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BMC Nephrology
Published in: BMC Nephrology 1/2017

Open Access 01-12-2017 | Research article

Effect on non-vascular outcomes of lowering LDL cholesterol in patients with chronic kidney disease: results from the Study of Heart and Renal Protection

Authors: C. Reith, N. Staplin, W. G. Herrington, W. Stevens, J. Emberson, R. Haynes, M. Mafham, J. Armitage, A. Cass, J. C. Craig, L. Jiang, T. Pedersen, C. Baigent, M. J. Landray, on behalf of the SHARP Collaborative Group

Published in: BMC Nephrology | Issue 1/2017

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Abstract

Background

Reducing LDL cholesterol (LDL-C) with statin-based therapy reduces the risk of major atherosclerotic events among patients with chronic kidney disease (CKD), with no evidence of an excess risk of cancer or death from any non-vascular cause. However, non-randomized data have suggested that statin therapy may have effects (both adverse and beneficial) on particular non-vascular conditions that do not cause death.

Methods

The Study of Heart and Renal Protection (SHARP) randomized patients with CKD to simvastatin 20 mg plus ezetimibe 10 mg (simvastatin/ezetimibe) daily versus matching placebo. Participants were followed up at least 6 monthly and all post-randomization serious adverse events (SAEs) were recorded. This supplementary analysis reports the effects of treatment on non-vascular SAEs, overall, by system of disease, by baseline characteristics, and by duration of follow-up.

Results

During a median of 4.9 years follow-up, similar numbers of participants in the two groups experienced at least one non-vascular SAE (3551 [76.4%] simvastatin/ezetimibe vs 3537 [76.6%] placebo; risk ratio [RR] 0.99, 95% confidence interval [CI] 0.95–1.04). There was no good evidence of any significant effect of simvastatin/ezetimibe on SAEs attributed to any particular nonvascular disease system (of 43 comparisons, only 3 yielded an uncorrected p value < 0.05, of which the smallest was p = 0.02). The relative risk of any nonvascular SAE did not vary significantly among particular prognostic subgroups or by duration of follow-up.

Conclusions

In the SHARP trial, allocation to simvastatin/ezetimibe combination therapy was not associated with any significant non-vascular hazard.

Trials registration

SHARP was retrospectively registered after the first participant was enrolled in 2003 at ISRCTN (ISRCTN54137607 on 31 January 2005: http://www.isrctn.com/ISRCTN54137607) and ClinicalTrials.gov (NCT00125593 on 29 July 2005: https://clinicaltrials.gov/ct2/show/NCT00125593).
Appendix
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Metadata
Title
Effect on non-vascular outcomes of lowering LDL cholesterol in patients with chronic kidney disease: results from the Study of Heart and Renal Protection
Authors
C. Reith
N. Staplin
W. G. Herrington
W. Stevens
J. Emberson
R. Haynes
M. Mafham
J. Armitage
A. Cass
J. C. Craig
L. Jiang
T. Pedersen
C. Baigent
M. J. Landray
on behalf of the SHARP Collaborative Group
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Nephrology / Issue 1/2017
Electronic ISSN: 1471-2369
DOI
https://doi.org/10.1186/s12882-017-0545-2

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