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 reviewers approved by Dr Cristina Weinberg
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
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