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Meta-Analysis
. 2013 Sep 11;2013(9):CD004289.
doi: 10.1002/14651858.CD004289.pub5.

HMG CoA reductase inhibitors (statins) for dialysis patients

Suetonia C Palmer  1 , Sankar D Navaneethan, Jonathan C Craig, David W Johnson, Vlado Perkovic, Sagar U Nigwekar, Jorgen Hegbrant, Giovanni F M Strippoli
Affiliations
Meta-Analysis

HMG CoA reductase inhibitors (statins) for dialysis patients

Suetonia C Palmer et al. Cochrane Database Syst Rev. .

Abstract

Background: People with advanced kidney disease treated with dialysis experience mortality rates from cardiovascular disease that are substantially higher than for the general population. Studies that have assessed the benefits of statins (HMG CoA reductase inhibitors) report conflicting conclusions for people on dialysis and existing meta-analyses have not had sufficient power to determine whether the effects of statins vary with severity of kidney disease. Recently, additional data for the effects of statins in dialysis patients have become available. This is an update of a review first published in 2004 and last updated in 2009.

Objectives: To assess the benefits and harms of statin use in adults who require dialysis (haemodialysis or peritoneal dialysis).

Search methods: We searched the Cochrane Renal Group's Specialised Register to 29 February 2012 through contact with the Trials' Search Co-ordinator using search terms relevant to this review.

Selection criteria: Randomised controlled trials (RCTs) and quasi-RCTs that compared the effects of statins with placebo, no treatment, standard care or other statins on mortality, cardiovascular events and treatment-related toxicity in adults treated with dialysis were sought for inclusion.

Data collection and analysis: Two or more authors independently extracted data and assessed study risk of bias. Treatment effects were summarised using a random-effects model and subgroup analyses were conducted to explore sources of heterogeneity. Treatment effects were expressed as mean difference (MD) for continuous outcomes and risk ratios (RR) for dichotomous outcomes together with 95% confidence intervals (CI).

Main results: The risk of bias was high in many of the included studies. Random sequence generation and allocation concealment was reported in three (12%) and four studies (16%), respectively. Participants and personnel were blinded in 13 studies (52%), and outcome assessors were blinded in five studies (20%). Complete outcome reporting occurred in nine studies (36%). Adverse events were only reported in nine studies (36%); 11 studies (44%) reported industry funding.We included 25 studies (8289 participants) in this latest update; 23 studies (24 comparisons, 8166 participants) compared statins with placebo or no treatment, and two studies (123 participants) compared statins directly with one or more other statins. Statins had little or no effect on major cardiovascular events (4 studies, 7084 participants: RR 0.95, 95% CI 0.88 to 1.03), all-cause mortality (13 studies, 4705 participants: RR 0.96, 95% CI 0.90 to 1.02), cardiovascular mortality (13 studies, 4627 participants: RR 0.94, 95% CI 0.84 to 1.06) and myocardial infarction (3 studies, 4047 participants: RR 0.87, 95% CI 0.71 to 1.07); and uncertain effects on stroke (2 studies, 4018 participants: RR 1.29, 95% CI 0.96 to 1.72).Risks of adverse events from statin therapy were uncertain; these included effects on elevated creatine kinase (5 studies, 3067 participants: RR 1.25, 95% CI 0.55 to 2.83) or liver function enzymes (4 studies, 3044 participants; RR 1.09, 95% CI 0.41 to 1.25), withdrawal due to adverse events (9 studies, 1832 participants: RR 1.04, 95% CI 0.87 to 1.25) or cancer (2 studies, 4012 participants: RR 0.90, 95% CI 0.72 to 1.11). Statins reduced total serum cholesterol (14 studies, 1803 participants; MD -44.86 mg/dL, 95% CI -55.19 to -34.53) and low-density lipoprotein cholesterol (12 studies, 1747 participants: MD -39.99 mg/dL, 95% CI -52.46 to -27.52) levels. Data comparing statin therapy directly with another statin were sparse.

Authors' conclusions: Statins have little or no beneficial effects on mortality or cardiovascular events and uncertain adverse effects in adults treated with dialysis despite clinically relevant reductions in serum cholesterol levels.

PubMed Disclaimer

Conflict of interest statement

Vlado Perkovic is supported by a fellowship from the Heart Foundation of Australia and various grants from the Australian National Health and Medical Research Council. He has received speaker fees from Roche, Servier and Astra Zeneca, funding for a clinical trial from Baxter, and serves on Steering Committees for trials funded by Johnson and Johnson, Boehringer Ingelheim, Vitae and Abbott. His employer conducts clinical trials funded by Servier, Johnson and Johnson, Roche and Merck.

David Johnson is a consultant for Baxter Healthcare Pty Ltd and has previously received research funds from this company. He has also received speakers’ honoraria and research grants from Fresenius Medical Care and is a current recipient of a Queensland Government Health Research Fellowship. He has also received speakers' honoraria and consultancy fees from Amgen, Janssen‐Cilag, Shire, Lilley, Boehringer‐Ingelheim and Merck Sharpe & Dohme. He has received a research grant from Pfizer.

Suetonia Palmer received a fellowship administered by the Consorzio Mario Negri Sud from Amgen Dompe for assistance with travel for collaboration and supervision.

