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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. ©2011 Wiley Periodicals, Inc.