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Inhibition of the reninangiotensinaldosterone system: is there room for dual blockade in the cardiorenal continuum?

Volpe, Massimoa,b; Danser, A.H. Janc; Menard, Joëld,e,f; Waeber, Bernardg; Mueller, Dominik N.h,i; Maggioni, Aldo P.j; Ruilope, Luis M.k

Journal of Hypertension:
doi: 10.1097/HJH.0b013e32834f6e00

Antagonism of renin–angiotensin–aldosterone system is exerted through angiotensin-converting enzyme inhibitors, angiotensin receptor antagonists, renin inhibitors and mineralocorticoid receptor antagonists. These drugs have been successfully tested in numerous trials and in different clinical settings. The original indications of renin–angiotensin–aldosterone system blockers have progressively expanded from the advanced stages to the earlier stages of cardiorenal continuum. To optimize the degree of blockade of renin–angiotensin–aldosterone system, dose uptitrations of angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists or the use of a dual blockade, initially identified with the combination of angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists, have been proposed. The data from the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) study do not support this specific dual blockade approach. However, the dual blockade of angiotensin-converting enzyme inhibitors/angiotensin receptor antagonists with direct renin inhibitors is currently under investigation while that based on an aldosterone blocker with any of the previous three drugs requires more evidence beyond heart failure. In this review, we revisited potential advantages of dual blockade of renin–angiotensin–aldosterone system in arterial hypertension and diabetes.

Author Information

aDivision of Cardiology, Department of Clinical and Molecular Medicine, Faculty of Medicine, University of Rome ‘La Sapienza’, Rome

bIRCCS Neuromed, Pozzilli, Italy

cDivision of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands

dFaculté de Médecine, Universitè Paris Descartes

eAssistanca Publique des Hopitaux de Paris, Hopital Européen Georges Pompidou

fINSERM, Paris, France

gDivision of Clinical Pathophysiology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland

hMax-Delbruck Center

iExperimental and Clinical Research Center, Berlin, Germany

jANMCO Research Center, Firenze, Italy

kUnidad de Hipertension, Hospital 12 de Octubre, Madrid, Spain

Correspondence to Professor Massimo Volpe, Chair and Division of Cardiology, Department of Clinical and Molecular Medicine, Faculty of Medicine, Sant’Andrea Hospital, University of Rome ‘La Sapienza’, Via di Grottarossa 1035-9, 00189 Rome, Italy. Tel: +39 06 3377 5654; fax +39 06 3377 5061; e-mail:

Abbreviations: ACEi, angiotensin-converting enzyme inhibitor; ARB, type 1 angiotensin II receptor blocker; BP, blood pressure; DRI, direct renin inhibitor; LIFE, Losartan Intervention For Endpoint reduction; LVH, left ventricular hypertrophy; MAU, microalbuminuria; ONTARGET, Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial; RAAS, renin–angiotensin–aldosterone system; ROADMAP, Randomised Olmesartan and Diabetes Micro-albuminuria Prevention

Received 28 September, 2011

Revised 10 November, 2011

Accepted 18 November, 2011

© 2012 Lippincott Williams & Wilkins, Inc.