title: The velocity of antihypertensive effect of losartan/hydrochlorothiazide and angiotensin II receptor blocker.
abstract: 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.
authors.affiliation: Environment and Genome Research Center, Tohoku University Graduate School of Medicine and Pharmaceutical Sciences, Sendai, Japan. hmetoki@med.tohoku.ac.jp
authors.forename: Hirohito
authors.initials: H
authors.lastname: Metoki
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Ohkubo
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kikuya
authors.forename: Kei
authors.initials: K
authors.lastname: Asayama
authors.forename: Ryusuke
authors.initials: R
authors.lastname: Inoue
authors.forename: Taku
authors.initials: T
authors.lastname: Obara
authors.forename: Takuo
authors.initials: T
authors.lastname: Hirose
authors.forename: Michihiro
authors.initials: M
authors.lastname: Sato
authors.forename: Takanao
authors.initials: T
authors.lastname: Hashimoto
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Imai
mesh_terms: D000368:Aged; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure; D004338:Drug Combinations; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D019808:Losartan / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged
chemical_list: D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D004338:Drug Combinations; D006852:Hydrochlorothiazide; D019808:Losartan