All non-vascular SAEs, by particular baseline characteristics. Figure S2. All non-vascular SAEs, by system of disease and dialysis status. Figure S3. All non-vascular SAEs, by duration of follow-up. (PDF 21 kb

A. Cass

C. Baigent

C. Reith

J. Armitage

J. C. Craig

J. Emberson

L. Jiang

M. J. Landray

M. Mafham

N. Staplin

on behalf of the SHARP Collaborative Group

R. Haynes

T. Pedersen

W. G. Herrington

W. Stevens

BMC Nephrology

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)

Reith, C.

Staplin, N.

Herrington, W. G

Stevens, W.

Emberson, J.

Haynes, R.

Mafham, M.

Armitage, J.

Cass, A.

Craig, J. C

Jiang, L.

Pedersen, T.

Baigent, C.

Landray, M. J

NORA - Norwegian Open Research Archives

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

Reith, Christina

Staplin, Natalie

Herrington, Will

Stevens, Will

Emberson, Jonathan

Haynes, Richard

Mafham, Marion

Armitage, Jane

Cass, A

Craig, JC

Jiang, L

Pedersen, T

Baigent, Colin

Landray, Martin

Oxford University Research Archive

Effect on non-vascular outcomes of lowering LDL cholesterol in patients with chronic kidney disease:  Results from the study of heart and renal protection

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)

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C. Reith (3991310)

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J. Emberson (3991316)

R. Haynes (3417065)

M. Mafham (3991328)

J. Armitage (3991304)

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J. Craig (3991319)

L. Jiang (42921)

T. Pedersen (3991313)

C. Baigent (3991334)

M. Landray (3991322)

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Additional file 1: of Effect on non-vascular outcomes of lowering LDL cholesterol in patients with chronic kidney disease: results from the Study of Heart and Renal Protection