Key result
Simvastatin plus ezetimibe shows no difference in non-vascular serious adverse events versus placebo in CKD.
Why the study?
Reducing LDL cholesterol with statin-based therapy reduces vascular risk in CKD patients, but effects on non-vascular serious adverse events remain uncertain.
RCT (n=9,270)
Double-blind
4:4:1 ratio initially, then re-randomized at one year
Yes
Relative Risk: 0.99 (95% CI 0.95–1.04)
Absolute Event Rate: 76.4% vs 76.6%
p-value: p=0.82
Similar non-vascular SAE rates in CKD merit no practice change; leaves open randomized validation.
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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Reith et al. (2017) conducted an RCT in Chronic kidney disease (n=9,270). Simvastatin plus ezetimibe vs. Matching placebo was evaluated on At least one non-vascular serious adverse event (SAE) (RR 0.99, 95% CI 0.95-1.04, p=0.82). In patients with chronic kidney disease, simvastatin plus ezetimibe did not significantly alter the risk of experiencing at least one non-vascular serious adverse event compared to placebo (RR 0.99).
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