We aimed to evaluate the benefits (reductions in all-cause and cardiovascular mortality, major cardiovascular events,
myocardial infarction and
stroke, and progression of CKD to requiring dialysis) and harms (muscle or
liver dysfunction, withdrawal,
cancer) of
statins compared to placebo, no treatment, standard care, or another
statin in adults with CKD who have a functioning kidney transplant.
SEARCH METHODS: We searched the Cochrane Renal Group's Specialised Register to 29 February 2012 through contact with the Trials Search Co-ordinator using search terms relevant to this review.
SELECTION CRITERIA: Two authors independently extracted data and assessed risk of bias. Treatment effects were expressed as mean difference (MD) for continuous outcomes (
lipids, glomerular filtration rate (GFR),
proteinuria) and relative risk (RR) for dichotomous outcomes (major cardiovascular events, mortality, fatal or non-fatal
myocardial infarction, fatal or non-fatal
stroke, elevated muscle or liver
enzymes, withdrawal due to adverse events,
cancer,
end-stage kidney disease (ESKD), acute allograft rejection) together with 95% confidence intervals (CI).
MAIN RESULTS: We identified 22 studies (3465 participants); 17 studies (3282 participants) compared
statin with placebo or no treatment, and five studies (183 participants) compared two different
statin regimens.From data generally derived from a single high-quality study, it was found that
statins may reduce major cardiovascular events (1 study, 2102 participants: RR 0.84, CI 0.66 to 1.06), cardiovascular mortality (4 studies, 2322 participants: RR 0.68, CI 0.45 to 1.01), and fatal or non-fatal
myocardial infarction (1 study, 2102 participants: RR 0.70, CI 0.48 to 1.01); although effect estimates lack precision and include the possibility of no effect.Statins had uncertain effects on all-cause mortality (6 studies, 2760 participants: RR 1.08, CI 0.63 to 1.83); fatal or non-fatal
stroke (1 study, 2102 participants: RR 1.18, CI 0.85 to 1.63);
creatine kinase elevation (3 studies, 2233 participants: RR 0.86, CI 0.39 to 1.89); liver
enzyme elevation (4 studies, 608 participants: RR 0.62, CI 0.33 to 1.19); withdrawal due to adverse events (9 studies, 2810 participants: RR 0.89, CI 0.74 to 1.06); and
cancer (1 study, 2094 participants: RR 0.94, CI 0.82 to 1.07).
Statins significantly reduced serum total
cholesterol (12 studies, 3070 participants: MD -42.43 mg/dL, CI -51.22 to -33.65);
low-density lipoprotein cholesterol (11 studies, 3004 participants: MD -43.19 mg/dL, CI -52.59 to -33.78); serum
triglycerides (11 studies, 3012 participants: MD -27.28 mg/dL, CI -34.29 to -20.27); and lowered
high-density lipoprotein cholesterol (11 studies, 3005 participants: MD -5.69 mg/dL, CI -10.35 to -1.03).
Statins had uncertain effects on kidney function: ESKD (6 studies, 2740 participants: RR 1.14, CI 0.94 to 1.37);
proteinuria (2 studies, 136 participants: MD -0.04 g/24 h, CI -0.17 to 0.25); acute allograft rejection (4 studies, 582 participants: RR 0.88, CI 0.61 to 1.28); and GFR (1 study, 62 participants: MD -1.00 mL/min, CI -9.96 to 7.96).Due to heterogeneity in comparisons, data directly comparing differing
statin regimens could not be meta-analysed. Evidence for
statins in people who have had a kidney transplant were sparse and lower quality due to imprecise effect estimates and provided limited systematic evaluation of treatment harm.
AUTHORS' CONCLUSIONS:
Statins may reduce cardiovascular events in kidney transplant recipients, although treatment effects are imprecise.
Statin treatment has uncertain effects on overall mortality,
stroke, kidney function, and toxicity outcomes in kidney transplant recipients. Additional studies would improve our confidence in the treatment benefits and harms of
statins on cardiovascular events in this clinical setting.