REVIEWSInhibition of the renin–angiotensin–aldosterone 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 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: [email protected] 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 Journal of Hypertension: April 2012 - Volume 30 - Issue 4 - p 647-654 doi: 10.1097/HJH.0b013e32834f6e00 Buy Metrics Abstract 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. © 2012 Lippincott Williams & Wilkins, Inc.