Amelioration of arterial properties with a perindopril-indapamide very-low-dose combination

Epidemiological studies have shown that increased arterial stiffness and wave reflections, major determinants of systolic and pulse pressure, are associated with morbidity and mortality. Therapeutic trials based on cardiovascular mortality have recently shown that reduction of systolic blood pressure (SBP) requires normalization of both large-artery stiffness and wave reflections.

To compare the antihypertensive effects of the very-low-dose combination of perindopril (2 mg) and indapamide (0.625 mg) (one or two tablets per day) with the beta-blocking agent atenolol (50 mg; one or two tablets per day) in order to determine whether the combination decreased SBP and pulse pressure more than did atenolol, and whether this decrease occurred in relation to a reduction in arterial stiffness [aortic pulse wave velocity (PWV)] or a decrease in the intensity of, or delay in, wave reflections (augmentation index, measured by applanation tonometry) or a combination of both.

This was a double-blind randomized study in 471 individuals with essential hypertension followed for 12 months. Arterial pressure was measured in the brachial artery (mercury sphygmomanometer) and in the carotid artery (applanation tonometry).

For the same reduction in diastolic blood pressure (DBP), the combination of perindopril and indapamide decreased brachial SBP and pulse pressure significantly more than did atenolol (adjusted differences between groups -6.2 +/- 1.5 and -5.5 +/- 1.0 mmHg, respectively; P < 0.001). This difference was even more pronounced for the carotid than for the brachial artery. Whereas both antihypertensive agents similarly decreased PWV, only the combination significantly attenuated wave reflections.

Normalization of SBP, pulse pressure and arterial function--a haemodynamic profile known to improve survival significantly in hypertensive populations at high cardiovascular risk--was achieved to a greater extent with a very-low-dose combination of perindopril and indapamide than with atenolol.