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

• Published in: Journal of human hypertension Vol. 22; no. 8; pp. 559 - 568
• Main Authors: White, W B, Cleveland, J M, Rolleri, R L
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.08.2008; Nature Publishing; Nature Publishing Group
• Subjects: Angiotensin; Angiotensin-converting enzyme inhibitors; Angiotensin-Converting Enzyme Inhibitors - administration & dosage; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Antihypertensives; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Blood pressure; Blood Pressure - drug effects; Blood Pressure - physiology; Blood Pressure Determination - utilization; Cardiology. Vascular system; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Clinical trials; Demography; Diagnosis; Diuretics; Diuretics - administration & dosage; Diuretics - therapeutic use; Dosage and administration; Dose-Response Relationship, Drug; Double-Blind Method; Drug therapy; Drug Therapy, Combination; Epidemiology; Female; Follow-Up Studies; Health Administration; Humans; Hydrochlorothiazide; Hydrochlorothiazide - administration & dosage; Hydrochlorothiazide - therapeutic use; Hypertension; Hypertension - drug therapy; Hypertension - physiopathology; Male; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; original-article; Peptidyl-dipeptidase A; Public Health; Ramipril; Ramipril - administration & dosage; Ramipril - therapeutic use; Treatment Outcome; United States; ambulatory blood pressure monitoring; combination therapy; clinical trials; ACE inhibitor; ramipril; hydrochlorothiazide; Cardiovascular disease; Ramipril; Semiautomatic; Diuretic; Peptidyl-dipeptidase A; Arterial pressure; Blood pressure; Ambulatory; Monitoring; Hypertension; Drug combination; Enzyme; Enzyme inhibitor; Hydrochlorothiazide; Peptidases; Sulfonamides; Hydrolases; Peptidyl-dipeptidases; Antihypertensive agent; Combined treatment; Thiazide; Pressure measurement
• ISSN: 0950-9240; 1476-5527
• DOI: 10.1038/jhh.2008.26

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.