Eplerenone for hypertension

Tam, Tina Sc; Wu, Meng; Masson, Sarah; Tsang, Matthew P; Stabler, Sarah; Kinkade, Angus; Tung, Anthony; Tejani, Aaron M

doi:10.1002/14651858.cd008996.pub2

Cited by 22 publications

(22 citation statements)

References 73 publications

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“…EPL had no significant effects on blood pressure levels. Our observation is consistent with the recent meta-analysis which shows EPL at a dose of 25 mg/day did not produce a statistically significant reduction in systolic or diastolic blood pressure 18 . Our data indicated that MRA maintain eGFR independently of its effects on blood pressure.…”

Section: Discussionsupporting

confidence: 93%

The effect of aldosterone and aldosterone blockade on the progression of chronic kidney disease: a randomized placebo-controlled clinical trial

Minakuchi

Wakino

Urai

et al. 2020

Sci Rep

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The progression of chronic kidney disease (CKD) cannot be completely inhibited. We first explored factors contributing to CKD progression in patients with CKD in a prospective observational study. In the next phase, we focused on the effects of aldosterone, conducting a single-blinded placebo-controlled study using the selective mineralocorticoid receptor antagonist (MRA), eplerenone (25 mg/day). We recruited patients with CKD stage 2 and 3 whose plasma aldosterone concentration was above 15 ng/dL based on the prior data of a prospective observational study. In the CKD cohort study (n = 141), baseline plasma aldosterone concentration was identified as an independent contributory factor for the future rate of change in estimated glomerular filtration rate (eGFR). When the cut-off value for aldosterone was set at 14.5 ng/dL, the decline rate was significantly higher in patients with higher plasma aldosterone concentration (− 1.22 ± 0.39 ml/min/1.73 m2/year vs. 0.39 ± 0.40 ml/min/1.73 m2/year, p = 0.0047). In the final intervention study, in the eplerenone group, eGFR dropped at 6 months after the initiation of the study, and thereafter eGFR was maintained until the end of the study. At 24 months and 36 months, eGFR was significantly higher in the eplerenone group than in the placebo group. In conclusion, MRA can be an effective strategy in preventing CKD progression, especially in patients with high plasma aldosterone.

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Section: Discussionsupporting

confidence: 93%

The effect of aldosterone and aldosterone blockade on the progression of chronic kidney disease: a randomized placebo-controlled clinical trial

Minakuchi

Wakino

Urai

et al. 2020

Sci Rep

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“…This is of major significance because hyperaldosteronism is associated with a plethora of cardiovascular comorbidities and is hallmarked by electrolyte dysregulation [ 9 ]. Moreover, drugs that target aldosterone and its mineralocorticoid receptor, such as spironolactone and eplerenone, are increasingly being used in the management of various pathologies, including hypertension, heart failure, arrhythmias and renal disease [ 10 , 11 ]. Therefore, it is critically important that the ion regulatory pathways of aldosterone are fully understood to understand the unintended consequences of aldosterone-related treatments.…”

Section: Introductionmentioning

confidence: 99%

Aldosterone, SGK1, and ion channels in the kidney

2018

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Hyperaldosteronism, a common cause of hypertension, is strongly connected to Na+, K+, and Mg2+ dysregulation. Owing to its steroidal structure, aldosterone is an active transcriptional modifier when bound to the mineralocorticoid receptor (MR) in cells expressing the enzyme 11β-hydroxysteroid dehydrogenase 2, such as those comprising the aldosterone-sensitive distal nephron (ASDN). One such up-regulated protein, the ubiquitous serum and glucocorticoid regulated kinase 1 (SGK1), has the capacity to modulate the surface expression and function of many classes of renal ion channels, including those that transport Na+ (ENaC), K+ (ROMK/BK), Ca2+ (TRPV4/5/6), Mg2+ (TRPM7/6), and Cl− (ClC-K, CFTR). Here, we discuss the mechanisms by which ASDN expressed channels are up-regulated by SGK1, while highlighting newly discovered pathways connecting aldosterone to nonselective cation channels that are permeable to Mg2+ (TRPM7) or Ca2+ (TRPV4).

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“…These results are similar to those seen in study-level pooled analyses including dosages of eplerenone from 50 to 400 mg daily. 27 , 28 Our descriptive secondary endpoint indicated that the percentage of patients controlled to the target BP of 140/90 was numerically greater with eplerenone than with placebo or active comparators. In the placebo-controlled studies, approximately 30% of patients were below target while on placebo, which is a common observation particularly in short-term studies.…”

Section: Discussionmentioning

confidence: 87%

Antihypertensive effect of the mineralocorticoid receptor antagonist eplerenone: a pooled analysis of patient-level data from comparative trials using regulatory-approved doses

Fernet

Beckerman²,

Abreu³

et al. 2018

VHRM

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PurposeSeveral options are available for the treatment of hypertension; however, many treated patients are still not below blood pressure (BP) target. Eplerenone, a selective mineralocorticoid receptor antagonist, is an approved treatment option for the management of patients with hypertension in a number of countries. This patient-level pooled analysis was conducted to document the efficacy and safety/tolerability of eplerenone at the dosages approved for use in hypertension in comparison to placebo or other approved antihypertensive agents.MethodsSeventeen Phase III studies conducted in patients with mild-to-moderate hypertension in the Eplerenone Hypertension Clinical Program were reviewed; eleven met the selection criteria. The primary endpoint was change from baseline in seated diastolic BP and seated systolic BP measured at the end of the study.ResultsA total of 2,698 patients were included in this per-protocol analysis. In patients treated for at least 6 weeks with a stable dose of eplerenone, doses of 50 mg daily and 100 mg daily were associated with greater reductions of seated systolic BP and seated diastolic BP compared with placebo (P<0.001) and active-controlled studies (P< 0.033). In the analysis of covariance model testing of the contribution of four factors (age, body mass index [BMI], history of cardiovascular disease, and diabetes) on the BP lowering effects of eplerenone, only BMI and age were associated with small though statistically significant changes in BP (<0.2 mmHg). Eplerenone was well tolerated; headache was the most common adverse event for patients in any group. Severe hyperkalemia (serum potassium level >6.0 mmol/L) occurred in up to 0.4% in the eplerenone groups, 0.4% in the placebo group, and 0.1% in the active-control group.ConclusionThis patient-level pooled analysis provides robust evidence that eplerenone, at 50 mg or 100 mg daily, was effective in lowering BP in patients with mild-to-moderate hypertension and was well tolerated.

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Eplerenone for hypertension

Abstract: Analysis 2.2. Comparison 2 Eplerenone direct dose comparisons, Outcome 2 Diastolic dose response..

Cited by 22 publications

References 73 publications

The effect of aldosterone and aldosterone blockade on the progression of chronic kidney disease: a randomized placebo-controlled clinical trial

The effect of aldosterone and aldosterone blockade on the progression of chronic kidney disease: a randomized placebo-controlled clinical trial

Aldosterone, SGK1, and ion channels in the kidney

Antihypertensive effect of the mineralocorticoid receptor antagonist eplerenone: a pooled analysis of patient-level data from comparative trials using regulatory-approved doses

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