Published Online
on March 12, 2007

A more recent version of this article appeared on May 1, 2007

This Article Full Text (PDF) All Versions of this Article: 49/5/1047    most recent HYPERTENSIONAHA.106.084301v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jordan, J. Articles by Keefe, D. L. Search for Related Content PubMed PubMed Citation Articles by Jordan, J. Articles by Keefe, D. L. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB AMLODIPINE BESYLATE HYDROCHLOROTHIAZIDE Medline Plus Health Information High Blood Pressure Obesity Related Collections Obesity Other hypertension Clinical Studies

Submitted on November 9, 2006
Revised on December 5, 2006

Direct Renin Inhibition With Aliskiren in Obese Patients With Arterial Hypertension

Jens Jordan^*; Stefan Engeli; Sam W. Boye; Stephanie Le Breton; and 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.

^* To whom correspondence should be addressed. E-mail: jens.jordan{at}charite.de.

Abstract--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

This article has been cited by other articles:

				K. Andersen, M. H Weinberger, C. M Constance, M. A Ali, J. Jin, M. F Prescott, and D. L Keefe Comparative effects of aliskiren-based and ramipril-based therapy on the renin system during long-term (6 months) treatment and withdrawal in patients with hypertension Journal of Renin-Angiotensin-Aldosterone System, September 1, 2009; 10(3): 157 - 167. [Abstract] [PDF]

				P. S Sever, A. H Gradman, and M. Azizi Managing cardiovascular and renal risk: the potential of direct renin inhibition Journal of Renin-Angiotensin-Aldosterone System, June 1, 2009; 10(2): 65 - 76. [Abstract] [PDF]

				J. Basile Blood pressure responder rates versus goal rates: which metric matters? Therapeutic Advances in Cardiovascular Disease, April 1, 2009; 3(2): 157 - 174. [Abstract] [PDF]

				D. S. Nuzum and T. Merz Macrovascular Complications of Diabetes Mellitus Journal of Pharmacy Practice, April 1, 2009; 22(2): 135 - 148. [Abstract] [PDF]

				{blacktriangledown}Aliskiren for hypertension in adults DTB, October 1, 2008; 46(10): 73 - 76. [Abstract] [Full Text] [PDF]

				M. J. Brown Aliskiren Circulation, August 12, 2008; 118(7): 773 - 784. [Abstract] [Full Text] [PDF]

				A. H. Gradman and R. Kad Renin inhibition in hypertension. J. Am. Coll. Cardiol., February 5, 2008; 51(5): 519 - 528. [Abstract] [Full Text] [PDF]

				I. Biaggioni Should We Target the Sympathetic Nervous System in the Treatment of Obesity-Associated Hypertension? Hypertension, February 1, 2008; 51(2): 168 - 171. [Full Text] [PDF]

				A. Seed, R. Gardner, J. McMurray, C. Hillier, D. Murdoch, R. MacFadyen, A. Bobillier, J. Mann, and T. McDonagh Neurohumoral effects of the new orally active renin inhibitor, aliskiren, in chronic heart failure Eur J Heart Fail, November 1, 2007; 9(11): 1120 - 1127. [Abstract] [Full Text] [PDF]