Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors)
are associated with skeletal muscle complaints, including clinically important
myositis and rhabdomyolysis, mild serum creatine kinase (CK) elevations, myalgia
with and without elevated CK levels, muscle weakness, muscle cramps, and persistent
myalgia and CK elevations after statin withdrawal. We performed a literature
review to provide a clinical summary of statin-associated myopathy and discuss
possible mediating mechanisms. We also update the US Food and Drug Administration
(FDA) reports on statin-associated rhabdomyolysis. Articles on statin myopathy
were identified via a PubMed search through November 2002 and articles on
statin clinical trials, case series, and review articles were identified via
a PubMed search through January 2003. Adverse event reports of statin-associated
rhabdomyolysis were also collected from the FDA MEDWATCH database. The literature
review found that reports of muscle problems during statin clinical trials
are extremely rare. The FDA MEDWATCH Reporting System lists 3339 cases of
statin-associated rhabdomyolysis reported between January 1, 1990, and March
31, 2002. Cerivastatin was the most commonly implicated statin. Few data are
available regarding the frequency of less-serious events such as muscle pain
and weakness, which may affect 1% to 5% of patients. The risk of rhabdomyolysis
and other adverse effects with statin use can be exacerbated by several factors,
including compromised hepatic and renal function, hypothyroidism, diabetes,
and concomitant medications. Medications such as the fibrate gemfibrozil alter
statin metabolism and increase statin plasma concentration. How statins injure
skeletal muscle is not clear, although recent evidence suggests that statins
reduce the production of small regulatory proteins that are important for
myocyte maintenance.