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

ABSTRACT: 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.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.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).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.

SUBMITTER: Whaley-Connell A

PROVIDER: S-EPMC3101521 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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

Whaley-Connell Adam A Purkayastha Das D Yadao Anthony A Sowers James R JR

Cardiorenal medicine 20110117 1

<h4>Background/aims</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 22258466

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Project description:ObjectiveThe main objective of this study was to evaluate non-inferiority of office mean systolic blood pressure (BP) reduction efficacy and superiority of 24-hour ambulatory central BP reduction efficacy between losartan combined with fixed dose amlodipine (L/A group) and dose up-titrated hydrochlorothiazide (L/H group) according to office BP.MethodsWe conducted a prospective, randomized, double-blind multicenter trial in 231 patients with hypertensive (mean age = 59.2 ± 12.2 years). Patients received losartan 50 mg monotherapy for 4 weeks, followed by additional use of amlodipine 5 mg or hydrochlorothiazide 12.5 mg for 20 weeks after randomization. The patients who did not achieve the BP goal after 4 weeks' randomization received an increased dose of 100 mg/5 mg for the L/A group and 100 mg/25 mg for L/H group, respectively. The 24-hour ambulatory central BP was measured at baseline and after 20 weeks' treatment.ResultsOffice mean systolic BP reduction of L/A group was not inferior to L/H group after 4 weeks' treatment (-17.6 ± 13.3 vs. -14.4 ± 12.6 mm Hg, P = 0.0863) and was not significantly different after 20 weeks' treatment. (-15.7 ± 14.0 vs. -14.7 ± 15.1 mm Hg, P = 0.6130) The 24-hour ambulatory central systolic BP was significantly more reduced in the L/A group compared with that in the L/H group after 20 weeks' treatment (-9.37 ± 10.67 vs. -6.28 ± 10.50 mm Hg, P = 0.0407). The 24-hour ambulatory central systolic BP at the completion of the study and its reduction magnitude were independently associated with reductions in aortic pulse wave velocity, pulse pressure, and wave reflection magnitude.ConclusionOffice systolic BP reduction with L/A was not inferior to L/H after 4 week's treatment. The combination of losartan and amlodipine was more favorable in 24-hour ambulatory central hemodynamics beyond BP-lowering efficacy than the combination of losartan and hydrochlorothiazide, regardless of office BP.Clinical trials registrationNCT02294539.

Project description:BackgroundSystolic hypertension is the most common form of hypertension in elderly patients. There is increasing evidence that measurement of central aortic pressure (CAP) better accounts for cardiovascular risk than brachial blood pressure (BP). The Aliskiren for GEriatric LowEring of SyStolic hypertension (AGELESS) study in elderly patients with systolic hypertension showed that aliskiren-based therapy provided greater reductions in peripheral BP than ramipril-based therapy over 12 and 36 weeks of treatment. Here, we present CAP results in a substudy of elderly patients from the AGELESS study.MethodsThis was a post hoc analysis of a 36-week, randomized, double-blind, parallel-group, active-controlled, optional-titration study in patients ≥65 years of age with systolic BP ≥140 mmHg. Changes in both central and peripheral BP and pulse pressure (PP) and changes in systolic and PP amplification ratios from baseline to the week 36 end point with aliskiren-based versus ramipril-based therapy were analyzed.ResultsOf the 901 patients randomized in the overall study, 154 patients (aliskiren, n=78; ramipril, n=76) had CAP data. Numerically comparable reductions were seen for central aortic systolic pressure (CASP) in aliskiren-based therapy (baseline: 143.7±15.0; week 36: -20.3±16.2) compared with ramipril-based therapy (baseline: 147.9±11.9; week 36: -20.7±14.6). However, for the change in central aortic diastolic pressure, the least squares mean between-treatment difference (-3.6 mmHg [95% confidence interval, -6.76, -0.43; P=0.0263]) was in favor of aliskiren, while the other changes were comparable between the two groups with a trend in favor of aliskiren for CASP as well (-2.6 mmHg [95% confidence interval, -7.38, 2.19; P=0.2855)]. Correlation coefficients for change from baseline between CASP and systolic BP and between central aortic pulse pressure and PP (r=0.8, P<0.0001) were highly significant.ConclusionAliskiren-based therapy provides comparable reductions in CASP to ramipril-based therapy. Although the results did not reach statistical significance, these findings, when coupled with those of the main study, suggest that aliskiren may offer effective control of central BP in elderly patients with systolic hypertension and may be a good alternative to ramipril.

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Dataset Information

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

Publications

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

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