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

Hirohito Metoki, Takayoshi Ohkubo, Masahiro Kikuya, Kei Asayama, Ryusuke Inoue, Taku Obara, Takuo Hirose, Michihiro Sato, Takanao Hashimoto, Yutaka Imai

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17 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1478-1486
Number of pages9
JournalJournal of Hypertension
Issue number7
Publication statusPublished - 2012 Jul


  • angiotensin II receptor blockers
  • exponential decay function
  • home blood pressure measurements
  • losartan/HCTZ combination
  • maximal effect
  • stabilization time


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