Statins are the most commonly prescribed drugs for lowering low-density lipoprotein (LDL) cholesterol levels. They’ve been amply studied in phase 3, randomized clinical trials and have been shown in primary and secondary prevention trials to reduce the risk of cardiovascular events. Statin use has increased dramatically in the past decade and will probably increase further because of lowered LDL cholesterol goals, new indications for treatment (increased C-reactive protein levels despite low or normal LDL levels), the introduction of generic versions of brand-name statins, and treatment recommendations for younger age groups. And since statin use has become the standard of care, pay-for-performance incentives may begin to incorporate the prescribing of statins in order to meet pre established targets for health care delivery. Yet all statins are associated with adverse events, especially at higher doses. Muscle-related adverse events, cognitive and memory problems, and elevation of liver enzymes have all been described. Such events reportedly occur with a frequency of less than 5% among patients in randomized clinical trials but in as many as 20% of patients in clinical practice. 1 The discrepancy may be largely attributable to patient selection in randomized trials, which may exclude older subjects or enroll insufficient numbers of women, two groups reported to have a higher incidence of statinrelated adverse events. Patients who consume substantial amounts of alcohol, have multiple coexisting conditions, or take several other medications are also generally excluded. In clinical practice, however, such patients might well be prescribed statins. It’s unlikely that a randomized clinical trial would or could be designed to include all these patients. Another reason for the discrepancy in the reported frequency of adverse events may be the lack of a standard definition for statinassociated myopathy, the most common adverse event. Elevated serum creatine kinase levels (at least 10 times the upper limit of the normal range) are typically used to identify statin-associated myopathy in most studies, but this condition is not necessarily accompanied by elevated serum creatine kinase levels. 2 In addition, statin-associated myopathy may present not only as pain, but also as fatigability and weakness, which are not assessed in routine physical examination. Impaired cognition, the most common neurologic problem associated with statin use, is also not measured in most clinical settings, and reports of such symptoms are often dismissed as related to aging.

Possible further evidence of statin toxicity comes from the low rates of adherence to statin therapy over a 2-year period—25.4% among patients taking the statin for primary prevention and 40.1% among patients taking it because of a history of coronary disease. 3 It’s been assumed that poor adherence is due to barriers to therapy, but the occurrence of adverse events is also a possibility. Whether the frequency of adverse events is closer to 5% or 20%, statins are used so widely that side effects can translate into substantial public health problems.