A dose-response study of perindopril in hypertension: effects on blood pressure 6 and 24 h after dosing. Perindopril Multicentre Dose-Response Study Group.

OBJECTIVE: To examine the dose-response characteristics of perindopril at the time of its peak and trough antihypertensive effects, with the primary outcome measure being changes in diastolic blood pressure. DESIGN: After a four-week, single-blind placebo run-in, patients were randomly allocated to four doses of perindopril or placebo using a parallel group design. SETTING: Sixteen specialist centres in the United States. PATIENTS: Of 483 patients entered into the run-in phase, 293 were eligible for randomization to perindopril or placebo therapy, with 260 patients included in the final efficacy analysis. INTERVENTIONS: Eligible patients were randomized to 12 weeks of therapy with perindopril 2, 4, 8 or 16 mg or placebo. MAIN RESULTS: At the final visit, all doses of perindopril significantly (P < 0.05) lowered diastolic blood pressure compared with placebo. The ratio of changes in placebo-corrected diastolic blood pressure at 24 versus 6 h for perindopril 2, 4 and 8 mg was 1.0, 1.0 and 0.97, respectively. The maximum antihypertensive effect was seen with perindopril 8 mg, with the 16 mg dose providing no additional response. Changes in systolic and diastolic blood pressure were similar. CONCLUSIONS: Perindopril is most effective at doses of 4 and 8 mg once daily, with similar reductions in diastolic blood pressure present at 6 and 24 h after dosing.