title: Reducing cardiorenal risk through combination therapy with a direct renin inhibitor.
abstract: Interruption of the renin-angiotensin-aldosterone system (RAAS) cascade with angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or more recently direct renin inhibitors (DRIs) is a safe and effective antihypertensive strategy that is in routine clinical use. The clinical utility of these agents in cardiorenal end-organ protection is increasingly being recognized. Although both ACE inhibitors and ARBs demonstrate substantial benefit in patients with cardiovascular and/or renal disease, considerable evidence indicates that they only partially suppress the RAAS pathway due to feedback upregulation of plasma renin activity. With the goal of providing more comprehensive RAAS blockade, combination ACE inhibitor/ARB therapy has been evaluated. However, this approach has not shown the anticipated improvements in composite cardiovascular and renal outcomes and appears to be associated with significant toxicity. Due to a unique mechanism of action, the combination of a DRI with an ACE inhibitor or ARB may represent an effective end-organ-protective therapeutic strategy.
authors: David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA. arastogi@mednet.ucla.edu
authors: Anjay
authors: A
authors: Rastogi
authors: Mohamad
authors: M
authors: Rashid
authors: Richard F
authors: RF
authors: Wright
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000517:prevention & control; D004359:Drug Therapy, Combination; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007674:Kidney Diseases / Q000517:prevention & control; D012084:Renin-Angiotensin System / Q000187:drug effects; D000092502:Renin Inhibitors
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000092502:Renin Inhibitors