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Benefits and Harms of Statin Therapy for Persons With Chronic Kidney Disease: A Systematic Review and Meta-analysis

Suetonia C. Palmer, MBChB, PhD; Jonathan C. Craig, MBChB, MM, MPH, PhD; Sankar D. Navaneethan, MD, MPH; Marcello Tonelli, MD, PhD; Fabio Pellegrini, MSc; and Giovanni F.M. Strippoli, MD, MM, MPH, PhD
[+] Article and Author Information

From the University of Otago, Christchurch, Christchurch, New Zealand; University of Sydney, Sydney, Australia; Cleveland Clinic, Cleveland, Ohio; University of Alberta, Edmonton, Alberta, Canada; and Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy.

Disclaimer: The authors had full responsibility for collecting and interpreting the data and writing the report. The first and last authors had full access to all data and had the final responsibility of submitting the manuscript for publication.

Potential Conflicts of Interest: Dr. Craig: Membership: SHARP Steering Committee. Dr. Navaneethan: Grants/grants pending: National Institutes of Health, Genzyme. Dr. Tonelli: Board membership: Merck. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M11-3102.

Requests for Single Reprints: Giovanni F.M. Strippoli, MD, MM, MPH, PhD, Department of Clinical Pharmacology and Epidemiology, Consorzio Mario Negri Sud, Via Nazionale 8/a, 66030, Santa Maria Imbaro, Italy; e-mail, strippoli@negrisud.it.

Current Author Addresses: Dr. Palmer: University of Otago, Christchurch, 2 Riccarton Avenue, PO Box 4345, Christchurch 8041, New Zealand.

Dr. Craig: Sydney School of Public Health, University of Sydney, NSW 2006, Australia.

Dr. Navaneethan: Cleveland Clinic, Department of Nephrology and Hypertension, 9500 Euclid Avenue, Q7/155, Cleveland, OH 44195.

Dr. Tonelli: University of Alberta, 7-129 Clinical Sciences Building, Edmonton, Alberta T6G 2G3, Canada.

Mr. Pellegrini and Dr. Strippoli: Consorzio Mario Negri Sud, Via Nazionale 8/a, 66030, Santa Maria Imbaro, Italy.

Author Contributions: Conception and design: S.C. Palmer, J.C. Craig, S.D. Navaneethan, G.F.M. Strippoli.

Analysis and interpretation of the data: S.C. Palmer, J.C. Craig, S.D. Navaneethan, M. Tonelli, F. Pellegrini, G.F.M. Strippoli.

Drafting of the article: S.C. Palmer, J.C. Craig, G.F.M. Strippoli.

Critical revision of the article for important intellectual content: S.C. Palmer, J.C. Craig, S.D. Navaneethan, M. Tonelli, F. Pellegrini, G.F.M. Strippoli.

Final approval of the article: S.C. Palmer, J.C. Craig, S.D. Navaneethan, M. Tonelli, G.F.M. Strippoli.

Provision of study materials or patients: G.F.M. Strippoli.

Statistical expertise: S.C. Palmer, J.C. Craig, F. Pellegrini, G.F.M. Strippoli.

Obtaining of funding: G.F.M. Strippoli.

Administrative, technical, or logistic support: G.F.M. Strippoli.

Collection and assembly of data: S.C. Palmer, S.D. Navaneethan, G.F.M. Strippoli.


Ann Intern Med. 2012;157(4):263-275. doi:10.7326/0003-4819-157-4-201208210-00007
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Background: Statins have uncertain benefits in persons with chronic kidney disease (CKD) because individual trials may have insufficient power to determine whether treatment effects differ with severity of CKD.

Purpose: To summarize the benefits and harms of statin therapy for adults with CKD and examine whether effects of statins vary by stage of kidney disease.

Data Sources: Cochrane and EMBASE databases (inception to February 2012).

Study Selection: Randomized trials comparing the effects of statins with placebo, no treatment, or another statin on mortality and cardiovascular outcomes.

Data Extraction: Two independent reviewers extracted data and assessed risk of bias.

Data Synthesis: Eighty trials comprising 51 099 participants compared statin with placebo or no treatment. Treatment effects varied with stage of CKD. Moderate- to high-quality evidence indicated that statins reduced all-cause mortality (relative risk [RR], 0.81 [95% CI, 0.74 to 0.88]), cardiovascular mortality (RR, 0.78 [CI, 0.68 to 0.89]), and cardiovascular events (RR, 0.76 [CI, 0.73 to 0.80]) in persons not receiving dialysis. Moderate- to high-quality evidence indicated that statins had little or no effect on all-cause mortality (RR, 0.96 [CI, 0.88 to 1.04]), cardiovascular mortality (RR, 0.94 [CI, 0.82 to 1.07]), or cardiovascular events (RR, 0.95 [CI, 0.87 to 1.03]) in persons receiving dialysis. Effects of statins in kidney transplant recipients were uncertain. Statins had little or no effect on cancer, myalgia, liver function, or withdrawal from treatment, although adverse events were evaluated systematically in fewer than half of the trials.

Limitation: There was a reliance on post hoc subgroup data for earlier stages of CKD.

Conclusion: Statins decrease mortality and cardiovascular events in persons with early stages of CKD, have little or no effect in persons receiving dialysis, and have uncertain effects in kidney transplant recipients.

Primary Funding Source: None.

Figures

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Appendix Figure 1.

Summary of evidence search and selection.

CKD = chronic kidney disease; LDL = low-density lipoprotein.

* Data from reference (11).

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Figure 1.

Risk of bias in trials comparing statin regimens with placebo or no treatment.

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Figure 2.

Effect of statin therapy versus placebo or no treatment on total and cardiovascular mortality and major cardiovascular events, by stage of CKD.

CKD = chronic kidney disease.

* “Subsets” refers to the presence of data from subgroups of patients with CKD not receiving dialysis or cohorts receiving various types of dialysis (peritoneal dialysis or hemodialysis) within broader trials.

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Figure 3.

Summary of adverse effects for statins versus placebo or no treatment in persons with CKD (any stage).

CKD = chronic kidney disease.

* “Subsets” refers to subgroups of persons with differing stages of CKD within a single trial for which disaggregated outcome data could be included in the analyses.

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Appendix Figure 2.

Subgroup analysis of potential sources of heterogeneity on effects of statin treatment versus placebo or no treatment for all-cause mortality.

NA = not available.

* “Explained variance” refers to the proportion of variance in the overall treatment effect estimate explained by stage of chronic kidney disease.

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Appendix Figure 3.

Subgroup analysis of potential sources of heterogeneity on effects of statin treatment versus placebo or no treatment for major cardiovascular events.

NA = not available.

* “Explained variance” refers to the proportion of variance in the overall treatment effect estimate explained by stage of chronic kidney disease.

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