Inhibition of the renin-angiotensin-aldosterone system: is there room for dual blockade in the cardiorenal continuum?

• Published in: Journal of hypertension Vol. 30; no. 4; p. 647
• Main Authors: Volpe, Massimo, Danser, A H Jan, Menard, Joël, Waeber, Bernard, Mueller, Dominik N, Maggioni, Aldo P, Ruilope, Luis M
• Format: Journal Article
• Language: English
• Published: England 01.04.2012
• Subjects: Angiotensin II Type 1 Receptor Blockers - therapeutic use; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Antihypertensive Agents - therapeutic use; Benzimidazoles - therapeutic use; Benzoates - therapeutic use; Diabetes Complications - drug therapy; Diabetes Mellitus - drug therapy; Dose-Response Relationship, Drug; Drug Therapy, Combination; Humans; Hypertension - drug therapy; Hypertension - etiology; Mineralocorticoid Receptor Antagonists; Ramipril - therapeutic use; Renin - antagonists & inhibitors; Renin-Angiotensin System - drug effects
• ISSN: 1473-5598
• 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.