Gender influence on the dose-ranging of a low-dose perindopril-indapamide combination in hypertension: effect on systolic and pulse pressure.
BACKGROUND
Dose-ranging of antihypertensive agents have been done to optimize diastolic blood pressure (DBP) reduction, but with little information on systolic (SBP), mean (MBP), or pulse (PP) pressures. A low-dose combination of perindopril (Per) and indapamide (Ind) has been shown to reduce more SBP than atenolol for the same DBP reduction. However, the possible influence of gender on this finding has never been tested.


OBJECTIVE
A database of five randomized, double-blind, dose-ranging studies was established to determine the optimal dose of the Per/Ind combination in hypertensive men and women. A total of 2907 patients were treated by either placebo or various combinations associating Per (2, 4, 8 mg) and Ind (0.625, 1.25, 2.5 mg).


RESULTS
In the overall population, there was a significant dose-response relationship (P < 0.001) for doubling the dose of Per 2/Ind 0.625 mg up to Per 8/Ind 2.5 mg with a progressive fall in SBP, DBP, MBP. When men and women were analyzed by dose, SBP, DBP and MBP (but not PP) decreased significantly more in women than in men until the Per 4/Ind 1.25 dosage was reached. Thereafter, with higher dosages, generating a slight but significant hypokalemia, the finding was reversed, resulting in a gender interaction in the overall population.


CONCLUSIONS
In hypertensive subjects, the low-dose combinations Per 2/Ind 0.625 and Per 4/Ind 1.25 are the most effective in reducing blood pressure and avoiding hypokalemia. This effect is more pronounced in women, in which increased SBP and PP are predominant hemodynamic features.
Safar
Michel E
ME
Medecine Interne 1, Hôpital Broussais, Paris, France. michel.safar@brs.ap-hop-paris
Myers
Martin G
MG
Leenen
Frans
F
Asmar
Roland
R
D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage; D000959:Antihypertensive Agents / Q000008:administration & dosage; D001794:Blood Pressure / Q000187:drug effects; D016208:Databases, Factual; D004232:Diuretics / Q000008:administration & dosage; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology*; D007190:Indapamide / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D020913:Perindopril / Q000008:administration & dosage*; D012727:Sex Characteristics
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D004232:Diuretics; D007190:Indapamide; D020913:Perindopril