Renal and cardio-protective effects of direct renin inhibition: a systematic literature review : Journal of Hypertension

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Meta-analyses

Renal and cardio-protective effects of direct renin inhibition: a systematic literature review

Lambers Heerspink, Hiddo Ja,b; Perkovic, Vladob; de Zeeuw, Dicka

Author Information

aDepartment of Clinical Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

bGeorge Institute for International Health, University of Sydney, Sydney, Australia

Received 21 April, 2009

Revised 6 July, 2009

Accepted 21 July, 2009

Correspondence to Dick de Zeeuw, MD, PhD, Professor and Head, Department of Clinical Pharmacology, University Medical Center Groningen, Sector F, PO Box 196, 9700 AD Groningen, The Netherlands Tel: +31 50 3632810; fax: +31 50 3632812; e-mail: [email protected]

Journal of Hypertension 27(12):p 2321-2331, December 2009. | DOI: 10.1097/HJH.0b013e3283310f92

Abstract

Background 

Blockade of the renin–angiotensin–aldosterone system (RAAS) at its rate-limiting step by means of renin inhibition has led to the development of direct renin inhibitors (DRIs). Given the renal and cardioprotective effects of RAAS blockade by angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers, DRIs may increase the armamentarium for further organ protection. Over the last two decades the effects of DRIs on biomarkers for renal and cardiovascular disease have been investigated. This systematic review aims to delineate the effects of DRIs on surrogate markers of renal and cardiovascular function.

Methods 

MEDLINE and previous systematic reviews were searched for articles reported between 1980 and 2008. A standardized dataset was extracted from articles describing the effects of DRIs on markers of renal and cardiac damage and hard outcomes.

Results 

Fifty-two articles were included. Blood pressure reductions were generally insufficient using early generation DRIs. However, recent DRIs have greater blood pressure-lowering effects. Preclinical and clinical studies showed profound effects of DRIs on markers of renal function, including clear increases in renal plasma flow and reductions in albuminuria. These effects were observed either alone or in combination with other RAAS inhibitors and suggest potential large renal protective benefit. DRIs improved hemodynamic cardiovascular parameters, such as total peripheral resistance, arterial pressure and left ventricular mass index, to a similar extent as those observed with other RAAS inhibitors. Furthermore, addition of DRIs to optimal heart failure treatment resulted in further reductions in B-type natriuretic peptide.

Conclusions 

Evidence from preclinical and clinical studies suggests that DRIs may have renal and cardiovascular effects beyond their ability to lower blood pressure. Results of ongoing hard outcome trials are awaited to definitively assess the renal and cardio-protective effects of these agents.

© 2009 Lippincott Williams & Wilkins, Inc.

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