CLINICAL RESEARCH: HYPERTENSION
Aliskiren, an Oral Renin Inhibitor, Provides Dose-Dependent Efficacy and Sustained 24-HourBlood Pressure Control in Patients With Hypertension
Byung-Hee Oh, MD, PhD, FACC*,
Jerry Mitchell, MD, PhD , ,
James R. Herron, MD ,
Jenny Chung, PharmD||,
Mahmudul Khan, PhD|| and
Deborah L. Keefe, MD, MPH, FACC||,*
* 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 |
|
Related Article
-
Do We Need Yet Another Blocker of the Renin-Angiotensin System?
- Franz H. Messerli and Richard N. Re
J. Am. Coll. Cardiol. 2007 49: 1164-1165.
[Full Text]
[PDF]
This article has been cited by other articles:
|
|
|
|
 
S. Perlini, F. Salinaro, and M. L. Fonte
Direct Renin Inhibition: Another Weapon to Modulate the Renin-Angiotensin System in Postinfarction Remodeling?
Hypertension,
December 1, 2008;
52(6):
1019 - 1021.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Krop, I. M. Garrelds, R. J.A. de Bruin, J. M.G. van Gool, N. D.L. Fisher, N. K. Hollenberg, and A.H. Jan Danser
Aliskiren Accumulates in Renin Secretory Granules and Binds Plasma Prorenin
Hypertension,
December 1, 2008;
52(6):
1076 - 1083.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Dietz, R. Dechend, C.-M. Yu, M. Bheda, J. Ford, M. F. Prescott, and D. L. Keefe
Effects of the direct renin inhibitor aliskiren and atenolol alone or in combination in patients with hypertension1
Journal of Renin-Angiotensin-Aldosterone System,
September 1, 2008;
9(3):
163 - 175.
[Abstract]
[PDF]
|
|
|
|
|
|
|
S. Ayalasomayajula, C.-M. Yeh, S. Vaidyanathan, B. Flannery, H. A. Dieterich, D. Howard, M. P. Bedigian, and W. P. Dole
Effects of Aliskiren, a Direct Renin Inhibitor, on Cardiac Repolarization and Conduction in Healthy Subjects
J. Clin. Pharmacol.,
July 1, 2008;
48(7):
799 - 811.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. J. Danser and G. Nguyen
Spotlight on Renin: The Renin Academy Summit: advancing the understanding of renin science
Journal of Renin-Angiotensin-Aldosterone System,
June 1, 2008;
9(2):
119 - 123.
[PDF]
|
|
|
|
|
|
|
J. M. C. Connell, S. M. MacKenzie, E. M. Freel, R. Fraser, and E. Davies
A Lifetime of Aldosterone Excess: Long-Term Consequences of Altered Regulation of Aldosterone Production for Cardiovascular Function
Endocr. Rev.,
April 1, 2008;
29(2):
133 - 154.
[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]
|
|
|
|
|
|
|
Other articles noted
Evid. Based Med.,
August 1, 2007;
12(4):
127 - 128.
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. H. Messerli and R. N. Re
Do We Need Yet Another Blocker of the Renin-Angiotensin System?
J. Am. Coll. Cardiol.,
March 20, 2007;
49(11):
1164 - 1165.
[Full Text]
[PDF]
|
|
|
|
