Benefits and harms of statin therapy for persons with chronic kidney disease: a systematic review and meta-analysis

Abstract

Background: Statins have uncertain benefits in persons with chronic kidney disease (CKD) because individual trials may have insufficient power to determine whether treatment effects differ with severity of CKD.

Purpose: To summarize the benefits and harms of statin therapy for adults with CKD and examine whether effects of statins vary by stage of kidney disease.

Data sources: Cochrane and EMBASE databases (inception to February 2012).

Study selection: Randomized trials comparing the effects of statins with placebo, no treatment, or another statin on mortality and cardiovascular outcomes.

Data extraction: Two independent reviewers extracted data and assessed risk of bias.

Data synthesis: Eighty trials comprising 51099 participants compared statin with placebo or no treatment. Treatment effects varied with stage of CKD. Moderate- to high-quality evidence indicated that statins reduced all-cause mortality (relative risk [RR], 0.81 [95% CI, 0.74 to 0.88]), cardiovascular mortality (RR, 0.78 [CI, 0.68 to 0.89]), and cardiovascular events (RR, 0.76 [CI, 0.73 to 0.80]) in persons not receiving dialysis. Moderate- to high-quality evidence indicated that statins had little or no effect on all-cause mortality (RR, 0.96 [CI, 0.88 to 1.04]), cardiovascular mortality (RR, 0.94 [CI, 0.82 to 1.07]), or cardiovascular events (RR, 0.95 [CI, 0.87 to 1.03]) in persons receiving dialysis. Effects of statins in kidney transplant recipients were uncertain. Statins had little or no effect on cancer, myalgia, liver function, or withdrawal from treatment, although adverse events were evaluated systematically in fewer than half of the trials.

Limitation: There was a reliance on post hoc subgroup data for earlier stages of CKD.

Conclusion: Statins decrease mortality and cardiovascular events in persons with early stages of CKD, have little or no effect in persons receiving dialysis, and have uncertain effects in kidney transplant recipients.

Figures

Figure 1

Risk of bias in trials comparing statin regimens with placebo or no treatment

Figure 2

Effect of statin therapy versus placebo or no treatment control on total and cardiovascular mortality and major cardiovascular events, grouped by stage of chronic kidney disease. 95% CI, 95% confidence interval; CKD, chronic kidney disease. *Subsets of trials refers to presence of data from subgroups with chronic kidney disease not on dialysis or cohorts on various types of dialysis (peritoneal dialysis or hemodialysis) within broader trials

Figure 3

Summary of adverse effects for statins versus placebo or no treatment control in people with chronic kidney disease (any stage). 95% CI, 95% confidence interval; CKD, chronic kidney disease