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CLINICAL RESEARCH: HYPERTENSION

Aliskiren, an Oral Renin Inhibitor, Provides Dose-Dependent Efficacy and Sustained 24-Hour Blood Pressure Control in Patients With Hypertension

Byung-Hee Oh, MD, PhD, FACC^_*, Jerry Mitchell, MD, PhD^,, James R. Herron, MD, Jenny Chung, PharmD^||,a, Mahmudul Khan, PhD^||,a and Deborah L. Keefe, MD, MPH, FACC^||,a,_*

^_* Seoul National University Hospital, Seoul, Korea
Texas Center for Drug Development, Houston, Texas
Baylor College of Medicine, Houston, Texas
James R. Herron, MD, Ltd., Chicago, Illinois
^|| Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.

Manuscript received June 27, 2006; revised manuscript received October 19, 2006, accepted November 6, 2006.

^_* Reprint requests and correspondence: Dr. Deborah L. Keefe, Novartis Pharmaceuticals Corporation, Clinical Research and Development, 502/228, One Health Plaza, East Hanover, New Jersey 07936. (Email: deborah.keefe{at}novartis.com).

Objectives: This dose-ranging study evaluated the antihypertensive efficacy and tolerability of aliskiren in patients with mild-to-moderate hypertension.

Background: Low blood pressure (BP) control rates among patients with hypertension indicate a need for improved treatment options. This study investigates aliskiren, the first in a new antihypertensive class called renin inhibitors.

Methods: Patients with mean sitting diastolic BP 95 to 109 mm Hg were randomized to aliskiren 150, 300, or 600 mg or placebo once daily for 8 weeks. Patients completing this treatment phase entered a 2-week treatment-free withdrawal period. Office BP was recorded at baseline, weeks 2, 4, 6, and 8 of treatment, and 4 days and 2 weeks after cessation of treatment. A subgroup of patients underwent ambulatory BP monitoring.

Results: In total, 672 patients were randomized to treatment. After 8 weeks, aliskiren 150, 300, and 600 mg significantly reduced mean sitting BP (systolic/diastolic) by 13.0/10.3, 14.7/11.1, and 15.8/12.5 mm Hg, respectively, versus 3.8/4.9 mm Hg with placebo (all p < 0.0001 for systolic and diastolic BP). The BP-lowering effect of aliskiren persisted for up to 2 weeks after treatment withdrawal. Aliskiren significantly reduced mean 24-h ambulatory BP (p < 0.0001 vs. placebo with all doses) exhibiting smooth, sustained effects and high trough-to-peak ratios. Aliskiren was well tolerated; overall adverse event rates were 40.1%, 46.7%, and 52.4% with aliskiren 150, 300, and 600 mg, respectively, and 43.0% with placebo. Few patients discontinued treatment due to adverse events.

Conclusions: Aliskiren provides significant antihypertensive efficacy in patients with hypertension, with no rebound effects on blood pressure after treatment withdrawal.

Abbreviations and Acronyms   ABPM = ambulatory blood pressure monitoring   AE = adverse event   ARB = angiotensin receptor blocker   BP = blood pressure   ITT = intent-to-treat   LSM = least squares mean   maDBP/maSBP = mean ambulatory diastolic/systolic blood pressure   msDBP/msSBP = mean sitting diastolic/systolic blood pressure   PRA = plasma renin activity   RC = renin concentration

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