Peripheral and Central Blood Pressure Responses of Combination Aliskiren/Hydrochlorothiazide and Amlodipine Monotherapy in African American Patients With Stage 2 Hypertension: The ATLAAST Trial

Abstract

Efficacy of antihypertensive agents on central blood pressure (BP) in African Americans is not well studied. The authors report on an 8-week double-blind, randomized study of African American patients with stage 2 hypertension that compared brachial and central BP responses (substudy of 53 patients) to combination aliskiren ⁄ hydrochlorthiazide (HCTZ) and amlodipine monotherapy. Following a 1-to 4-week washout, initial therapy was aliskiren ⁄ HCTZ 150 ⁄ 12.5 mg (n=166) or amlodipine 5 mg (n=166) for 1 week, forced-titrated to aliskiren ⁄ HCTZ 300 ⁄ 25 mg or amlodipine 10 mg for 7 weeks. Mean seated systolic BP reductions from baseline was similar with both treatments ()28.6 mm Hg with aliskiren ⁄ HCTZ vs )28.2 mm Hg with amlodipine). In the substudy, significantly greater reductions in central systolic BP was observed with aliskiren ⁄ HCTZ vs amlodipine ()30.1 mm Hg vs )21.2; P=.031), although 24-hour mean ambulatory BP reductions between the two groups were similar. Central pressure is considered an important risk factor in African Americans, and these findings may suggest a new treatment option for these patients. J Clin Hypertens (Greenwich). 2011;13:366-375. Ó2011 Wiley Periodicals, Inc.African American adults have a greater prevalence of hypertension, an earlier onset, greater pressure-related end organ damage, and low blood pressure (BP) control rates compared with their white American counterparts (32% vs 23%).1,2 In addition, African Americans have diffuse macrovascular and microvascular dysfunction manifesting as increased stiffness of the carotid artery and aorta, 3,4 heightened-resistance artery constriction, and blunted-resistance artery dilation, 5 all of which correlate directly with end organ damage. 6,7 Although the prognostic value of brachial BP for future cardiovascular events has been well established, arterial stiffness and microvascular dysfunction significantly influence central BP, while brachial pressure is less influenced by these changes. 8The findings from the Strong Heart Study, which noninvasively determined central pulse pressure is more strongly related to vascular hypertrophy, extent of atherosclerosis, and cardiovascular events than is brachial BP, support the use of central pressure as a treatment target in clinical trials. 9 To date, findings from at least 7 longitudinal studies show that central BP is a stronger predictor of cardiovascular outcomes than brachial pulse pressure. 8,10 Although prospective data are needed, central BP may be pathophysiologically more relevant than peripheral (brachial) BP in the pathogenesis of cardiovascular disease.8 A recent study conducted in young (mean age, 21.7 years) and healthy (normotensive) African American and white men (mean age, 23.6 years) reported higher central BP and stiffer blood vessels in African American men compared with their white counterparts, signs that African American men are developing hypertension early and with few symptoms. 11Calcium channel antagonists and diuretics have long been preferred as an antihypertensive...

Aortic stiffness: pathophysiology, clinical implications, and approach to treatment

“…Another study known as EXPLOR (Amlodipine/Valsartan on Central Aortic Blood Pressure in Uncontrolled Essential Hypertension With Amlodipine 5 mg) compared amlodipine/valsartan therapy against amlodipine/atenolol, and concluded that the former combination achieved a significantly greater reduction in augmentation index and central blood pressure 33. The ATLAAST (Aliskiren/hydrochlorothiazide and amlodipine monotherapy in African American patients with stage 2 hypertension) trial34 compared the efficacy of aliskiren/hydrochlorothiazide therapy in an African American population diagnosed with stage II hypertension and concluded that renin inhibitor/diuretic-based therapy achieved a substantial reduction in central blood pressure as compared with amlodipine monotherapy. Another meta-analysis by Ong et al included 15 randomized, double-blind, parallel-group trials performed over 7 years and showed that angiotensin-converting enzyme inhibitors were superior to calcium channel blockers and placebo in reducing aortic stiffness 35.…”

Central Aortic Pressure, Arterial Compliance: Emerging Tools to Identify and Guide Therapy for High-Risk African American Patients

“…Thus, sodium intake, a modifi able factor, could be leveraged to improve cardiovascular risk through anticipated benefi cial effects on central and peripheral pulse pressures. In a substudy of African Americans with stage 2 hypertension, we found that treatment with an aliskiren/HCTZ combination approach, compared with amlodipine alone, produced similar reduction in brachial BP (offi ce and 24 h), but a significantly greater reduction of central systolic pressure that was 30 mmHg in the aliskiren/HCTZ group compared with 21 mmHg in the amlodipine group [ 48 ]. Beta blockers have fallen out of favor as an initial antihypertensive choice because of concerns about less effective stroke prevention, particularly in older people, compared with other agents that reduce BP to the same degree.…”

Evaluating interventions to reduce central aortic pressure, arterial stiffness and morbidity–mortality

“…Although mean seated SBP and DBP reductions from baseline were similar with both treatments, significantly greater reductions in central aortic SBP (P ¼ 0.031) were observed with aliskiren/HCTZ compared with amlodipine ( Fig. 2) [13].…”

“…CI, confidence interval; n, number of ITT patients with both baseline and endpoint nonmissing values. Last-observation-carried-forward (LOCF) approach is used[13]. Copyright ß (2011), with permission from John Wiley and Sons, and authors.…”