Circulation. 2003;108:1831-1838
Published online before print September 29, 2003, doi: 10.1161/01.CIR.0000091405.00772.6E
Published online before print September 29, 2003, doi: 10.1161/01.CIR.0000091405.00772.6E
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(Circulation. 2003;108:1831.)
© 2003 American Heart Association, Inc.
Clinical Investigation and Reports |
Effects of Eplerenone, Enalapril, and Eplerenone/Enalapril in Patients With Essential Hypertension and Left Ventricular Hypertrophy
The 4E–Left Ventricular Hypertrophy Study
From the University of Michigan Health System (B.P.), Ann Arbor, Mich; St Francis Hospital (N.R.), Stony Brook University, Roslyn, NY; Franz-Volhard-Klinik (R.W.), Berlin, Germany; Centre d’Investigation Clinique (F.Z.), Hôpital Jeanne d’Arc, Dommartin-Les-Toul, France; Lenox Hill Hospital (R.A.P.), New York, NY; New York University School of Medicine (R.A.P.), New York, NY; Pharmacia Corporation (B.R., J.K., S.K., D.B.), Skokie, Ill; and Brigham and Women’s Hospital (G.H.W.), Harvard Medical School, Boston, Mass.
Correspondence to Bertram Pitt, MD, Professor of Internal Medicine, University of Michigan Medical School, 1500 E Medical Center Dr, Ann Arbor, MI 48109. E-mail bpitt{at}umich.edu
Received February 3, 2003; de novo received June 6, 2003; revision received July 23, 2003; accepted July 26, 2003.
Background— Elevated renin-angiotensin-aldosterone system activity correlates with left ventricular hypertrophy (LVH) and cardiovascular risk, but the relative contributions of angiotensin II and aldosterone remain unclear. This study compared LVH regression during treatment with the selective aldosterone blocker eplerenone, enalapril, and their combination in patients with hypertension.
Methods and Results— A 9-month, double-blind, randomized study was performed in 202 patients with LVH and hypertension who received eplerenone 200 mg daily, enalapril 40 mg daily, or eplerenone 200 mg and enalapril 10 mg daily. At week 8, hydrochlorothiazide 12.5 to 25 mg and/or amlodipine 10 mg was added if diastolic blood pressure was >90 mm Hg. Change in left ventricular (LV) mass as assessed by MRI was the primary end point. Change in blood pressure, renin-angiotensin-aldosterone system hormones, albuminuria, and safety were also assessed. Eplerenone significantly reduced LV mass from baseline (-14.5±3.36 g; n=50) similarly to enalapril (-19.7±3.20 g; n=54; P=0.258), but eplerenone/enalapril (-27.2±3.39 g; n=49) was more effective than eplerenone alone (P=0.007). All treatments reduced systolic blood pressure and diastolic blood pressure from baseline (eplerenone, -23.8 and -11.9 mm Hg; enalapril, -24.7 and -13.4 mm Hg; and eplerenone/enalapril, -28.7 and -14.4 mm Hg, P=0.048, in systolic blood pressure compared with eplerenone alone). Cough was more common with enalapril than with eplerenone (P=0.033), and elevated potassium was more common with eplerenone.
Conclusions— Eplerenone was as effective as enalapril in LVH regression and blood pressure control. The combination of eplerenone and enalapril was more effective in reducing LV mass and systolic blood pressure than eplerenone alone.
Key Words: hypertrophy • ventricles • blood pressure • hypertension
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