Effects of eplerenone, enalapril, and eplerenone/enalapril in patients with essential hypertension and left ventricular hypertrophy: the 4E-left ventricular hypertrophy study.
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.


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.
D000328:Adult; D000368:Aged; D017311:Amlodipine / Q000008:administration & dosage / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000008:administration & dosage / Q000627:therapeutic use*; D000077545:Eplerenone; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage / Q000627:therapeutic use; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy* / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D009206:Myocardium / Q000473:pathology; D011188:Potassium / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology; D013148:Spironolactone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D016896:Treatment Outcome
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D000451:Mineralocorticoid Receptor Antagonists; D006852:Hydrochlorothiazide; D017311:Amlodipine; D013148:Spironolactone; D000077545:Eplerenone; D004656:Enalapril; D011188:Potassium