A DOSE-RESPONSE STUDY OF PERINDOPRIL IN HYPERTENSION. EFFECTS ON BLOOD PRESSURE 6 AND 24 H AFTER DOSING.

Angiotensin-converting enzyme (ACE) inhibitors have achieved wide acceptance in the treatment of hyper-tension both as monotherapy and in combination with other agent. The antihypertensive effects of different doses of perindopril were compared using a randomized placebo-controlled design .All patients initially entered a four-week , single-blind placebo run-in period. The mean supine diastolic blood pressure was between 95 and 114 mmHg after four weeks, patients were randomized to 12 weeks of  therapy with perindopril 2, 4, 8 or 16 mg or matching placebo, each given once daily in the morning. Patients were seen weekly for four weeks and then every two weeks for the last eight weeks of the double-blind phase.
Of a total of 300 patients entered into the study, 249 were eligible or randomization to perindopril 2, 4, 8 or 16 mg or placebo at the end of the four-week placebo run-in period .All five groups (perindopril 2, 4, 8 and 16 mg and placebo) had similar characteristics at baseline. Randomization of patients to four different doses, of perindopril or to placebo resulted in similar mean systolic and diastolic blood pressure values at baseline for each subgroup. At the final visit, Perindopril 2 mg once daily significantly (P< 0.05) lowered diastolic blood pressure versus baseline 24 h after tablet administration. Dose of perindopril 4 mg daily or greater also lowered blood pressure significantly (p < 0.05) more than did placebo (Table 2). Dose of perindopril up to 8 mg caused a progressive decrease in placebo-corrected blood pressure at 24 h , with changes at the 16 mg dose exerting no additional effect.
Changes in blood pressure at 6 h, the time of perindopril's peak antihypertensive effect, were similar in magnitude to those noted at 24 h. Perindopril 2 mg significantly reduced diastolic blood pressure versus baseline , with higher doses up to 8 mg daily causing a further reduction in diastolic blood pressure , which was significantly different from placebo.