The Influence of Perindopril and the Diuretic Combination Amiloride+hydrochlorothiazide on the Vessel Wall Properties of Large Arteries in Hypertensive Patients

Objective: To compare the cardiovascular effects of 6 months of treatment with the angiotensin converting enzyme inhibitor perindopril and with the diuretic combination amiloride+hydrochlorothiazide, and to study possible persistence of observed treatment effects after discontinuation of antihypertensive therapy.

Design: A placebo run-in period preceded a 6-month active-treatment phase in 41 patients with essential hypertension, according to a double-blind, randomized, parallel-group design. Patients received either 4 mg perindopril or 2.5/25 mg amiloride+hydrochlorothiazide once a day. Patients were then studied for a 3-month single-blind placebo run-out period.

Results: After 6 months of treatment, systolic blood pressure was reduced significantly by perindopril (supine by 11%, sitting by 10%) and by amiloride+hydrochlorothiazide (supine by 8%, sitting by 12%). Diastolic blood pressure was also decreased significantly by perindopril (supine by 8%, sitting by 11%) and by amiloride+hydrochlorothiazide (supine by 4%, sitting by 9%). Mean arterial pressure decreased significantly during treatment with perindopril (by 9%) and with amiloride+hydrochlorothiazide (by 6%). Cardiac index increased with perindopril (by 6%), because of an increased stroke index (by 5%), but amiloride+hydrochlorothiazide did not change cardiac function. Systemic vascular resistance index decreased significantly more with perindopril (by 14%) than with amiloride+hydrochlorothiazide (by 8%). The distensibility of the common carotid artery was significantly enhanced by perindopril (by 16%), but not changed by amiloride+hydrochlorothiazide (1% difference). The difference between perindopril and amiloride+hydrochlorothiazide for carotid distensibility was statistically significant. The compliance of the common carotid artery tended to be increased more by perindopril (by 7%) than by amiloride+hydrochlorothiazide, which induced a 5% decrease in carotid compliance. After withdrawal of therapy, for both drugs, all treatment-induced changes were reversed to pretreatment values within 7 weeks.

Conclusion: The distensibility of the elastic common carotid artery was increased by perindopril, but not by amiloride+hydrochlorothiazide. Large-artery properties of the muscular arteries and systemic vascular resistance improved with both drugs, but in general the changes were more pronounced with perindopril than with amiloride+hydrochlorothiazide. The present results indicate a more pronounced effect of perindopril at both macro- and microcirculatory levels, which will consequently lead to a larger decrease in cardiac afterload. After discontinuation of therapy all parameters returned to baseline values within 7 weeks.