Figures

1
1
Study selection flow diagram
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study
1.1
1.1. Analysis
Comparison 1 Statin versus placebo or no treatment, Outcome 1 Major cardiovascular events.
1.2
1.2. Analysis
Comparison 1 Statin versus placebo or no treatment, Outcome 2 All‐cause mortality.
1.3
1.3. Analysis
Comparison 1 Statin versus placebo or no treatment, Outcome 3 Cardiovascular mortality.
1.4
1.4. Analysis
Comparison 1 Statin versus placebo or no treatment, Outcome 4 Fatal and non‐fatal myocardial infarction.
1.5
1.5. Analysis
Comparison 1 Statin versus placebo or no treatment, Outcome 5 Fatal and non‐fatal stroke.
1.6
1.6. Analysis
Comparison 1 Statin versus placebo or no treatment, Outcome 6 Elevated creatine kinase.
1.7
1.7. Analysis
Comparison 1 Statin versus placebo or no treatment, Outcome 7 Elevated liver function enzymes.
1.8
1.8. Analysis
Comparison 1 Statin versus placebo or no treatment, Outcome 8 Withdrawal due to adverse events.
1.9
1.9. Analysis
Comparison 1 Statin versus placebo or no treatment, Outcome 9 Cancer.
1.10
1.10. Analysis
Comparison 1 Statin versus placebo or no treatment, Outcome 10 Total cholesterol.
1.11
1.11. Analysis
Comparison 1 Statin versus placebo or no treatment, Outcome 11 LDL cholesterol.
1.12
1.12. Analysis
Comparison 1 Statin versus placebo or no treatment, Outcome 12 Triglycerides.
1.13
1.13. Analysis
Comparison 1 Statin versus placebo or no treatment, Outcome 13 HDL cholesterol.
2.1
2.1. Analysis
Comparison 2 Statin versus another statin, Outcome 1 Elevated liver function enzymes.
2.2
2.2. Analysis
Comparison 2 Statin versus another statin, Outcome 2 Withdrawal due to adverse events.
2.3
2.3. Analysis
Comparison 2 Statin versus another statin, Outcome 3 Total cholesterol.
2.4
2.4. Analysis
Comparison 2 Statin versus another statin, Outcome 4 LDL cholesterol.
2.5
2.5. Analysis
Comparison 2 Statin versus another statin, Outcome 5 Triglycerides.
2.6
2.6. Analysis
Comparison 2 Statin versus another statin, Outcome 6 HDL cholesterol.
See this image and copyright information in PMC

Comment in

References

References to studies included in this review

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Angel 2007 {published data only}
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Chang 2002 {published data only}
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Diepeveen 2005 {published data only}
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Dornbrook‐Lavender 2005 {published data only}
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Han 2011 {published data only}
    1. Han SH, Kang EW, Yoon SJ, Lee HC, Yoo TH, Choi KH, et al. Combined vascular effects of HMG‐CoA reductase inhibitor and angiotensin receptor blocker in non‐diabetic patients undergoing peritoneal dialysis. Nephrology Dialysis Transplantation 2011;26(11):3722‐8. [MEDLINE: ] - PubMed
Harris 2002 {published data only}
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Ichihara 2002 {published data only}
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Lins 2004 {published data only}
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PERFECT Study 1997 {published data only}
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    1. Walker RJ, Sutherland WH, Walker H. Simvastatin and cholesteryl ester transfer (CET) activity in renal failure (RF) [abstract]. ISN XIII International Congress of Nephrology; 1995 Jul 2‐6; Madrid (Spain). 1995:529.
Saltissi HD 2002 {published data only}
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Saltissi PD 2002 {published data only}
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SHARP Study 2010 {published data only}
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Soliemani 2011 {published data only}
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Stegmayr 2005 {published data only}
    1. Holmberg B, Brannstrom M, Bucht B, Crougneau V, Dimeny E, Ekspong A, et al. Safety and efficacy of atorvastatin in patients with severe renal dysfunction. Scandinavian Journal of Urology & Nephrology 2005;39(6):503‐10. [MEDLINE: ] - PubMed
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    1. Stegmayr BG, Brännström M, Bucht S, Crougneau V, Dimeny E, Ekspong A, et al. Low‐dose atorvastatin in severe chronic kidney disease patients: a randomized, controlled endpoint study. Scandinavian Journal of Urology & Nephrology 2005;39(6):489‐97. [MEDLINE: ] - PubMed
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Tse 2008 {published data only}
    1. Tse KC, Yung S, Tang CS, Tam S, Lai KN, Chan TM. Atorvastatin at conventional dose did not reduce C‐reactive protein in patients on peritoneal dialysis. Journal of Nephrology 2008;21(3):283. [MEDLINE: ] - PubMed
UK‐HARP‐I 2005 {published data only}
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van den Akker 2003 {published data only}
    1. Akker JM, Bredie SJ, Diepenveen SH, Tits LJ, Stalenhoef AF, Leusen R. Atorvastatin and simvastatin in patients on hemodialysis: effects on lipoproteins, C‐reactive protein and in vivo oxidized LDL. Journal of Nephrology 2003;16(2):238‐44. [MEDLINE: ] - PubMed
Vareesangthip 2005 {published data only}
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Velickovic 1997 {published data only}
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Vernaglione 2003 {published data only}
    1. Vernaglione L, Cristofano C, Muscogiuri P, Chimienti S. Does atorvastatin influence serum C‐reactive protein levels in patients on long‐term hemodialysis?. American Journal of Kidney Diseases 2004;43(3):471‐8. [MEDLINE: ] - PubMed
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Yu 2007 {published data only}
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References to studies excluded from this review

Akcicek 1996 {published data only}
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Bunio 2004 {published data only}
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Cappelli 2000 {published data only}
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Cheng 1995 {published data only}
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CHORUS Study 2001 {published data only}
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Dogra 2007 {published data only}
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Fiorini 1992 {published data only}
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Fiorini 1994 {published data only}
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Hufnagel 2000 {published data only}
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References to ongoing studies

Nardi 2005 {published data only}
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NCT00858637 {published data only}
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