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

Objective To compare the therapeutic coverage and safety of amlodipine and perindopril in patients with mild to moderate hypertension (diastolic blood pressure greater than or equal to 90 mmHg and less than or equal to 109 mm Hg). Design A double-blind, randomized, parallel-group, multicentre study. Metho ds Following a 2-week placebo wash-out period, the patients were randomly a llocated to treatment with either amlodipine at 5-10 mg once a day or perin dopril at 4-8 mg once a day, for 60 days. Trough : peak ratios were calcula ted by two different methods (global and individualized approaches) from 24 h ambulatory blood pressure recordings made after the placebo period and a fter 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 through out the study. Results The placebo-adjusted, global, diastolic blood pressure trough : pea k ratio was 0.80 in the amlodipine group (n = 47) and 0.81 in the perindopr il group (n = 49) in an intent-to-treat analysis. The corresponding global systolic blood pressure trough : peak ratio was 0.83 for amlodipine and 0.6 8 for perindopril. Individual trough : peak ratios were non-normally distri buted. Mean (+/- SD) individual trough : peak ratios (intent-to-treat analy sis) for diastolic 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 am lodipine and 0.01 +/- 3.90 for perindopril (median 0.21). Both treatments p roduced comparable decreases in clinic systolic and diastolic blood pressur e between days 0 and 60. Forty-eight hours after the last dose, both systol ic and diastolic blood pressure were lower in amlodipine-treated patients t han 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 ambu latory blood pressure trough : peak ratios showed very large variations. De termination of trough : peak ratios by the conventional approach or by an i ndividual approach can yield disparate values. After omitting one dose, a c ondition imitating noncompliance, blood pressure was more effectively contr olled with amlodipine than with perindopril. J Hypertens 1999, 17:137-146 ( C) Lippincott Williams & Wilkins.