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Effect of inhibitors of the renin-angiotensin system and other antihypertensive drugs on renal outcomes: systematic review and meta-analysis.
Lancet. 2005 Dec 10; 366(9502):2026-33.Lct

Abstract

BACKGROUND

A consensus has emerged that angiotensin-converting-enzyme (ACE) inhibitors and angiotensin-II receptor blockers (ARBs) have specific renoprotective effects. Guidelines specify that these are the drugs of choice for the treatment of hypertension in patients with renal disease. We sought to determine to what extent this consensus is supported by the available evidence.

METHODS

Electronic databases were searched up to January, 2005, for randomised trials assessing antihypertensive drugs and progression of renal disease. Effects on primary discrete endpoints (doubling of creatinine and end-stage renal disease) and secondary continuous markers of renal outcomes (creatinine, albuminuria, and glomerular filtration rate) were calculated with random-effect models. The effects of ACE inhibitors or ARBs in placebo-controlled trials were compared with the effects seen in trials that used an active comparator drug.

FINDINGS

Comparisons of ACE inhibitors or ARBs with other antihypertensive drugs yielded a relative risk of 0.71 (95% CI 0.49-1.04) for doubling of creatinine and a small benefit on end-stage renal disease (relative risk 0.87, 0.75-0.99). Analyses of the results by study size showed a smaller benefit in large studies. In patients with diabetic nephropathy, no benefit was seen in comparative trials of ACE inhibitors or ARBs on the doubling of creatinine (1.09, 0.55-2.15), end-stage renal disease (0.89, 0.74-1.07), glomerular filtration rate, or creatinine amounts. Placebo-controlled trials of ACE inhibitors or ARBs showed greater benefits than comparative trials on all renal outcomes, but were accompanied by substantial reductions in blood pressure in favour of ACE inhibitors or ARBs.

INTERPRETATION

The benefits of ACE inhibitors or ARBs on renal outcomes in placebo-controlled trials probably result from a blood-pressure-lowering effect. In patients with diabetes, additional renoprotective actions of these substances beyond lowering blood pressure remain unproven, and there is uncertainty about the greater renoprotection seen in non-diabetic renal disease.

Authors+Show Affiliations

Centre for Clinical Pharmacology, Department of Medicine, BHF laboratories at University College London, London, UK. juan.pablo-casas@lshtm.ac.ukNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
Review
Systematic Review

Language

eng

PubMed ID

16338452

Citation

Casas, Juan P., et al. "Effect of Inhibitors of the Renin-angiotensin System and Other Antihypertensive Drugs On Renal Outcomes: Systematic Review and Meta-analysis." Lancet (London, England), vol. 366, no. 9502, 2005, pp. 2026-33.
Casas JP, Chua W, Loukogeorgakis S, et al. Effect of inhibitors of the renin-angiotensin system and other antihypertensive drugs on renal outcomes: systematic review and meta-analysis. Lancet. 2005;366(9502):2026-33.
Casas, J. P., Chua, W., Loukogeorgakis, S., Vallance, P., Smeeth, L., Hingorani, A. D., & MacAllister, R. J. (2005). Effect of inhibitors of the renin-angiotensin system and other antihypertensive drugs on renal outcomes: systematic review and meta-analysis. Lancet (London, England), 366(9502), 2026-33.
Casas JP, et al. Effect of Inhibitors of the Renin-angiotensin System and Other Antihypertensive Drugs On Renal Outcomes: Systematic Review and Meta-analysis. Lancet. 2005 Dec 10;366(9502):2026-33. PubMed PMID: 16338452.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of inhibitors of the renin-angiotensin system and other antihypertensive drugs on renal outcomes: systematic review and meta-analysis. AU - Casas,Juan P, AU - Chua,Weiliang, AU - Loukogeorgakis,Stavros, AU - Vallance,Patrick, AU - Smeeth,Liam, AU - Hingorani,Aroon D, AU - MacAllister,Raymond J, PY - 2005/12/13/pubmed PY - 2006/1/4/medline PY - 2005/12/13/entrez SP - 2026 EP - 33 JF - Lancet (London, England) JO - Lancet VL - 366 IS - 9502 N2 - BACKGROUND: A consensus has emerged that angiotensin-converting-enzyme (ACE) inhibitors and angiotensin-II receptor blockers (ARBs) have specific renoprotective effects. Guidelines specify that these are the drugs of choice for the treatment of hypertension in patients with renal disease. We sought to determine to what extent this consensus is supported by the available evidence. METHODS: Electronic databases were searched up to January, 2005, for randomised trials assessing antihypertensive drugs and progression of renal disease. Effects on primary discrete endpoints (doubling of creatinine and end-stage renal disease) and secondary continuous markers of renal outcomes (creatinine, albuminuria, and glomerular filtration rate) were calculated with random-effect models. The effects of ACE inhibitors or ARBs in placebo-controlled trials were compared with the effects seen in trials that used an active comparator drug. FINDINGS: Comparisons of ACE inhibitors or ARBs with other antihypertensive drugs yielded a relative risk of 0.71 (95% CI 0.49-1.04) for doubling of creatinine and a small benefit on end-stage renal disease (relative risk 0.87, 0.75-0.99). Analyses of the results by study size showed a smaller benefit in large studies. In patients with diabetic nephropathy, no benefit was seen in comparative trials of ACE inhibitors or ARBs on the doubling of creatinine (1.09, 0.55-2.15), end-stage renal disease (0.89, 0.74-1.07), glomerular filtration rate, or creatinine amounts. Placebo-controlled trials of ACE inhibitors or ARBs showed greater benefits than comparative trials on all renal outcomes, but were accompanied by substantial reductions in blood pressure in favour of ACE inhibitors or ARBs. INTERPRETATION: The benefits of ACE inhibitors or ARBs on renal outcomes in placebo-controlled trials probably result from a blood-pressure-lowering effect. In patients with diabetes, additional renoprotective actions of these substances beyond lowering blood pressure remain unproven, and there is uncertainty about the greater renoprotection seen in non-diabetic renal disease. SN - 1474-547X UR - https://www.unboundmedicine.com/medline/citation/16338452/Effect_of_inhibitors_of_the_renin_angiotensin_system_and_other_antihypertensive_drugs_on_renal_outcomes:_systematic_review_and_meta_analysis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0140-6736(05)67814-2 DB - PRIME DP - Unbound Medicine ER -