title: Double-blind, randomized, multicentre comparison of the effects of amlodipine and perindopril on 24 h therapeutic coverage and beyond in patients with mild to moderate hypertension. General Physicians Investigators' Group.
abstract: OBJECTIVE
  To compare the therapeutic coverage and safety of amlodipine and perindopril in patients with mild to moderate hypertension (diastolic blood pressure > or = 90 mmHg and < or = 109 mmHg).
  
  
  METHODS
  A double-blind, randomized, parallel-group, multicentre study.
  
  
  METHODS
  Following a 2-week placebo wash-out period, the patients were randomly allocated to treatment with either amlodipine at 5-10 mg once a day or perindopril at 4-8 mg once a day, for 60 days. Trough: peak ratios were calculated by two different methods (global and individualized approaches) from 24 h ambulatory blood pressure recordings made after the placebo period and after the active treatment period. Residual lowering of blood pressure after single-blind, single-dose omission was also investigated with further 24 h ambulatory blood pressure monitoring. Safety assessments were made throughout the study.
  
  
  RESULTS
  The placebo-adjusted, global, diastolic blood pressure trough: peak ratio was 0.80 in the amlodipine group (n = 47) and 0.81 in the perindopril group (n = 49) in an intent-to-treat analysis. The corresponding global systolic blood pressure trough: peak ratio was 0.83 for amlodipine and 0.68 for perindopril. Individual trough: peak ratios were non-normally distributed. Mean (+/- SD) individual trough: peak ratios (intent-to-treat analysis) for diatolic blood pressure were 0.50 +/- 0.69 for amlodipine (median 0.42) and 0.15 +/- 3.27 for perindopril (median 0.33). In the per protocol analysis, the corresponding values were 0.50 +/- 0.72 (median 0.34) for amlodipine and 0.01 +/- 3.90 for perindopril (median 0.21). Both treatments produced comparable decreases in clinic systolic and diastolic blood pressure between days 0 and 60. Forty-eight hours after the last dose, both systolic and diastolic blood pressure were lower in amlodipine-treated patients than perindopril-treated patients. Amlodipine and perindopril were generally well tolerated. The most frequently reported adverse event was leg oedema in amlodipine-treated patients (19.1%), and coughing in perindopril-treated patients (14.3%).
  
  
  CONCLUSIONS
  These results showed no statistically significant difference in trough: peak ratios between amlodipine and perindopril. However, the ambulatory blood pressure trough: peak ratios showed very large variations. Determination of trough: peak ratios by the conventional approach or by an individual approach can yield disparate values. After omitting one dose, a condition imitating noncompliance, blood pressure was more effectively controlled with amlodipine than with perindopril.
authors: Centre d'Investigation Clinique de Nancy, INSERM-Centre Hospitalier Universitaire, Nancy, France. f.zannad@chu-nancy.fr
authors: F
authors: F
authors: Zannad
authors: C M
authors: CM
authors: Bernaud
authors: R
authors: R
authors: Fay
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D017311:Amlodipine / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D018660:Blood Pressure Monitoring, Ambulatory; D002940:Circadian Rhythm / Q000502:physiology*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020913:Perindopril; D011379:Prognosis; D012449:Safety
chemical_list: D000959:Antihypertensive Agents; D007211:Indoles; D017311:Amlodipine; D020913:Perindopril