[en] The blockade of the renin-angiotensin-aldosterone system (RAAS) is helpful in the management of arterial hypertension, congestive heart failure, post-myocardial infarction and diabetic nephropathy. Such blockade can be obtained with an angiotensin converting enzyme inhibitor, a specific antagonist of angiotensin II AT1 receptors, an aldosterone receptor antagonist and/or a direct inhibitor of renin such as aliskiren. Various studies have demonstrated that a dual or even triple RAAS inhibition may offer a better cardiorenal protection, in refractory congestive heart failure and in nephropathy with proteinuria. However, in the ONTARGET study, the dual inhibition with ramipril plus telmisartan did not provide any additional benefit compared to ramipril alone in high-risk cardiovascular patients, but showed a worse tolerance profile.
Legrand, Delphine ; Centre Hospitalier Universitaire de Liège - CHU > Frais communs médecine
Krzesinski, Jean-Marie ; Université de Liège - ULiège > Département des sciences cliniques > Néphrologie
Scheen, André ; Université de Liège - ULiège > Département des sciences cliniques > Diabétologie, nutrition et maladie métaboliques - Médecine interne générale
Language :
French
Title :
Quelle place pour une double ou triple inhibition du systeme renine-angiotensine-aldosterone ?
Alternative titles :
[fr] What is the purpose of dual or triple inhibition of the renin-angiotensin-aldosterone system?
Stojiljkovic L, Behnia R. Role of renin angiotensin system inhibitors in cardiovascular and renal protection : A lesson from clinical trials. Curr Pharm Des 2007;13:1335-45.
Cohn JN. Reducing cardiovascular risk by blockade of the renin-angiotensin-aldosterone system. Adv Ther 2007;24:1290-304.
White WB. Angiotensin-converting enzyme inhibitors in the treatment of hypertension : An update. J Clin Hypertens 2007;9:876-82.
Jorde UP. Suppression of the renin-angiotensin-aldosterone system in chronic heart failure : Choice of agents and clinical impact. Cardiol Rev 2006;14:81-7.
* Schmieder RE, Hilgers KF, Schlaich MP, Schmidt BM. Renin-angiotensin system and cardiovascular risk. Lancet 2007;369:1208-19.
Gurley SB, Coffman TM. The renin-angiotensin system and diabetic nephropathy. Semin Nephrol 2007;27:144-52.
* Balamuthusamy S, Srinivasan L, Verma M, et al. Renin angiotensin system blockade and cardiovascular outcomes in patients with chronic kidney disease and proteinura : A meta-analysis. Am Heart J 2008;155:791-805.
Scheen AJ. Renin-angiotensin system inhibition prevents type 2 diabetes mellitus. Part I. A meta-analysis of randomised clinical trials. Diabetes Metab 2004;30:487-96.
Thomas GN, Tomlinson B. Prevention of macrovascular disease in type 2 diabetic patients : Blockade of the renin-angiotensin-aldosterone system. Curr Diabetes Rev 2008;4:63-78.
* Weir MR. Effects of renin-angiotensin system inhibition on end-organ protection : Can we do better? Clin Ther 2007;29:1803-24.
Werner C, Baumhäkel M, Teo KK, et al. RAS blockade with ARB and ACE inhibitors : Current perspective on rationale and patient selection. Clin Res Cardiol 2008;97:418-31.
Schleich F, Krzesinski JM, Piérard L, Scheen AJ. Comment je traite. . . en optimisant le blocage du système rénine- angiotensine-aldostérone. Rev Med Liège 2008;63:174-81.
Blumenfeld JD, Sealey JE, Mann SJ, et al. Beta-adrenergic receptor blockade as a therapeutic approach for suppressing the renin-angiotensin- aldosterone system in normotensive and hypertensive subjects. Am J Hypertens 1999;12:451-9.
Struthers AD. Aldosterone blockade in cardiovascular disease. Heart 2004;90:1229-34.
* Sato A, Saruta T, Funder JW. Combination therapy with aldosterone blockade and renin-angiotensin inhibitors confers organ protection. Hypertens Res 2006;29:211-6.
Dendorfer A, Dominiak P, Schunkert H. ACE inhibitors and angiotensin II receptor antagonists. Handb Exp Pharmacol 2005;170:407-42.
Burnier M, Brunner HR. Angiotensin II receptor antagonists. Lancet 2000;355:637-45.
Gradman AH, Kad R. Renin inhibition in hypertension. J Am Coll Cardiol 2008;51:519-28.
Shafiq MM, Menon DV, Victor RG. Oral direct renin inhibition : Premise, promise, and potential limitations of a new antihypertensive drug. Am J Med 2008;121:265-71.
Doulton TW, He FJ, MacGregor GA. Systematic review of combined angiotensin-converting enzyme inhibition and angiotensin receptor blockade in hypertension. Hypertension 2005;45:880-6.
