title: Comparison of different fixed antihypertensive combination drugs: a double-blind, placebo-controlled parallel group study.
abstract: OBJECTIVE
  To compare the effects of fixed-dose preparations containing 180 mg sustained-release verapamil and 2 mg trandolapril, 100/25 mg atenolol/chlorthalidone, 20/12.5 mg lisinopril/hydrochlorothiazide and placebo in patients with essential hypertension.
  
  
  METHODS
  A 4-week placebo run-in period followed by a double-blind, placebo-controlled parallel group study lasting 8 weeks.
  
  
  METHODS
  Office practices (21 centres).
  
  
  METHODS
  Patients with essential hypertension (World Health Organization grades I or II); supine diastolic blood pressure 101-114 mmHg in week 4 of the run-in period; 215 patients were enrolled, of whom 205 were assigned randomly to double-blind therapy.
  
  
  METHODS
  Reduction in supine and standing blood pressures.
  
  
  RESULTS
  All three active treatments with a single daily dose were significantly more effective than was placebo in reducing the blood pressure of seated subjects (P=0.0001). The reductions in sitting diastolic blood pressure (DBP) from baseline to the last visit with each active treatment were comparable: 13 mmHg [95% confidence interval (CI) 16-9] with sustained-release verapamil/trandolapril, 13 mmHg (16-9) with atenolol/chlorthalidone and 12 mmHg (15-8) with lisinopril/hydrochlorothiazide. Normalization of blood pressure (DBP < 90 mmHg) was observed in 48% of patients with sustained-release verapamil/trandolapril, in 46% with atenolol/chlorthalidone and in 40% with lisinopril/hydrochlorothiazide. Response rates (normalization of DBP or a reduction in DBP by > 10 mmHg) with each active treatment were 72% for sustained-release verapamil/trandolapril, 76% for atenolol/chlorthalidone and 69% for lisinopril/hydrochlorothiazide. All three active treatments were tolerated well.
  
  
  CONCLUSIONS
  This study demonstrates that the low-dose combination sustained-release verapamil/trandolapril may be a suitable alternative for combinations containing a thiazide diuretic or a beta-blocker for longer term management of hypertensive patients for whom combination therapy is indicated.
authors.affiliation: Department of Internal Medicine, University Hospital, Maastricht, The Netherlands.
authors.forename: P W
authors.initials: PW
authors.lastname: de Leeuw
authors.forename: T
authors.initials: T
authors.lastname: Notter
authors.forename: P
authors.initials: P
authors.lastname: Zilles
mesh_terms: D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001262:Atenolol / Q000008:administration & dosage; D001794:Blood Pressure / Q000187:drug effects; D002752:Chlorthalidone / Q000008:administration & dosage; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D004338:Drug Combinations; D004361:Drug Tolerance; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007211:Indoles / Q000008:administration & dosage; D017706:Lisinopril / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D012449:Safety; D014700:Verapamil / Q000008:administration & dosage
chemical_list: D000959:Antihypertensive Agents; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D007211:Indoles; D006852:Hydrochlorothiazide; C052035:trandolapril; D001262:Atenolol; D014700:Verapamil; D017706:Lisinopril; D002752:Chlorthalidone