Dual blockade of the renin-angiotensin-aldosterone system: beyond the ACE inhibitor and angiotensin-II receptor blocker combination.
The renin-angiotensin-aldosterone system (RAAS), an important regulator of blood pressure as well as fluid and electrolyte balance, plays an important role in the pathophysiology of cardiovascular and kidney diseases. Blockade of the RAAS with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-II (ANG-II) receptor blockers (ARBs) lowers blood pressure, decreases morbidity and mortality in patients with chronic heart failure, and decreases proteinuria and the rate of decline in renal function in patients with chronic kidney disease. Although these drugs are highly effective and are widely used in the management of cardiovascular and kidney diseases, current treatment regimens with ACEIs and ARBs may not completely suppress the RAAS. Combinations of ACEIs and ARBs have been shown to be superior to either agent alone for some, but certainly not all, composite cardiovascular and kidney outcomes. With the growing appreciation of the role of aldosterone in the pathogenesis of cardiorenal diseases and the recent approval of the direct renin inhibitor (DRI), aliskiren, additional combination strategies have emerged that may offer novel ways to more fully suppress the RAAS. This review examines what is presently known about ACEI/ARB combination therapy and explores alternative combination strategies that include DRIs and mineralocorticoid receptor blockers (MRBs).
Bomback
Andrew S
AS
Department of Medicine, Division of Nephrology, Columbia University College of Physicians and Surgeons, New York, New York, USA. asb68@columbia.edu
Toto
Robert
R
D000450:Aldosterone / Q000378:metabolism; D000577:Amides / Q000627:therapeutic use; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005650:Fumarates / Q000627:therapeutic use; D006801:Humans; D007674:Kidney Diseases / Q000188:drug therapy; D018161:Receptors, Mineralocorticoid / Q000819:agonists; D012084:Renin-Angiotensin System / Q000187:drug effects*
D000577:Amides; D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D005650:Fumarates; D018161:Receptors, Mineralocorticoid; D000450:Aldosterone; C446481:aliskiren