Central Pressure and Biomarker Responses to Renin Inhibition with Hydrochlorothiazide and Ramipril in Obese Hypertensives: The ATTAIN Study

Abstract

Background/Aims: In obese, hypertensive subjects, the renin-angiotensin system (RAS) is enhanced and natriuresis impaired, suggesting a role for combination RAS blockade with diuretics. Data suggest that renin inhibition may attenuate diuretic-induced RAS activation and oxidative stress. Methods: In this 8-week, double-blind study of 386 obese individuals (mean body mass index: 35.3) with stage 2 hypertension (mean age: 54.9 years; mean sitting systolic blood pressure, SBP: ≧160 but <200 mm Hg), we compared the efficacy of aliskiren + hydrochlorothiazide (HCTZ) in reducing blood pressure (BP), plasma renin activity (PRA), and a urinary marker of oxidative stress to ramipril. Subjects were randomized to aliskiren/HCTZ 150/12.5 mg or ramipril 5 mg for 1 week, and after the 1st week force titrated to aliskiren/HCTZ 300/25 mg or ramipril 10 mg for 7 weeks. Results: After 8 weeks, aliskiren/HCTZ provided greater reductions in office BP than ramipril (–28.1/–10.1 vs. –16.6/–3.6 mm Hg, p < 0.0001) as well as 24-hour ambulatory and central pressure measures. Aliskiren/HCTZ also lowered PRA (–45 vs. +83%) and the urinary F2-isoprostane/creatinine ratio (–18 vs. +7%) to a greater extent than ramipril. Adverse events (AEs) were similar in the two groups (35.8% with aliskiren/HCTZ vs. 37.3% on ramipril reporting at least one AE). Conclusions: Our findings suggest that the aliskiren/HCTZ combination reduced BP, PRA, and isoprostanes to a greater extent than did ramipril in obese patients with stage 2 hypertension.