Additive effect of drospirenone/17-beta-estradiol in hypertensive postmenopausal women receiving enalapril.
BACKGROUND
Aldosterone has been implicated in the pathogenesis of progressive cardiovascular disease. Drospirenone (DRSP) is a novel progestin with aldosterone receptor antagonist activity developed for hormone replacement therapy (HRT) as DRSP/17beta-estradiol (DRSP/ E2). We investigated the additive effect of DRSP/E2 versus placebo on 24-h ambulatory blood pressure (BP) in postmenopausal women with hypertension treated with enalapril maleate (ENA).


METHODS
This was a double-blind, randomized, two-parallel group trial. Twenty-four nonsmoking postmenopausal women receiving 10 mg of ENA twice a day before study were randomized to DRSP/E2 + ENA (n = 12) or placebo (P) + ENA (n = 12) for 14 days. Twenty-four-hour ambulatory BP, plasma renin activity, and serum aldosterone were determined at baseline and on day 14.


RESULTS
Compared to placebo, 24-h mean [SD] BP in the DRSP/E2 + ENA group decreased significantly from baseline (139/80 mm Hg), systolic (-9 [51 mm Hg, P = .014) and diastolic (-5 [4] mm Hg, P = .007). Essentially no change from baseline (139/83 mm Hg) in systolic or diastolic 24-h ambulatory BP were observed in the P + ENA group. Aldosterone (mean [SD]) increased from baseline by 2.6 [4.5] ng/dL in the DRSP/E2 + ENA group, and decreased by 0.3 [5.5] ng/dL in the P + ENA group (P = .08) consistent with an antimineralocorticoid effect.


CONCLUSIONS
Our results suggest a significant additive BP-lowering effect of DRSP/E2 on both systolic and diastolic BP in hypertensive postmenopausal women receiving ENA, consistent with an antimineralocorticoid effect. DRSP/E2, a HRT with antimineralocorticoid effects, could offer a novel potential mechanism for reducing cardiovascular end points in postmenopausal women.
Preston
Richard A
RA
Division of Clinical Pharmacology Clinical Research Center, University of Miami School of Medicine, Florida 33136, USA. rpreston@med.miami.edu
Alonso
Alberto
A
Panzitta
Darlene
D
Zhang
Paul
P
Karara
Adel H
AH
D000450:Aldosterone / Q000097:blood; D000736:Androstenes / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D018660:Blood Pressure Monitoring, Ambulatory; D004311:Double-Blind Method; D004338:Drug Combinations; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000627:therapeutic use*; D004958:Estradiol / Q000031:analogs & derivatives / Q000627:therapeutic use*; D015914:Estrogen Replacement Therapy; D005260:Female; D006339:Heart Rate; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D016896:Treatment Outcome
D000736:Androstenes; D000959:Antihypertensive Agents; D004338:Drug Combinations; D000451:Mineralocorticoid Receptor Antagonists; D000450:Aldosterone; D004958:Estradiol; D004656:Enalapril; C035144:drospirenone