Utility of semiautomatic clinic and 24-h ambulatory blood pressure measurements to evaluate combination therapy: the Ramipril-Hydrochlorothiazide Hypertension trial

J Hum Hypertens. 2008 Aug;22(8):559-68. doi: 10.1038/jhh.2008.26. Epub 2008 May 8.


Angiotensin-converting enzyme inhibitors combined with higher doses of hydrochlorothiazide (HCT), that is, 25 mg daily, have been recognized as an effective form of antihypertensive therapy. To evaluate the coadministration of 20 mg ramipril with 25 mg HCT, we carried out a randomized, double-blind, controlled trial with two dose schedules of ramipril (20 mg q.d. and 10 mg b.i.d.) and HCT monotherapy arms as comparators in 354 patients with stage 2 hypertension. The clinic blood pressure (BP) was assessed using a semiautomatic digital device and 24-h BP was measured using ambulatory BP recordings at baseline and after 8 weeks of therapy. At baseline, the demographics and baseline BP values were similar in the four treatment groups (age: 51-53 years, 52-58% male, 64-68% non-black, clinic BP: 155-158/103-104 mm Hg). Ramipril-HCT induced significantly greater reductions in both the clinic and ambulatory BP than the HCT and ramipril monotherapy treatments (for example, additional reductions in ambulatory BP on ramipril-HCT ranged from -7.3/-5.2 to -10.3/-7.4 mm Hg compared to the monotherapies, all P<0.001). Reductions from baseline were still numerically greater for the clinic BPs derived from device measurements than those for the BP values derived from 24-h ambulatory BP measurements (changes in clinic diastolic BP ranged from -8.5 to -15.5 mm Hg across treatment groups, whereas changes in ambulatory diastolic BP were -4.7 to -12.0 mm Hg for the same groups). Thus, these data support the use of ambulatory BP monitoring even when automated BP devices are used for the assessment of clinical BP in trials that attempt to differentiate BP responses among active comparator groups. In conclusion, based on its efficacy and tolerability profile the combination of ramipril and HCT was shown to be effective therapy for the treatment of stage 2 hypertension.

Trial registration: ClinicalTrials.gov NCT00355589.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Blood Pressure / drug effects*
  • Blood Pressure / physiology
  • Blood Pressure Determination / statistics & numerical data*
  • Diuretics / administration & dosage
  • Diuretics / therapeutic use*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Humans
  • Hydrochlorothiazide / administration & dosage
  • Hydrochlorothiazide / therapeutic use*
  • Hypertension / drug therapy
  • Hypertension / physiopathology*
  • Male
  • Middle Aged
  • Ramipril / administration & dosage
  • Ramipril / therapeutic use*
  • Treatment Outcome


  • Angiotensin-Converting Enzyme Inhibitors
  • Diuretics
  • Hydrochlorothiazide
  • Ramipril

Associated data

  • ClinicalTrials.gov/NCT00355589