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Eplerenone Alone Or Combined With Enalapril Effectively Reduces Left Ventricular Hypertrophy

In patients with essential hypertension, eplerenone alone or in combination with an ACE inhibitor appears to be a promising therapy for reducing left ventricular hypertrophy (LVH), thus reducing morbidity and mortality.

Reversal of LVH is an important goal of antihypertensive therapy. Although elevated renin-angiotensin-aldosterone system activity has been shown to correlate with LVH and cardiovascular risk, the relative contributions of angiotensin II and aldosterone are unclear.

In a 9-month study of hypertensive patients with LVH, Bertram Pitt, MD, of the University of Michigan Medical School in Ann Arbor, Michigan, United States, and colleagues compared left ventricular (LV) mass reduction during treatment with the selective aldosterone blocker eplerenone, enalapril, and their combination.

A total of 202 LVH patients with a history of hypertension were randomised to receive eplerenone 200 mg daily, enalapril 40 mg daily, or eplerenone 200 mg and enalapril 10 mg daily after a 14 day run-in period on placebo.

In cases where BP failed to normalise (diastolic blood pressure [DBP] >90 mmHg or systolic blood pressure [SBP] >180 mmHg) by week 8, open-label hydrochlorothiazide (HCTZ) 12.5 to 25 mg, amlodipine 10 mg, or a combination was administered.

The primary study endpoint was assessment by magnetic resonance imaging of change in LV mass. Additionally, change in blood pressure, renin-angiotensin-aldosterone system hormones, albuminuria, and safety were evaluated.

Comparison of monotherapies showed that eplerenone and enalapril were similar in efficacy. Eplerenone significantly reduced LV mass from baseline (-14.5 ± 3.36 g; n=50), as did enalapril (-19.7 ± 3.20 g; n=54; P=0.258). Combination therapy with eplerenone/enalapril (-27.2 ± 3.39 g; n=49) was more effective than eplerenone alone (P=0.007).

Significant reductions from base line were observed for all treatment groups in mean SBP and DBP. Adverse reactions were reported with similar incidence between treatment groups.

The study was supported by a grant from Pharmacia Corp.
Circulation. 2003 Sep 29 [Epub ahead of print]. "Effects of Eplerenone, Enalapril, and Eplerenone/Enalapril in Patients With Essential Hypertension and Left Ventricular Hypertrophy. The 4E-Left Ventricular Hypertrophy Study"

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