Statin use after renal transplantation: a systematic quality review of trial-based evidence.
OBJECTIVE
HMG-CoA reductase inhibitor (statin) therapy reduces cardiovascular risk in the general population and may modulate rejection in solid organ transplant recipients. We assessed whether current clinical evidence supports the use of statins to improve cardiac and/or renal outcomes after kidney transplantation.


METHODS
We performed a systematic review of randomized, controlled intervention trials of statins among renal allograft recipients. Clinical trials published between January 1, 1993 and January 1, 2004 were identified by systematic search of electronic databases. Eligible studies measured the impact of therapy on acute allograft rejection, surrogates of cardiovascular risk and/or cardiovascular morbidity and mortality. We abstracted descriptive summaries of trial design elements and primary effect estimates, and assessed trial quality with a standardized quality evaluation tool.


RESULTS
Thirteen eligible trials were identified. Statin therapy was associated with less acute allograft rejection in two early studies but was ineffective in three subsequent, larger trials. Therapeutic benefit was also seen in six of seven small studies that evaluated cardiovascular risk surrogates. Statin use did not significantly alter the primary composite outcome in a single large cardiac events trial, but was associated with reductions in secondary end-points of cardiac death analysed alone or with myocardial infarction. Important design distinctions included statin preparation and dose, concomitant interventions, study power and randomization methods. Median total quality scores were 52 for the rejection trials, 41 for the studies of cardiovascular risk surrogates and 69 for the cardiac events trial, and showed a trend towards variation by outcome measure (P = 0.05).


CONCLUSIONS
Heterogeneous study designs and methodological quality contribute to discrepant conclusions on the benefit of statin therapy to renal allograft recipients. Trial-based clinical evidence does not support the use of statins to lower acute rejection risk after kidney transplantation, but does indicate effectiveness for improvement in cardiovascular risk markers and possibly for reduction of clinical cardiac events.
Lentine
Krista L
KL
Division of Nephrology, Washington University Medical Center, Campus Box 8219, 660 S. Euclid Avenue, St Louis, MO 63110, USA. lentine.krista@stanfordalumni.org
Brennan
Daniel C
DC
D002318:Cardiovascular Diseases / Q000517:prevention & control; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007674:Kidney Diseases / Q000517:prevention & control; D016030:Kidney Transplantation; D016032:Randomized Controlled Trials as Topic
D004791:Enzyme Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors