Effects of statins in patients with chronic kidney disease: meta-analysis and meta-regression of randomised controlled trialsBMJ 2008; 336 doi: https://doi.org/10.1136/bmj.39472.580984.AE (Published 20 March 2008) Cite this as: BMJ 2008;336:645
- Giovanni F M Strippoli, editor of Cochrane Renal Group123,
- Sankar D Navaneethan, clinical fellow in nephrology4,
- David W Johnson, professor of nephrology5,
- Vlado Perkovic, associate director (clinical research)6,
- Fabio Pellegrini, biostatistician2,
- Antonio Nicolucci, head2,
- Jonathan C Craig, editor in chief of Cochrane Renal Group and associate professor of epidemiology13
- 1NHMRC Centre for Clinical Research Excellence in Renal Medicine, School of Public Health, University of Sydney, Australia
- 2Department of Clinical Pharmacology and Epidemiology, Mario Negri Sud Consortium, S Maria Imbaro (Ch), Italy
- 3Cochrane Renal Group, Sydney
- 4Division of Nephrology, University of Rochester, 601 Elmwood Avenue, Box 675, NY 14623, USA
- 5University of Queensland, Brisbane, Australia
- 6George Institute for International Health, Sydney
- Correspondence to: S D Navaneethan
- Accepted 11 January 2008
Objective To analyse the benefits and harms of statins in patients with chronic kidney disease (pre-dialysis, dialysis, and transplant populations).
Data sources Cochrane Central Register of Controlled Trials, Medline, Embase, and Renal Health Library (July 2006).
Study selection Randomised and quasi-randomised controlled trials of statins compared with placebo or other statins in chronic kidney disease.
Data extraction and analysis Two reviewers independently assessed trials for inclusion, extracted data, and assessed trial quality. Differences were resolved by consensus. Treatment effects were summarised as relative risks or weighted mean differences with 95% confidence intervals by using a random effects model.
Results Fifty trials (30 144 patients) were included. Compared with placebo, statins significantly reduced total cholesterol (42 studies, 6390 patients; weighted mean difference −42.28 mg/dl (1.10 mmol/l), 95% confidence interval −47.25 to −37.32), low density lipoprotein cholesterol (39 studies, 6216 patients; −43.12 mg/dl (1.12 mmol/l), −47.85 to −38.40), and proteinuria (g/24 hours) (6 trials, 311 patients; −0.73 g/24 hour, −0.95 to −0.52) but did not improve glomerular filtration rate (11 studies, 548 patients; 1.48 ml/min (0.02 ml/s), −2.32 to 5.28). Fatal cardiovascular events (43 studies, 23 266 patients; relative risk 0.81, 0.73 to 0.90) and non-fatal cardiovascular events (8 studies, 22 863 patients; 0.78, 0.73 to 0.84) were reduced with statins, but statins had no significant effect on all cause mortality (44 studies, 23 665 patients; 0.92, 0.82 to 1.03). Meta-regression analysis showed that treatment effects did not vary significantly with stage of chronic kidney disease. The side effect profile of statins was similar to that of placebo. Most of the available studies were small and of suboptimal quality; mortality data were provided by a few large trials only.
Conclusion Statins significantly reduce lipid concentrations and cardiovascular end points in patients with chronic kidney disease, irrespective of stage of disease, but no benefit on all cause mortality or the role of statins in primary prevention has been established. Reno-protective effects of statins are uncertain because of relatively sparse data and possible outcomes reporting bias.
We acknowledge the contribution of authors (C Wanner, C Baigent, H Holdaas, M Tonnelli, B G Stegmayr, R L Lins, M E Thomas, S H Diepeveen, A Zhang, M VanDijk, K P Harris, H Hernandez, D Saltissi, C Kosch, and T Nakamura) who provided data about their trials on request. We thank C Baigent and A Webster for their intellectual contribution to the manuscript. We also thank Catherine Clase and Martin Landray for critical review of this manuscript. We thank the Cochrane Renal Group staff and search coordinators for their assistance with the search process. This paper has been presented in part as an abstract at the Annual American Society of Nephrology meeting at St Louis, USA, in November 2004 and Philadelphia, USA, in November 2005.
Contributors: GFMS and SDN were equally involved in the concept and design of the review, data extraction, analysis and interpretation of data, and writing the final manuscript. FP was involved in data analysis. AN was involved in writing the final manuscript. DWJ was involved in analysis and interpretation of data and writing the final manuscript. VP was involved in critical revision for intellectual content and interpretation of data and assisted with writing the final manuscript. JCC was involved in concept and design, analysis and interpretation of data, and writing the final manuscript. All authors were involved in final approval of the manuscript to be submitted for publication. GFMS and SDN are the guarantors.
Funding: This review was supported in part by the Cochrane Renal Group.
Competing interests: None declared.
Ethical approval: Not needed.
Provenance and peer review: Not commissioned; externally peer reviewed.