Improvement in Blood Pressure, Arterial Stiffness and Wave Reflections With a Very-Low-Dose Perindopril/Indapamide Combination in Hypertensive Patient

Abstract

Abstract-International guidelines recommend that antihypertensive drug therapy should normalize not only diastolic (DBP) but also systolic blood pressure (SBP). Therapeutic trials based on cardiovascular mortality have recently shown that SBP reduction requires normalization of both large artery stiffness and wave reflections. The aim of the present study was to compare the antihypertensive effects of the very-low-dose combination indapamide (0.625 mg) and perindopril (2 mg) (Per/Ind) with the ␤-blocking agent atenolol (50 mg) to determine whether Per/Ind decreases SBP and pulse pressure (PP) more than does atenolol and, if so, whether this decrease is predominantly due to reduction of aortic pulse wave velocity (PWV) (automatic measurements) and reduction of wave reflections (pulse wave analysis, applanation tonometry). In a double-blind randomized study, 471 patients with essential hypertension were followed for 12 months. For the same DBP reduction, Per/Ind decreased brachial SBP (Ϫ6.02 mm Hg; 95% confidence interval, Ϫ8.90 to Ϫ3.14) and PP (Ϫ5.57; 95% confidence interval, Ϫ7.70 to Ϫ3.44) significantly more than did atenolol. This difference was significantly more pronounced for the carotid artery than for the brachial artery. Whereas the 2 antihypertensive agents decreased PWV to a similar degree, only Per/Ind significantly attenuated carotid wave reflections, resulting in a selective decrease in SBP and PP. The very-low-dose combination Per/Ind normalizes SBP, PP, and arterial function to a significantly larger extent than does atenolol, a hemodynamic profile that is known to improve survival in hypertensive populations with high cardiovascular risk. Key Words: antihypertensive therapy Ⅲ pulse wave velocity Ⅲ pulse pressure R ecent epidemiological studies and recommendations of hypertension guidelines 1-3 have directed attention to systolic blood pressure (SBP) as a better guide than DBP for evaluating cardiovascular risk. It has been shown that drug therapy of hypertension frequently results in an adequate control of DBP (Յ90 mm Hg), whereas the ability to control SBP (Յ140 mm Hg) is achieved less often. 4,5 Such results have focused attention on hemodynamic factors, such as large artery stiffness and wave reflections, which are important determinants of SBP and pulse pressure (PP) and are strong independent cardiovascular risk predictors in hypertensive populations. Consequently, the role of drugs or regimens that may selectively reduce SBP and PP assumes importance.Very-low-dose combinations involving an ACE inhibitor (ACEI) and a diuretic (D) may be suitable for reducing SBP and PP and, at the same time, for facilitating the compliance with long-term drug treatment. 2,3,6 -8 In genetic models of hypertension in rats, the ACEI ϩ D combination was shown to induce a significantly more pronounced pressure-independent decrease in arterial stiffness and reduction of aortic collagen accumulation than that of each component given alone. 9,10 In middle-aged patients with hypertension, although D induces only mi...

Elevated circulating endothelial microparticles and brachial–ankle pulse wave velocity in well-controlled hypertensive patients

“…It is potential that the beneficial effects on vascular homoestasis can occur with or without a fall in cuff BP of the brachial artery and may explain the pressure-independent effects of some drugs, such as angiotensin converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB) and calcium channel blocker (CCB). [2][3][4][5]36 Therefore, optimal treatment of high BP should include evaluation of arterial elasticity, augmentation index of aortic pressure and left ventricular wasted energy, all of which should be reduced to the lowest level.…”

“…1 Although antihypertensive pharmacotherapy with the specific and arbitrary goal to modify BP profiles significantly reduced vascular events, emerging evidence indicates that with equivalent effects on lowering blood pressure, some but not all antihypertensive agents, lead to more reduction of vascular events. 2,3 This apparently beneficial effects beyond BP lowering may be, at least in part, because of further improvement of agent-related vascular properties, [2][3][4][5][6] suggesting that the evaluation of vascular function may be useful complement to brachial BP levels, and may provide more sensitive and specific markers for the vascular risk stratification.…”

The association between aortic augmentation index and cardiovascular risk factors in a large unselected population

“…AIx is fairly easily measured by applanation tonometry and therefore less time consuming than measuring PWV; 2 in addition, AIx may be modifiable to a higher degree than PWV. 3,4 However, concerns have been raised as to whether AIx is a reliable measurement of vascular compliance in the elderly 5,6 due to the curvilinear association between AIx and age. 6,7 Interestingly, findings have been contradictory regarding AIx as predictor of CVD where AIx has been associated with increased risk of CVD in highrisk populations 8,9 and in men, 10,11 while its use as a predictor in women 12,13 and in the general population is less certain.…”

Efficacy of very low dose perindopril 2 mg/indapamide 0.625 mg combination on left ventricular hypertrophy in hypertensive patients: the P.I.C.X.E.L. study rationale and design

“…The very low-dose combination perindopril 2 mg (ACE inhibitor)/Indapamide 0.625 mg (diuretic) combination (Per/Ind) Per 2/Ind 0.625 mg has shown a superior antihypertensive efficacy in comparative study vs atenolol, losartan and irbesartan [19][20][21][22][23] and studies in elderly patients and patients with renal impairments. 24,25 In long-term studies (1 year), Per/Ind combination has demonstrated a sustained efficacy with a high normalisation rate and a superiority to atenolol on systolic mean and pulse pressure.…”

“…24,25 In long-term studies (1 year), Per/Ind combination has demonstrated a sustained efficacy with a high normalisation rate and a superiority to atenolol on systolic mean and pulse pressure. 19,26,27 In different pharmacological models of LVH, Per/Ind combination has shown its capacity to reverse left ventricular mass. [28][29][30][31] A preliminary double-blind controlled study comparing the lowdose combination Per/Ind and atenolol has shown the higher capacity of Per/Ind to decrease the LVM in hypertensive patients.…”