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

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, SHARP Collaborative Group, 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, SHARP Collaborative Group

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://ichgcp.net/clinical-trials-registry/NCT00125593).

Figures

Fig. 1
Fig. 1
All SAEs, by system of disease and outcome
Fig. 2
Fig. 2
All non−vascular SAEs, by system of disease with sub−categories

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