Angiotensin converting enzyme inhibitors and angiotensin

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  • 1.Angiotensin-converting enzyme inhibitors and angiotensinreceptor blockers for adults with early (stage 1 to 3) non-diabetic chronic kidney disease (Review)Sharma P, Blackburn RC, Parke CL, McCullough K, Marks A, Black CThis is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library2011, Issue 10http://www.thecochranelibrary.comAngiotensin-converting enzyme inhibitors and angiotensin receptor blockers for adults with early (stage 1 to 3) non-diabetic chronickidney disease (Review)Copyright 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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T A B L E O F C O N T E N T S1HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2SUMMARY OF FINDINGS FOR THE MAIN COMPARISON . . . . . . . . . . . . . . . . . . .5BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .6OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .6METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Figure 1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10Figure 2. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12Figure 3. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1316ADDITIONAL SUMMARY OF FINDINGS . . . . . . . . . . . . . . . . . . . . . . . . . .18DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .19AUTHORS CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .20ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .20REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .29CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . .43DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Analysis 1.1. Comparison 1 ACEi versus placebo, Outcome 1 Mortality. . . . . . . . . . . . . . . . . 44Analysis 1.2. Comparison 1 ACEi versus placebo, Outcome 2 Cardiovascular events. . . . . . . . . . . . 45Analysis 1.3. Comparison 1 ACEi versus placebo, Outcome 3 Doubling of creatinine. . . . . . . . . . . . 46Analysis 1.4. Comparison 1 ACEi versus placebo, Outcome 4 Doubling of creatinine by underlying renal pathologies. 47Analysis 1.5. Comparison 1 ACEi versus placebo, Outcome 5 Adverse events. . . . . . . . . . . . . . . 4848ADDITIONAL TABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .49APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .54CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . .54DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .55SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .55DIFFERENCES BETWEEN PROTOCOL AND REVIEW . . . . . . . . . . . . . . . . . . . . .55INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .iAngiotensin-converting enzyme inhibitors and angiotensin receptor blockers for adults with early (stage 1 to 3) non-diabetic chronickidney disease (Review)Copyright 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 3. [Intervention Review]Angiotensin-converting enzyme inhibitors and angiotensinreceptor blockers for adults with early (stage 1 to 3) non-diabetic chronic kidney diseasePawana Sharma1, Rachel C Blackburn2, Claire L Parke2, Keith McCullough2, Angharad Marks2, Corri Black21Health Services Research Unit, University of Aberdeen, Aberdeen, UK. 2Institute of Applied Health Sciences, University of Aberdeen,Aberdeen, UKContact address: Corri Black, Institute of Applied Health Sciences, University of Aberdeen, Foresterhill, Aberdeen, Grampian, AB526NZ, UK. corri.black@abdn.ac.uk.Editorial group: Cochrane Renal Group.Publication status and date: New, published in Issue 10, 2011.Review content assessed as up-to-date: 7 March 2010.Citation: Sharma P, Blackburn RC, Parke CL, McCullough K, Marks A, Black C. Angiotensin-converting enzyme inhibitors andangiotensin receptor blockers for adults with early (stage 1 to 3) non-diabetic chronic kidney disease. Cochrane Database of SystematicReviews 2011, Issue 10. Art. No.: CD007751. DOI: 10.1002/14651858.CD007751.pub2.Copyright 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.A B S T R A C TBackgroundChronic kidney disease (CKD) is a long term condition that occurs as a result of damage to the kidneys. Early recognition of CKDis becoming increasingly common due to widespread laboratory estimated glomerular ltration rate (eGFR) reporting, raised clinicalawareness, and international adoption of Kidney Disease Outcomes Quality Initiative (K/DOQI) classication. Early recognition andmanagement of CKD affords the opportunity not only to prepare for progressive kidney impairment and impending renal replacementtherapy, but also for intervening to reduce the risk of progression