3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors and rhabdomyolysis: considerations in the renal failure patient.

An intense debate has developed as to the risk-benefit ratio of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) following the withdrawal of cerivastatin. The development of rhabdomyolysis in cerivastatin-treated patients should have surprised few since myotoxicity is an accepted class effect of statins. What has sprung from the cerivastatin experience though is a concern for other members of this class. Such misgivings, although understandable, are ill advised. Without question, differences exist in the risk of rhabdomyolysis occurrence amongst the various statins. In this regard, pravastatin and fluvastatin are least likely to produce rhabdomyolysis, which, in part, relates to the fact they are not metabolized by the cytochrome P450 3A4 pathway. When muscle damage occurs with statins it is most often the result of a drug-drug interaction rather than a specific adverse response to statin monotherapy. Such drug-drug interactions increase plasma concentrations of a statin and thereby increase the risk of myotoxicity. A growing consensus exists which supports an expanded use of statins in a range of patient groups including the renal failure patient. Polypharmacy and altered drug metabolism increase the risk of myotoxicity, albeit to an ill-defined degree, in this population. Many factors should enter into the choice of a statin in the multiply medicated renal failure patient.