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ABSTRACT
Objectives: Atherosclerosis is common in patients with chronic kidney disease (CKD), and cardiovascular disease (CVD) represents a major cause of death. The National Kidney Foundation guidelines favour the use of statin therapy for treatment of dyslipidaemia in patients with CKD. Much evidence supports statin therapy for reducing CVD and improving outcomes in the general population, but there is less evidence in patients with CKD. Consequently, prevention of CVD in CKD is based primarily on extrapolation from non-CKD trials. Significantly, in trials specifically designed to investigate patients with CKD, evidence is emerging for improved cardiovascular outcomes with statin therapy. This review describes available data relating to cardiovascular outcomes and the role of statins in patients with CKD, including pre-dialysis, dialysis, and renal transplant patients.
Research design and methods: The PubMed database was searched (1998–present) to ensure comprehensive identification of publications (including randomised clinical trials) relevant to CKD patients, patterns of cardiovascular outcome in such patients and their relationship to lipid profile, and the role of statins for the prevention and treatment of cardiovascular complications.
Results: There are conflicting data on the relationship between dyslipidaemia and cardiovascular outcomes, with one major study of statin therapy (4D – Deutsche Diabetes Dialyse Studie) providing equivocal results. Further studies, including AURORA (A study to evaluate the Use of Rosuvastatin in subjects On Regular haemodialysis: an Assessment of survival and cardiovascular events; NCT00240331) in patients receiving haemodialysis, and SHARP (Study of Heart And Renal Protection; NCT00125593) in patients with CKD including those on dialysis, should help to clarify the role of statin therapy in these populations.
Conclusions: More studies are needed to elucidate the role of statins in improving cardiovascular outcomes for CKD patients. It is anticipated that ongoing clinical trials geared towards the optimal prevention and treatment of CVD in patients with CKD will help guide clinicians in the management of CKD.
Acknowledgments
Declaration of interest: This review was funded by AstraZeneca. B. F. has acted as consultant, advisor or speaker for AstraZeneca, Novartis, Roche, Wyeth, Fujisawa/Astellas, Pfizer, Bayer, and Smith-Kline-Beecham and has received research grants from AstraZeneca, Novartis, Wyeth, Fujisawa/Astellas, and Merck-Schering-Plough. H. H. has received consultancy honoraria or research grants from AstraZeneca, Novartis, Roche, and Wyeth within the last 5 years. F. Z. has acted as a consultant or speaker on occasions for Servier, Novartis, Pfizer, Merck, AstraZeneca, and Boehringer Ingelheim, and has received research funding from Pfizer and Medtronic. A. G. J. has acted as a consultant or speaker on occasions for Novartis, Astellas, Roche, Wyeth, MSD, and AstraZeneca, and has received research funding from AstraZeneca, Novartis, and Wyeth. R. E. S. has consulted for and lectured on behalf of AstraZeneca and has been involved in clinical trials, receiving research support from AstraZeneca. M. K. S. and M. G. are employees of AstraZeneca Sweden.
We thank Neil Venn from Prime Medica Ltd., who provided medical writing support (no competing interests), funded by AstraZeneca. Other than M. K. S. and M. G., who are authors of the review, certain AstraZeneca employees were permitted to read the article before submission and make suggestions, but all final decisions regarding content were the responsibility of the authors. Responsibility for all opinions, conclusions, and interpretation of data lies with the authors.
Executive Steering Committee of the AURORA study: B. Fellström (Principal Investigator; Uppsala, Sweden), F. Zannad (Toul, France), R. Schmieder (Erlangen, Germany), H. Holdaas (Oslo, Norway), A. Jardine (Glasgow, UK).