title: Randomized trial comparing the velocities of the antihypertensive effects on home blood pressure of candesartan and candesartan with hydrochlorothiazide.
abstract: We aimed to evaluate the hypotensive effect and the time to attain the maximal antihypertensive effect (stabilization time) of 8 mg candesartan/6.25 mg hydrochlorothiazide (HCTZ) combination therapy (combination regimen) and therapy with an increased candesartan dose (12 mg; maximum dose regimen) using home blood pressure (BP) measurements. A prospective, multicenter, open-label, randomized, comparative trial was conducted. Essential hypertensive patients who failed to achieve adequate BP control (systolic BP (SBP) ⩽ 135 mm Hg) on 8 mg candesartan alone were randomized to two groups: the combination regimen (n=103) and the maximum dose regimen (n=103). Home morning SBP reduction at 8 weeks after randomization was 11.4 ± 1.3 mm Hg in the combination regimen and 7.8 ± 1 .2 mm Hg in the maximum dose regimen. The combination regimen provided additional reduction of 4.0 mm Hg (95% confidence interval (CI): 0.8-7.2 mm Hg, P=0.01) in home morning SBP over the maximum dose regimen at 8 weeks after randomization. The maximal antihypertensive effect and stabilization time for home SBP were 9.4 mm Hg and 37.1 days (P<0.0001), respectively, with the combination regimen. The maximum dose regimen decreased home SBP with a very gentle slope, and estimated maximal effect and estimated stabilization time were not significant (P>0.2). The rate of achieving target BP (home morning SBP <135 mm Hg) was significantly higher with the combination regimen than with the maximum dose regimen (52.4 vs. 30.1%, P=0.002). In conclusion, changing from 8 mg candesartan to combination therapy was more effective in reducing home SBP and achieving goal BP more rapidly than increasing the candesartan dose.
authors.affiliation: Department of Planning for Drug Development and Clinical Evaluation, Tohoku University Graduate School of Pharmaceutical Sciences, Sendai, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Hosaka
authors.affiliation: Department of Community Medical Supports, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.
authors.forename: Hirohito
authors.initials: H
authors.lastname: Metoki
authors.affiliation: Department of Pharmacy, Tohoku University Hospital, Sendai, Japan.
authors.forename: Michihiro
authors.initials: M
authors.lastname: Satoh
authors.affiliation: Department of Hygiene and Public Health, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Ohkubo
authors.affiliation: Department of Planning for Drug Development and Clinical Evaluation, Tohoku University Graduate School of Pharmaceutical Sciences, Sendai, Japan.|Department of Hygiene and Public Health, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Asayama
authors.affiliation: Department of Preventive Medicine and Epidemiology, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kikuya
authors.affiliation: Department of Medical Informatics, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Ryusuke
authors.initials: R
authors.lastname: Inoue
authors.affiliation: Department of Pharmacy, Tohoku University Hospital, Sendai, Japan.|Department of Preventive Medicine and Epidemiology, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Obara
authors.affiliation: Center for Interdisciplinary Research in Biology (CIRB), Collège de France, Paris, France.
authors.forename: Takuo
authors.initials: T
authors.lastname: Hirose
authors.affiliation: Department of Planning for Drug Development and Clinical Evaluation, Tohoku University Graduate School of Pharmaceutical Sciences, Sendai, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Imai
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D001794:Blood Pressure; D004232:Diuretics / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013777:Tetrazoles / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D004232:Diuretics; D013777:Tetrazoles; D006852:Hydrochlorothiazide; C081643:candesartan