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High-quality evidence suggests that chronic kidney disease (CKD) should now be considered a coronary heart disease (CHD) risk equivalent. Although statin therapy consistently reduces coronary events in the general population, the clinical benefits of lipid lowering in persons with CKD are less certain. Although multiple studies have shown possible benefit from statin therapy in early-stage CKD patients, there has been a recent concern that patients with more severe CKD, such as those on dialysis, do not seem to benefit.
The authors identified randomised controlled trials with statins from a previously published meta-analysis,1 and supplemented it with recent trials identified in EMBASE, the Cochrane Central Register of Controlled Trials and the Cochrane Renal Group's Specialised Registry up to February 2012. The inclusion criteria was trials comparing the effects of a statin versus either a placebo or no treatment control in adults with CKD (any stage) with a follow-up period of greater than 8 weeks and outcomes including mortality and cardiovascular (CV) outcomes. Two independent reviewers extracted data and assessed the risk of bias. Outcomes measured included total and CV mortality and major CV events (fatal or non-fatal myocardial infarction or stroke). Subgroups of CKD patients (no dialysis, dialysis or kidney transplant recipient) were analysed separately.
Eighty trials comprising 51 099 participants (with median follow-up of 6 months) compared statin with placebo or no treatment. Overall, treatment benefits seemed to vary with stage of CKD (no dialysis, dialysis or kidney transplant recipient). Moderate-quality to high-quality evidence indicated that statin treatment in persons not receiving dialysis scored favourably in all outcomes: all-cause mortality (relative risk (RR) 0.81, 95% CI 0.74 to 0.88), CV mortality (RR, 0.78, 95% CI 0.68 to 0.89) and major CV events (RR 0.76, 95% CI 0.73 to 0.80). In absolute terms, five deaths per year could be prevented if 1000 non-dialysis patients with CKD were treated with statin therapy. However, statin treatment in patients receiving dialysis had either little or no effect or uncertain treatment effects as was also seen for kidney transplant recipients. An analysis of study heterogeneity showed that the stage of CKD explained the majority of the variation in outcomes.
This meta-analysis updates a previous meta-analysis performed in 20081 by including several new statin clinical trials in patients with a wider spectrum of CKD severity. Because of sample size and power issues, prior meta-analysis was unable to discern a difference in CKD outcomes by stage of CKD. In particular prior meta-analysis relied heavily on CKD subgroups from large lipid trials in the general population and thus generally included those with early or less severe CKD. With the inclusion of new clinical trials in dialysis and non-dialysis patients, difference in outcomes by CKD stage has become much clearer. This well-conducted meta-analysis serves to fill the prior void in the knowledge base about the roles of statins in CKD by providing two important pieces of new information: that although statins do not seem to improve CV events or mortality outcomes in patients receiving dialysis, they do seem to significantly improve CV events and mortality in patients with CKD stages 1–4. In the current meta-analysis, by including the large number of dialysis (n=3023) and non-dialysis patients (n=6247) from the SHARP trial,2 a larger number of CKD patients with moderate and severe CKD could be evaluated. Thus, the current meta-analysis suggests potential benefits in both early CKD (stages 1 and 2) and more advanced CKD (stages 3 and 4) as well.
The analysis presented did have some limitations. First, the patient populations studied were very heterogeneous as were the interventions (type of statin and dose), and the prespecified outcomes reported. Second, it is unclear whether revascularisations were analysed separately as part of the endpoint of major CV events. This could have overestimated the CV benefits in CKD patients if the CV benefit was mainly driven by the reduction in revascularisations.
This study makes a compelling argument that clinicians should consider the use of statins in most patients at any stage of CKD, but not in those on dialysis. The results for dialysis patients reflect mainly those on haemodialysis and should not be generalised to those on peritoneal dialysis. Statins are clearly underutilised in CKD patients, despite their high risk of CV events. Given that CKD should now be considered a CHD-risk equivalent, this meta-analysis gives further support for the more aggressive use of statins in CKD patients given their impressive track record in both benefits and safety.
Competing interests None.