Circulation. 2004;109:2492-2499
doi: 10.1161/01.CIR.0000131449.94713.AD
doi: 10.1161/01.CIR.0000131449.94713.AD
(Circulation. 2004;109:2492-2499.)
© 2004 American Heart Association, Inc.
Review: Current Perspective |
Combined Blockade of the Renin-Angiotensin System With Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Type 1 Receptor Antagonists
From the Clinical Investigation Center 9201, Assistance Publique des Hôpitaux de Paris/INSERM, Hôpital Européen Georges Pompidou, Paris, France.
Correspondence to Michel Azizi, MD, PhD, Clinical Investigation Center, Hôpital Européen Georges Pompidou, 20-40 rue Leblanc, 75908 Paris cedex 15, France. E-mail michel.azizi@egp.ap-hop-paris.fr
Key Words: angiotensin • renin • heart failure • hypertension • kidney
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
 |
Introduction |
|---|
Blockade of the renin-angiotensin system* (RAS) with ACE inhibitors or angiotensin II type 1 receptor (AT1R) antagonists has become one of the most successful therapeutic approaches in medicine. Within 25 years, substantial evidence has accumulated to indicate that this therapy reduces blood pressure (BP),1 left ventricular (LV) mass,2 and proteinuria.3 RAS blockade results in a decrease in cardiovascular morbidity and mortality in patients with chronic heart failure (CHF)4–6 or LV systolic dysfunction7 and after myocardial infarction (MI).8,9 RAS blockers retard the progression of renal insufficiency in type 1 (ACE inhibitors10) and type 2 (AT1R antagonists11,12) diabetes mellitus and nondiabetic chronic renal disease.13–15 Finally, a high dose of an ACE inhibitor administered in the evening reduces the rate of death, cardiac events, and stroke in patients with a high cardiovascular risk at baseline.16 Several mechanisms contribute to the beneficial effects of RAS blockers in cardiovascular and renal therapy, schematically the hemodynamic consequences of angiotensin II (Ang II) neutralization and the suppression of the Ang II–dependent generation of growth-promoting cytokines, free oxygen radicals, and fibrosis mediators in tissues.17
|
Concept of Combined RAS Blockade by ACE Inhibitors and AT1R Antagonists |
|---|
An ACE inhibitor administered at usual daily doses only suppresses plasma Ang II levels within a few hours after dose intake, and similarly, usual daily doses of an AT1R antagonist do not block AT1Rs over 24-hour periods.18,19 This has led to the concept of combined RAS blockade. The "escape" observed with single-site RAS blockers is due to the conjunction of the progressive clearance from the body of the drug at the end
This article has been cited by other articles:
 |
|
 |
|
  T. W. Doulton and G. A MacGregor Combination renin-angiotensin system blockade with the renin inhibitor aliskiren in hypertension Journal of Renin-Angiotensin-Aldosterone System, December 1, 2009; 10(4): 185 - 189. [Abstract] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 L. F. Fried, W. Duckworth, J. H. Zhang, T. O'Connor, M. Brophy, N. Emanuele, G. D. Huang, P. A. McCullough, P. M. Palevsky, S. Seliger, et al. Design of Combination Angiotensin Receptor Blocker and Angiotensin-Converting Enzyme Inhibitor for Treatment of Diabetic Nephropathy (VA NEPHRON-D) Clin. J. Am. Soc. Nephrol., February 1, 2009; 4(2): 361 - 368. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Imanishi, H. Tsujioka, H. Ikejima, A. Kuroi, S. Takarada, H. Kitabata, T. Tanimoto, Y. Muragaki, S. Mochizuki, M. Goto, et al. Renin Inhibitor Aliskiren Improves Impaired Nitric Oxide Bioavailability and Protects Against Atherosclerotic Changes Hypertension, September 1, 2008; 52(3): 563 - 572. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. M. Gutierrez, H. Tamez, I. Bhan, J. Zazra, M. Tonelli, M. Wolf, J. L. Januzzi, Y. Chang, and R. Thadhani N-terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) Concentrations in Hemodialysis Patients: Prognostic Value of Baseline and Follow-up Measurements Clin. Chem., August 1, 2008; 54(8): 1339 - 1348. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Segall, A. Covic, and D. J. A. Goldsmith Direct renin inhibitors: the dawn of a new era, or just a variation on a theme? Nephrol. Dial. Transplant., September 1, 2007; 22(9): 2435 - 2439. [Full Text] [PDF]
