A dose-response analysis of candesartan-hydrochlorothiazide combination therapy in patients with hypertension.
OBJECTIVE
To describe the antihypertensive dose-response of combination therapy with candesartan and hydrochlorothiazide (HCT).


METHODS
Data from 4632 men and women (sex ratio 1:1, mean age 54 years) with mild to moderate hypertension, who participated in one of seven randomized, double-blind, placebo-controlled studies with candesartan-HCT for 8-12 weeks, were entered in a common database. The daily dose of candesartan ranged from 2 to 32 mg, and that of HCT from 6.25 to 25mg. An E(max) model was used to describe the placebo-adjusted dose-response surface for systolic and diastolic blood pressure (BP) reductions.


RESULTS
The BP reduction increased with increasing doses of candesartan and HCT, ranging from 5.9 to 17.4 mmHg systolic, and from 2.8 to 10.2 mmHg diastolic with combination therapy. As these figures represent pure drug effects, the effect observed in placebo treated patients (mean reduction 6.0/5.6 mmHg) should be added to estimate the average BP reduction in the usual clinical setting. The reduction with candesartan-HCT represented fully additive contributions of the components.


CONCLUSIONS
The effect of candesartan-HCT is dose-related over a wide range of doses, and the effects of the components are fully additive. This analysis provides guidance for dosing.
Karlson
Björn Wilgot
BW
AstraZeneca R&D, Mölndal, Sweden. bjorn.w.karlson@astrazeneca.com
Zetterstrand
Sofia
S
Olofsson
Bertil
B
Elmfeldt
Dag
D
D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D001562:Benzimidazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D019411:Clinical Laboratory Techniques; D002985:Clinical Protocols; D003971:Diastole / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010361:Patients; D010919:Placebos / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D012106:Research; D013599:Systole / Q000187:drug effects; D013777:Tetrazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use
D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D010919:Placebos; D013777:Tetrazoles; D006852:Hydrochlorothiazide; C081643:candesartan