Antihypertensive effect of the mineralocorticoid receptor antagonist eplerenone: a pooled analysis of patient-level data from comparative trials using regulatory-approved doses
Received 7 April 2018
Accepted for publication 24 June 2018
Published 20 September 2018 Volume 2018:14 Pages 233—246
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr Naga Venkata Amarnath Kommuri
Mireille Fernet,1 Bruce Beckerman,2 Paula Abreu,2 Katharina Lins,3 John Vincent,2 Ellen Burgess4
1Department of Medical Affairs, Pfizer Canada Inc., Kirkland, QC, Canada; 2Department of Clinical Affairs, Pfizer Inc., New York, NY, USA; 3Department of Medical Affairs, Pfizer Ltd., Tadworth, UK; 4Department of Medicine, Faculty of Medicine, University of Calgary, Calgary, AB, Canada
Purpose: Several 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.
Methods: Seventeen 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.
Results: A 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.
Conclusion: This 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.
Keywords: hypertension, eplerenone, aldosterone, cardiovascular, selective mineralocorticoid blocker
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF] View Full Text [HTML][Machine readable]