Efficacy of eplerenone added to renin-angiotensin blockade in hypertensive patients.
The efficacy and tolerability of eplerenone, a selective aldosterone blocker, was assessed when added to existing antihypertensive therapy with an ACE inhibitor or an angiotensin II receptor blocker (ARB). Hypertensive patients (n=341) whose blood pressure (BP) was not controlled despite ACE inhibitor or ARB were randomized (double-blind) to receive 50 mg eplerenone (increasing to 100 mg if required) once daily or placebo for 8 weeks. Diastolic and systolic BP and adverse events were recorded. By study end (week 8), mean seated diastolic BP was significantly reduced from week 0 among patients receiving eplerenone/ARB (-12.7+/-0.81 mm Hg) compared with those receiving placebo/ARB (-9.3+/-0.83 mm Hg). The change in mean seated diastolic BP was -9.9+/-0.88 mm Hg in eplerenone/ACE inhibitor patients and -8.0+/-0.86 mm Hg in placebo/ACE inhibitor patients (P=NS). Systolic BP levels were also significantly lower at week 8 for eplerenone/ACE inhibitor (-13.4+/-1.35 mm Hg) and eplerenone/ARB (-16.0+/-1.37 mm Hg) patients, respectively, compared with placebo/ACE inhibitor (-7.5+/-1.31 mm Hg) and placebo/ARB patients (-9.2+/-1.41 mm Hg). Adverse events were generally nonsevere and not significantly different between eplerenone and placebo. This study demonstrated that in patients whose BP was not controlled with an ACE inhibitor or ARB, the addition of eplerenone over an 8-week period significantly lowered systolic BP in both groups and diastolic BP in ARB patients. Selective aldosterone blockade with eplerenone, therefore, may be useful add-on therapy in hypertensive patients inadequately controlled on ACE inhibitor or ARB alone.
Krum
Henry
H
Clinical Pharmacology Unit, Monash University, Alfred Hospital, Prahran, Victoria , Australia. henry.krum@med.monash.edu.au
Nolly
Hector
H
Workman
Diane
D
He
Weizhong
W
Roniker
Barbara
B
Krause
Scott
S
Fakouhi
Kaffa
K
D015746:Abdominal Pain / Q000139:chemically induced; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001562:Benzimidazoles / Q000627:therapeutic use; D001565:Benzoates / Q000627:therapeutic use; D001713:Biphenyl Compounds / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D003967:Diarrhea / Q000139:chemically induced; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D000077545:Eplerenone; D005260:Female; D006261:Headache / Q000139:chemically induced; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D000077405:Irbesartan; D019808:Losartan / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010352:Patient Dropouts; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000077333:Telmisartan; D013777:Tetrazoles / Q000627:therapeutic use; D016896:Treatment Outcome; D014633:Valine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000068756:Valsartan
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001565:Benzoates; D001713:Biphenyl Compounds; D013777:Tetrazoles; D013148:Spironolactone; D000077545:Eplerenone; D000068756:Valsartan; D014633:Valine; D000077405:Irbesartan; D019808:Losartan; C081643:candesartan; D000077333:Telmisartan