Weber MA. New opportunities in cardiovascular patient management : A survey of clinical data on the combination of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Am J Cardiol 2007;100(3A):45J-52.
* Azizi M, Wuerzner G. Rationale for combining blockers of the renin-angiotensin system. Semin Nephrol 2007;27:544-54.
Cohn JN, Goldman JM. Establishing a new option for target-organ protection : Rationale for ARB plus ACE inhibitor combination therapy. Am J Hypertens 2008;21:248-56.
Bakris GL, Weir MR. Comparison of dual RAAS blockade and higher-dose RAAS inhibition on nephropathy progression. Postgrad Med 2008;120:33-42.
* The ONTARGET Investigators. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med 2008;358:1547-59.
Carey RM, Siragy HM. Newly recognized components of the renin-angiotensin system : Potential roles in cardiovascular and renal regulation. Endocr Rev 2003;24:261-71.
Atlas SA. The renin-angiotensin aldosterone system : Pathophysiological role and pharmacologic inhibition. J Manag Care Pharm 2007;13(Suppl. S-b):S9-20.
Bakris GL, Ruilope L, Locatelli F, et al. Treatment of microalbuminuria in hypertensive subjects with elevated cardiovascular risk : Results of the IMPROVE trial. Kidney Int 2007;72:879-85.
Nakao N, Yoshimura A, Morita H, et al. Combination treatment of angiotensin-II receptor blocker and angiotensin-converting- enzyme inihibitor in non-diabetic renal disease (COOPERATE) : A randomised controlled trial. Lancet 2003;361:117-24.
* McMurray JJ, Ostergren J, Swedberg K, et al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors : The CHARM-Added trial. Lancet 2003;362:767-71.
Cohn JN, Tognoni G; Valsartan Heart failure trial investigators. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med 2001;345:1667-75.
Pfeffer MA, McMurray JJ, Velazquez EJ, et al. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med 2003;349:1893-906.
Waeber B. Le renouveau des antagonistes de l'aldostérone. Rev Med Suisse 2006;2:2055-8.
Pitt B, Zannad F, Remme WJ, et al for the Randomized aldactone evaluation study investigators. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med 1999;341:709-17.
Pitt B, Remme W, Zannad F, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003;348:1309-21.
McManus F, McInnes GT, Connell JMC. Drug insight : Eplerenone, a mineralocorticoid-receptor antagonist. Nat Clin Pract Endocrinol Metab 2008;4:44-52.
Shah NC, Pringle S, Struthers A. Aldosterone blockade over and above ACE-inhibitors in patients with coronary artery disease but without heart failure. J Renin Angiotensin Aldosterone Syst 2006;7:20-30.
* Staessen JA, Li Y, Richart T. Oral renin inhibitors. Lancet 2006;368:1449-56.
Frampton JE, Curran MP. Aliskiren. A review of its use in the management of hypertension. Drugs 2007;67:1767-92.
Parving HH, Persson F, Lewis JB, Lewis EJ, Hollenberg NK, for the AVOID study investigators. Aliskiren combined with losartan in type 2 diabetes and nephropathy. N Engl J Med 2008;358:2433-46.
Chrysant SG, Murray AV, Hoppe UC, et al. Long-term safety, tolerability and efficacy of aliskiren in combination with valsartan in patients with hypertension : A 6-month interim analysis. Curr Med Res Opin 2008;24:1039-47.
Cravedi P, Ruggenenti P Remuzi G. Intensified inhibition of renin-angiotensin system : A way to improve renal protection ? Curr Hypertens Rep 2007;9:430-6.
Jneid H, Moukarbel GV, Dawson B, Hajjar RJ, Francis GS. Combining neuroendocrine inhibitors in heart failure : Reflections on safety and efficacy. Am J Med 2007;120:1090.e1-8.
Tylicki L, Rutkowski P, Renke M, et al. Triple pharmacological blockade of the renin-angiotensin-aldosterone system in nondiabettc CKD : An open-label crossover randomized controlled trial. Am J Kidney Dis 2008 Apr 17. Epub ahead of print.
Furumatsu Y, Nagasawa Y, Tomida K, et al. Effect of renin-angiotensin- aldosterone system triple blockade on non-diabetic renal disease : Addition of an aldosterone blocker, spironolactone, to combination treatment with an angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker. Hypertens Res 2008;31:59-67.
Weir RA, McMurray JJ, Puu M, et al. Efficacy and tolerability of adding an angiotensin receptor blocker in patients with heart failure already receiving an angiotensin-converting inhibitor plus aldosterone antagonist, with or without a beta blocker. Findings from the candesartan in heart failure : Assessment of reduction in mortality and morbidity (CHARM)-Added trial. Eur J Heart Fail 2008;10:157-63.
