperkalemia10 (3342)8.1%4.5%80% (-17 to 291)NS†AA = aldosterone antagonist; CV = cardiovascular; NS = not significant; other abbreviations defined in Glossary. Weighted event rates, RRR, RRI, NNT, NNH, and CI calculated from control event rates and risk ratios in article using a random-effects model.‡Placebo, angiotensin-converting enzyme inhibitor, angiotensin-receptor blocker, or β-blocker.§Other AAs were spironolactone or canrenone.

Concepts: Myocardial infarction, Hypertension, Heart failure, Spironolactone, Aldosterone antagonist, Eplerenone, ACE inhibitor, Hyperkalemia

28

In the presence of salt, aldosterone causes hypertension and organ damage via the mineralocorticoid receptor (MR) through various mechanisms. MR antagonists are considered to be potassium-sparing diuretics that exert their effect by blocking MR in the kidney, and they are not the first choice for treating hypertension. However, the importance and usefulness of inhibiting aldosterone in the management of hypertension have recently been revealed in both the basic and clinical fields. In Japan, both the selective MR antagonist eplerenone and the non-selective MR antagonist spironolactone are indicated for the treatment of hypertension. Although these drugs are generally used in the same manner, in some cases they require differentiation. This differentiation is divided into two types due to the differences in their features and differences in their contraindications in Japan. Based on a number of studies on MR antagonists that have been recently published, the diseases and clinical conditions targeted by MR antagonists appear to be likely to increase in the future. In Japan, we consider it necessary to carefully differentiate spironolactone from eplerenone in regard to their intended uses.Hypertension Research advance online publication, 22 November 2012; doi:10.1038/hr.2012.182.

Concepts: Hypertension, Aldosterone, Receptor antagonist, Spironolactone, Potassium-sparing diuretic, Diuretic, Aldosterone antagonist, Eplerenone

25

The aldosterone inhibitor eplerenone (EPL) has been shown to reduce the incidence of atrial fibrillation (AF) in patients with systolic heart failure, but the mechanism is unknown.

Concepts: Cardiology, Heart failure, Heart, Atrial fibrillation, Aldosterone, Atrial flutter, Aldosterone antagonist, Eplerenone

23

Eplerenone (EPL), an antagonist of the mineralocorticoid receptor, is beneficial for atrial fibrillation and atrial fibrosis. However, the underlying mechanism remains less well known. We aimed to investigate the effect of EPL on atrial fibrosis using a mouse with selective atrial fibrosis and to explore the underlying mechanisms.

Concepts: Signal transduction, Atrial fibrillation, Receptor, Nuclear receptor, Eplerenone, Mineralocorticoid, Mineralocorticoid receptor

22

AZD9977 is the first MR modulator in clinical development exerting similar organ protection as eplerenone with minimal urinary electrolyte effects in pre-clinical studies. The aim was to perform the initial clinical assessment of AZD9977.

Concepts: Pharmacology, Kidney, Pre-clinical development, Clinical psychology, Eplerenone, Mineralocorticoid, Mineralocorticoid receptor

2

While aldosterone antagonists have proven benefit among post-myocardial infarction (MI) patients with low ejection fraction (EF), how this treatment is used among older MI patients in routine practice is not well described.

Concepts: Myocardial infarction, Atherosclerosis, Cardiology, Heart failure, Ejection fraction, Aldosterone, Aldosterone antagonist, Eplerenone

0

Long-lasting postoperative macular edema is a therapeutic challenge. The authors report an efficient combination therapy of oral mineralocorticoid receptor antagonists (eplerenone [Inspra; Pfizer, New York City, NY] or spironolactone, 25 mg/day to 50 mg/day) and topical dexamethasone (four times/day and progressive dose tapering) in three refractory cases following complex cataract or retinal detachment surgery. In Case 1, central macular thickness (CMT) decreased from 523 μm to 214 μm and visual acuity (VA) improved from 20/200 to 20/50 during a 6-month period. In Cases 2 and 3, CMT improved from 505 μm to 333 μm and from 438 μm to 316 μm during 5- and 3-month periods, respectively; however, VA remained unchanged (20/100 and 20/200) due to photoreceptor damage. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:936-942.].

Concepts: Receptor, Retina, Receptor antagonist, Ophthalmology, Pfizer, Eplerenone, New York City, Mineralocorticoid receptor

0

Mineralocorticoid receptor antagonists (MRAs) are best known as potassium-sparing diuretics due to their blockade of aldosterone action in renal epithelial tissues. They are also beneficial for the treatment of heart failure, primarily due to effects in non-epithelial tissues. Currently there are only two steroidal MRAs that have been approved for use; spironolactone (and its active metabolite canrenone) and eplerenone. However, the search is on for novel generations of MRAs with increased potency and tissue selectivity. A number of novel non-steroidal compounds are in preclinical and early development, with one agent moving to phase III trials. The development of these agents and the mechanisms for their pharmacologic superiority compared to earlier generations of MRAs will be discussed in this review.

Concepts: Pharmacology, Hypertension, Aldosterone, Spironolactone, Potassium-sparing diuretic, Diuretic, Aldosterone antagonist, Eplerenone

0

This study aimed to evaluate the specific role of the 2 available mineralocorticoid receptor antagonists (MRAs), eplerenone and spironolactone, on the modulation of galectin-3 (Gal-3) and interleukin (IL)-33/ST2 signaling in an experimental model of left ventricular systolic dysfunction after acute myocardial infarction (MI).

Concepts: Myocardial infarction, Atherosclerosis, Hypertension, Receptor antagonist, Troponin, Eplerenone, Ventricular fibrillation, Mineralocorticoid receptor