The Issue of Statin Safety

Abstract

Statins are first-line therapy for reducing low-density lipoprotein (LDL) levels in patients at high risk for atherosclerotic cardiovascular disease (ASCVD).1,2 These agents are being used in millions of high-risk people worldwide. Many others receive statins for primary prevention. The total number can only be expected to rise with time. Although favorable results from a large number of controlled clinical trials underpin the benefits of statin therapy,2 it is not surprising that the safety of statins has received much attention. Controlled trials and clinical practice have demonstrated that they generally are safe; in fact, the frequency of clinically significant side effects is quite low. In rare patients, nonetheless, side effects can occur and occasionally are serious. Most serious among these is severe myopathy (rhabdomyolysis), which can cause acute renal failure. In a small percentage of patients, statins elevate serum transaminases. There is little or no evidence that statins cause progressive liver disease3; nevertheless, persistent elevations in transaminases can be perplexing. Other less serious side effects may occur. One of these that was demonstrated recently is low-grade proteinuria, likely due to a statin-induced inhibition of proximal tubular reabsorption of protein.4 To date, no evidence exists that this is accompanied by pathological tubular injury or progression to chronic renal failure. See p 3051 Side effects of statins tend to be dose related. Most side effects, including myopathy, disappear on withdrawal of the medication. Even with severe myopathy, most patients survive with supportive measures, although fatalities occasionally occur. For example, Omar and Wilson5 reported that between November 1997 and March 2000, 871 cases of statin-associated severe myopathy were reported to the US Food and Drug Administration (FDA); among these reports, however, only 38 cases were listed as fatal. Six statins currently are available by prescription in the United …