and cardiovascular disease. Angiotensin-converting enzyme inhibitors(ACEi) and angiotensin receptor blockers (ARB) are two classes of antihypertensive drugs that act on the renin-angiotensin-aldosteronesystem. Benecial effects of ACEi and ARB on renal outcomes and survival in people with a wide range of severity of renal impairmenthave been reported; however, their effectiveness in the subgroup of people with early CKD (stage 1 to 3) is less certain.ObjectivesThis review aimed to evaluate the benets and harms of ACEi and ARB or both in the management of people with early (stage 1 to 3)CKD who do not have diabetes mellitus.Search methodsIn March 2010 we searched The Cochrane Library, including The Cochrane Renal Groups specialised register and The CochraneCentral Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE. Reference lists of review articles and relevant studieswere also checked. The search was conducted using the optimally sensitive strategy developed by the Cochrane Collaboration for theidentication of randomised controlled trials (RCTs) with input from an expert in trial search strategy.Selection criteriaAll RCTs reporting the effect of ACEi or ARB in people with early (stage 1 to 3) CKD who did not have diabetes mellitus were selectedfor inclusion. Only studies of at least four weeks duration were selected. Authors, working in teams of two, independently assessed theretrieved titles and abstracts, and whenever necessary the full text of these studies were screened to determine which studies satisedthe inclusion criteria.1Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers for adults with early (stage 1 to 3) non-diabetic chronickidney disease (Review)Copyright 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 4. Data collection and analysisData extraction was carried out by two authors, independently, using a standard data extraction form and cross checked by two otherauthors. Methodological quality of included studies was assessed using the Cochrane risk of bias tool. Data entry was carried out by oneauthor and cross checked by another author. When more than one study reported similar outcomes, data were pooled using the random-effects model, but a xed-effect model was also analysed to ensure the robustness of the model chosen and to check susceptibility tooutliers. Heterogeneity was analysed using a Chi test on N-1 degrees of freedom, with an alpha of 0.05 used for statistical signicanceand with the I test. Where data permitted, subgroup analysis was used to explore possible sources of heterogeneity. The quality of theevidence was analysed.Main resultsFour RCTs enrolling 2177 participants met our inclusion criteria. Of these, three compared ACEi with placebo and one comparedACEi with ARB. Two studies had an overall low risk of bias, and the other two were considered to be at moderate to high risk of bias.Low to moderate quality of evidence (from two studies representing 1906 patients) suggested that ACEi had no impact on all-causemortality (RR 1.80, 95% CI 0.17 to 19.27, P = 0.63) or cardiovascular events (RR 0.87, 95% CI 0.66 to 1.14, P = 0.31) in peoplewith stage 3 CKD. For all-cause mortality, there was substantial heterogeneity in the results. One study (quality assessment: low riskof bias) reported no difference in the risk of end-stage kidney disease in those with an eGFR > 45 mL/min/1.74 m treated with ACEiversus placebo (RR 1.00, 95% CI 0.09 to 1.11, P = 0.99). The (high risk of bias) study that compared ACEi with ARB reported littledifference in effect between the treatments when urinary protein, blood pressure or creatinine clearance were compared. No publishedstudies comparing ARB with placebo or ACEi and ARB with placebo were identied.Authors conclusionsOur review demonstrated that there is currently insufcient evidence to determine the effectiveness of ACEi or ARB in patients withstage 1 to 3 CKD who do not have diabetes mellitus. We have identied an area of signicant uncertainty for a group of patients whoaccount for most of those labelled as having CKD.P L A I N L A N G U A G E S U M M A R YAngiotensin-converting enzyme inhibitors and angiotensin receptor blockers for adults with early chronic kidney disease whodo not have diabetesChronic kidney disease (CKD) is a long-term condition that occurs as a result of the kidneys being damaged. Progressive deteriorationof kidney function can lead to end-stage kidney disease (ESKD). People with ESKD cannot maintain healthy kidney function andneed kidney dialysis or transplant. In the early stages of CKD, patients may not have any outward sympt