The Use of Aldosterone Receptor Blockers in the Treatment

Dose-Response Trials in Essential Hypertension

In a multicenter, 8-week trial in 417 essential hypertensive patients eplerenone 50, 100, or 400 mg o.d. or 25, 50 or 200 mg b.i.d. was compared with spironolactone 50 mg b.i.d. or placebo.[11] All doses of eplerenone, whether given once or twice daily, produced reductions in both systolic and diastolic pressures that were significantly (p <0.05) greater than with placebo. The eplerenone-induced reduction in BP was dose-dependent; response to 100 mg of eplerenone was about 75% of that observed with 100 mg of spironolactone. The rate of adverse events reported with eplerenone was similar to that of placebo. A dose-dependent rise in plasma renin activity was noted in patients treated with eplerenone that was less in the patients treated with <400 mg of eplerenone than seen with 100 mg of spironolactone. Similar increases in plasma aldosterone concentrations were also observed in the active treatment groups compared with those receiving placebo. Small increases in mean serum potassium levels were seen in most of the active treatment groups. At least one serum potassium measurement that exceeded 5.5 mmol/L was seen in 17 patients equally distributed among all treatment groups, including placebo. No symptoms that could be related to the increased potassium values were reported, nor did this finding require drug discontinuation for any subject.

In this 8-week active drug treatment study, the only sex-hormone-related side effect, intermenstrual bleeding, was reported in one patient in the spironolactone treatment group. Specifically, no reports of impotence or gynecomastia were reported in any of the participants in the study.[11] It should be emphasized that the duration of active treatment (8 weeks) may not have been sufficiently long to exclude the possibility of this sex-hormone-related side effect with eplerenone. This study provided evidence of a dose-dependent antihypertensive efficacy of eplerenone but also to a single dose of spironolactone in comparison to placebo.

In another study employing 24-hour ambulatory BP monitoring eplerenone (25, 50, 100, or 200 mg) was compared with placebo.[12] All doses of eplerenone were significantly more effective in reducing BP than placebo. In this study one subject receiving placebo and one subject in the 200-mg/d eplerenone group had a serum potassium level >5.5 mmol/L. There were no dose-dependent increases in mean serum potassium in the eplerenone-treated groups while significant (p <0.01) dose-dependent increases in plasma renin and aldosterone were observed.[12] The frequency of side effects reported with eplerenone was not significantly greater than those reported for placebo in this study[12]; no sex-hormone-related side effects were reported.[11]

Previous PageSection 2 of 7J Clin Hypertens 6(11):632-635, 2004. © 2004 Le Jacq Communications, Inc.
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