|
|
|
|
|
|
M. Azizi, J. Menard, A. Bissery, T.-T. Guyene, and A. Bura-Riviere Hormonal and Hemodynamic Effects of Aliskiren and Valsartan and Their Combination in Sodium-Replete Normotensive Individuals Clin. J. Am. Soc. Nephrol., September 1, 2007; 2(5): 947 - 955. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Waldmeier, U. Glaenzel, B. Wirz, L. Oberer, D. Schmid, M. Seiberling, J. Valencia, G.-J. Riviere, P. End, and S. Vaidyanathan Absorption, Distribution, Metabolism, and Elimination of the Direct Renin Inhibitor Aliskiren in Healthy Volunteers Drug Metab. Dispos., August 1, 2007; 35(8): 1418 - 1428. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. K. Koh, M. J. Quon, Y. Lee, S. H. Han, J. Y. Ahn, W.-J. Chung, J.-a Kim, and E. K. Shin Additive beneficial cardiovascular and metabolic effects of combination therapy with ramipril and candesartan in hypertensive patients Eur. Heart J., June 2, 2007; 28(12): 1440 - 1447. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. O'Brien, J. Barton, J. Nussberger, D. Mulcahy, C. Jensen, P. Dicker, and A. Stanton Aliskiren Reduces Blood Pressure and Suppresses Plasma Renin Activity in Combination With a Thiazide Diuretic, an Angiotensin-Converting Enzyme Inhibitor, or an Angiotensin Receptor Blocker Hypertension, February 1, 2007; 49(2): 276 - 284. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A.-I. Tropeano, P. Boutouyrie, B. Pannier, R. Joannides, E. Balkestein, S. Katsahian, B. Laloux, C. Thuillez, H. Struijker-Boudier, and S. Laurent Brachial Pressure-Independent Reduction in Carotid Stiffness After Long-Term Angiotensin-Converting Enzyme Inhibition in Diabetic Hypertensives Hypertension, July 1, 2006; 48(1): 80 - 86. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. B. Marrero, A. K. Banes-Berceli, D. M. Stern, and D. C. Eaton Role of the JAK/STAT signaling pathway in diabetic nephropathy Am J Physiol Renal Physiol, April 1, 2006; 290(4): F762 - F768. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. G. Tsouli, E. N. Liberopoulos, D. N. Kiortsis, D. P. Mikhailidis, and M. S. Elisaf Combined Treatment With Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers: A Review of the Current Evidence Journal of Cardiovascular Pharmacology and Therapeutics, March 1, 2006; 11(1): 1 - 15. [Abstract] [PDF]
|
|
|
|
|
|
D. N. Muller and F. C. Luft Direct Renin Inhibition with Aliskiren in Hypertension and Target Organ Damage Clin. J. Am. Soc. Nephrol., March 1, 2006; 1(2): 221 - 228. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M.A. van de Wal, D. J. van Veldhuisen, W. H. van Gilst, and A. A. Voors Addition of an angiotensin receptor blocker to full-dose ACE-inhibition: controversial or common sense? Eur. Heart J., November 2, 2005; 26(22): 2361 - 2367. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Baudin Polymorphism in angiotensin II receptor genes and hypertension Exp Physiol, May 1, 2005; 90(3): 277 - 282. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Azizi, J. Menard, A. Bissery, T.-T. Guyenne, A. Bura-Riviere, S. Vaidyanathan, and R. P. Camisasca Pharmacologic Demonstration of the Synergistic Effects of a Combination of the Renin Inhibitor Aliskiren and the AT1 Receptor Antagonist Valsartan on the Angiotensin II-Renin Feedback Interruption J. Am. Soc. Nephrol., December 1, 2004; 15(12): 3126 - 3133. [Abstract] [Full Text] [PDF]
|
|