HMG CoA reductase inhibitors (statins) for kidney transplant recipients

Abstract

Background: Cardiovascular deaths account for the majority of deaths in kidney transplant recipients and dyslipidaemia contributes significantly to their cardiovascular disease. Statins are widely used in kidney transplant patients given their established benefits in the general population, however evidence favouring their use is lacking.

Objectives: To assess the benefits and harms of statin therapy on mortality and renal outcomes in kidney transplant recipients.

Search strategy: We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), and hand searched reference lists of articles and scientific proceedings.

Selection criteria: Randomised controlled trials (RCTs) and quasi-RCTs comparing statins with placebo, no treatment or other statins in kidney transplant recipients.

Data collection and analysis: Two authors independently assessed study quality and extracted data. Statistical analyses were performed using the random effects model after testing for heterogeneity. Results were expressed as mean difference (MD) for continuous outcomes (lipid parameters) and risk ratio (RR) for dichotomous outcomes (mortality, allograft rejection, liver enzymes, occurrence of rhabdomyolysis and study withdrawal) with 95% confidence intervals (CI).

Main results: Sixteen studies (3229 patients) comparing statins versus placebo (15) or another statin (1) were included. Compared to placebo, statins did not decrease all-cause mortality (14 studies: RR 1.30, 95% CI 0.54 to 3.12). Point estimates favoured statins in terms of cardiovascular mortality (13 studies: RR 0.68, 95% CI 0.46 to 1.03) and non-fatal cardiovascular events (1 study: RR 0.70, 95% CI 0.48 to 1.01), however the results were not statistically significant. Compared to placebo, the use of statins was associated with a significantly lower end of treatment average total cholesterol (10 studies: MD -42.33 mg/dL (1.26 mmol/L), 95% CI -53.02 to -31.64), LDL cholesterol (10 studies: MD -46.15 mg/dL (1.19 mmol/L), 95% CI -55.97 to -36.33) and triglycerides (10 studies: MD -25.46 mg/dL (0.26 mmol/L), 95% CI -33.95 to 16.9). There was no significant difference in the risk of acute rejection (5 studies: RR 0.61; 95% C.I.0.32 to 1.16.) No data on chronic rejection was available and no major toxicity was noted.

Authors' conclusions: Statins significantly reduced hyperlipidaemia and tended to reduce cardiovascular events in kidney transplant recipients, but no effect has yet been demonstrated for mortality outcomes. Most of the data was derived from one large long-term study. Considering the significant impact of statins on all-cause and cardiovascular mortality in the general and predialysis populations, more studies are needed in kidney transplant patients.