title: Antihypertensive effects of two fixed-dose combinations of losartan and hydrochlorothiazide versus hydrochlorothiazide monotherapy in subjects with ambulatory systolic hypertension.
abstract: BACKGROUND
  The efficacy of losartan (L) in combination with hydrochlorothiazide (HCTZ) has been demonstrated to reduce blood pressure. However, there are limited data on the effects of L/HCTZ combinations versus HCTZ monotherapies in reducing ambulatory systolic blood pressure. The aim of this study was to compare the effects of these treatment approaches in patients with ambulatory systolic hypertension.
  
  
  METHODS
  Patients were randomized to receive L 50 mg (n = 60) or HCTZ 12.5 mg (n = 60) for 6 weeks. Patients were then force-titrated to L 50/HCTZ 12.5 mg and to L 100/HCTZ 25 mg or were sham-titrated to HCTZ 12.5 mg and force-titrated to HCTZ 25 mg, respectively. Clinic and 24-h ambulatory blood pressure (ABP) were measured at baseline and after each 6-week treatment period.
  
  
  RESULTS
  We found that L 50 and HCTZ 12.5 induced significant and similar decreases in clinic and ABP. The combinations of L 50/HCTZ 12.5 and L 100/HCTZ 25 provided significantly greater decreases in clinic and ABP than did HCTZ monotherapies. The L 50/HCTZ 12.5 and L 100/HCTZ 25 combinations provided significant additional decreases in systolic/diastolic ABP during daytime (-5.3/-2.0 mm Hg; P <.001 and -5.8/-3.4 mm Hg; P <.001) and the other periods of the 24-h interval compared with the levels achieved by the previous treatment, indicating a clear dose-response relationship. However, increasing the dose of HCTZ from 12.5 mg to 25 mg was not associated with additional ABP reductions.
  
  
  CONCLUSIONS
  Combinations of L 50/HCTZ 12.5 and L 100/HCTZ 25 provided greater reductions in clinic and ABP than HCTZ monotherapies, with a clear dose-response relationship with regard to ABP. These results support the use of ABP monitoring when assessing the efficacy of antihypertensive therapies.
authors.affiliation: Hypertension Research Unit, Centre Hospitalier de l'Université Laval, Ste-Foy, Québec, Canada. Yves.Lacourciere@crchul.ulaval.ca
authors.forename: Yves
authors.initials: Y
authors.lastname: Lacourcière
authors.forename: Luc
authors.initials: L
authors.lastname: Poirier
mesh_terms: D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects*; D018660:Blood Pressure Monitoring, Ambulatory / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage*; D006973:Hypertension / Q000175:diagnosis / Q000188:drug therapy*; D019808:Losartan / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D010045:Outpatients; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D004338:Drug Combinations; D006852:Hydrochlorothiazide; D019808:Losartan