Effects of statins in patients with chronic kidney disease: meta-analysis and meta-regression of randomised controlled trials

Abstract

Objective: To analyse the benefits and harms of statins in patients with chronic kidney disease (pre-dialysis, dialysis, and transplant populations).

Design: Meta-analysis.

Data sources: Cochrane Central Register of Controlled Trials, Medline, Embase, and Renal Health Library (July 2006).

Study selection: Randomised and quasi-randomised controlled trials of statins compared with placebo or other statins in chronic kidney disease.

Data extraction and analysis: Two reviewers independently assessed trials for inclusion, extracted data, and assessed trial quality. Differences were resolved by consensus. Treatment effects were summarised as relative risks or weighted mean differences with 95% confidence intervals by using a random effects model.

Results: Fifty trials (30 144 patients) were included. Compared with placebo, statins significantly reduced total cholesterol (42 studies, 6390 patients; weighted mean difference -42.28 mg/dl (1.10 mmol/l), 95% confidence interval -47.25 to -37.32), low density lipoprotein cholesterol (39 studies, 6216 patients; -43.12 mg/dl (1.12 mmol/l), -47.85 to -38.40), and proteinuria (g/24 hours) (6 trials, 311 patients; -0.73 g/24 hour, -0.95 to -0.52) but did not improve glomerular filtration rate (11 studies, 548 patients; 1.48 ml/min (0.02 ml/s), -2.32 to 5.28). Fatal cardiovascular events (43 studies, 23 266 patients; relative risk 0.81, 0.73 to 0.90) and non-fatal cardiovascular events (8 studies, 22 863 patients; 0.78, 0.73 to 0.84) were reduced with statins, but statins had no significant effect on all cause mortality (44 studies, 23 665 patients; 0.92, 0.82 to 1.03). Meta-regression analysis showed that treatment effects did not vary significantly with stage of chronic kidney disease. The side effect profile of statins was similar to that of placebo. Most of the available studies were small and of suboptimal quality; mortality data were provided by a few large trials only.

Conclusion: Statins significantly reduce lipid concentrations and cardiovascular end points in patients with chronic kidney disease, irrespective of stage of disease, but no benefit on all cause mortality or the role of statins in primary prevention has been established. Reno-protective effects of statins are uncertain because of relatively sparse data and possible outcomes reporting bias.

Fig 1 Flow chart showing number of citations retrieved by individual searches and number of trials included in review

Fig 2 Effect of statins compared with placebo or no treatment on all cause mortality in pre-dialysis, dialysis, and transplant patients. Almost all studies reported mortality data, but no events were detected in many studies; only studies in which events were detected are included in the plot

Fig 3 Effect of statins compared with placebo or no treatment on cardiovascular mortality in pre-dialysis, dialysis, and transplant patients. Only studies with at least one event are included in the plot

Fig 4 Effect of statins compared with placebo or no treatment on cardiovascular events in pre-dialysis, dialysis, and transplant patients. Only studies with at least one event are included in the plot

Fig 5 Effect of statins compared with placebo or no treatment on acute allograft rejection in renal transplant recipients

Fig 6 Withdrawal rates for statins compared with placebo in pre-dialysis, dialysis, and transplant patients. Only studies with at least one withdrawal are included in the plot