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(Hypertension. 2007;49:1047.)
© 2007 American Heart Association, Inc.

Original Articles

Direct Renin Inhibition With Aliskiren in Obese Patients With Arterial Hypertension

Jens Jordan; Stefan Engeli; Sam W. Boye; Stephanie Le Breton; Deborah L. Keefe

From the Franz-Volhard Clinical Research Center (J.J., S.E.), Medical Faculty of the Charité and Helios Klinikum, Berlin, Germany; Novartis Pharmaceuticals Corporation (S.W.B., D.L.K.), East Hanover, NJ; and Novartis Pharma AG (S.L.B.), Basel, Switzerland.

Correspondence to Jens Jordan, Franz-Volhard Clinical Research Center, Haus 129, Charité Campus Buch, Wiltbergstrasse 50, 13125 Berlin, Germany. E-mail jens.jordan{at}charite.de

Current guidelines from the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure recommend first-line treatment with a thiazide diuretic but do not provide specific guidance for obese patients. The renin system is activated in obesity-associated arterial hypertension. Therefore, we tested the hypothesis that the oral direct renin inhibitor aliskiren could provide additive blood pressure lowering in obese patients with hypertension (body mass index 30 kg/m²; mean sitting diastolic blood pressure: 95 to 109 mm Hg) who had not responded to 4 weeks of treatment with hydrochlorothiazide (HCTZ) 25 mg. After a 2- to 4-week washout, 560 patients received single-blind HCTZ (25 mg) for 4 weeks; 489 nonresponders were randomly assigned to double-blind aliskiren (150 mg), irbesartan (150 mg), amlodipine (5 mg), or placebo for 4 weeks added to HCTZ (25 mg), followed by 8 weeks on double the initial doses of aliskiren, irbesartan, or amlodipine. After 8 weeks of double-blind treatment (4 weeks on the higher dose), aliskiren/HCTZ lowered blood pressure by 15.8/11.9 mm Hg, significantly more (P<0.0001) than placebo/HCTZ (8.6/7.9 mm Hg). Aliskiren/HCTZ provided blood pressure reductions similar to those with irbesartan/HCTZ and amlodipine/HCTZ (15.4/11.3 and 13.6/10.3 mm Hg, respectively), with similar tolerability to placebo/HCTZ. Adverse event rates were highest with amlodipine/HCTZ because of a higher incidence of peripheral edema (11.1% versus 0.8% to 1.6% in other groups). In conclusion, combination treatment with aliskiren is a highly effective and well-tolerated therapeutic option for obese patients with hypertension who fail to achieve blood pressure control with first-line thiazide diuretic treatment.

Key Words: direct renin inhibitor • Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure 7 • obesity • renin–angiotensin system • thiazide diuretic

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