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The velocity of antihypertensive effect of losartan/hydrochlorothiazide and angiotensin II receptor blocker

Metoki, Hirohitoa,b; Ohkubo, Takayoshic,d; Kikuya, Masahiroc; Asayama, Keic; Inoue, Ryusukee; Obara, Takua; Hirose, Takuoc; Sato, Michihiroc; Hashimoto, Takanaoc; Imai, YutakacThe J-HOME-AI Study group

doi: 10.1097/HJH.0b013e328353f1fe
ORIGINAL PAPERS: Therapeutic aspects

Objective: The hypotensive effect and the time to attain the maximum antihypertensive effect (stabilization time) of losartan/hydrochlorothiazide (HCTZ) combination therapy and therapy with a maximal dose of angiotensin II receptor blockers (ARBs) in patients who failed to achieve adequate blood pressure (BP) control on a medium-dose of ARBs were compared by analyzing exponential decay functions using daily serial morning home BP measurements.

Methods: Essential hypertensive patients treated with a medium dose of ARB, in whom a target home SBP (135 mmHg) was not achieved, were randomized into two groups: a combination group (n = 110) and a maximal-dose ARB group (n = 111).

Results: The combination therapy provided additional reduction of 5.2 mmHg [95% confidence interval (CI) 1.8 to 8.5 mmHg, P = 0.003] in home SBP over the maximal-dose ARB therapy in 8 weeks after randomization. A greater reduction in the home SBP values was seen in the combination group than in the maximal-dose ARB group from the second day after randomization on the basis of a linear mixed model. The maximum antihypertensive effect and stabilization time for home SBP were 10.9 ± 5.0 mmHg and 7.3 ± 29.7 days, respectively, in the combination group, whereas the corresponding values in the maximal-dose ARB group were 7.9 ± 2.6 mmHg and 122.3 ± 42.7 days, respectively, on the basis of a nonlinear mixed model.

Conclusions: Changing from a medium dose of ARB monotherapy to combination therapy was more effective in the reduction of home SBP and achieved goal BP more rapidly than increasing the ARB dose. Home BP measurement is a useful tool for characterizing the antihypertensive effects of drugs.

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aEnvironment and Genome Research Center

bDepartment of Gynecology and Obsterics

cDepartment of Planning for Drug Development and Clinical Evaluation, Tohoku University Graduate School of Medicine and Pharmaceutical Sciences, Sendai

dDepartment of Health Science, Shiga University of Medical Science, Otsu

eMedical Information Technology Center, Tohoku University Hospital, Sendai, Japan

Correspondence to Hirohito Metoki, Environment and Genome Research Center, Tohoku University Graduate School of Medicine, Seiryo-cho 2–1, Aobaku, Sendai 980–8575, Japan. E-mail:

Abbreviations: ANCOVA, analysis of covariance; ARB, angiotensin II receptor antagonist; ARBs, angiotensin II receptor blockers; BP, blood pressure; HBP, home blood pressure; HCTZ, hydrochlorothiazide; RAS, renin–angiotensin system

Received 6 September, 2011

Revised 19 February, 2012

Accepted 21 March, 2012

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© 2012 Lippincott Williams & Wilkins, Inc.