BACKGROUND: Muscle pain without elevation of serum creatine phosphokinase (CPK) 
(myalgia) is the most common medication-related adverse effect of statin 
therapy; it occurs in up to 10% of patients who are prescribed statin therapy. 
Although much is known regarding risk factors for overt myositis, very few 
studies have provided information on this common form of statin intolerance.
METHODS: We defined a detailed clinical and laboratory phenotype of a cohort of 
patients referred to the lipid clinic of a governmental health maintenance 
organization for statin intolerance attributable to muscle pain without CPK 
elevation (myalgia) and characterized their response to alternative 
lipid-lowering therapy. Baseline and follow-up data were analyzed for 104 
patients with statin intolerance attributable to myalgia and 211 statin-tolerant 
control patients identified from the referral population.
RESULTS: Among patients with myalgia, more were white and had hypertension. The 
prevalence of known risk factors for overt myositis, including renal disease, 
type 2 diabetes mellitus, thyroid disease, and electrolyte abnormalities, did 
not differ between statin intolerant and statin tolerant patients. Although 
individual cases were identified in which the addition of interacting 
medications was temporally associated with development of statin intolerance, 
overall use of interacting medications was not more frequent among 
statin-intolerant patients. The majority of patients were intolerant of two or 
more statins; however, in more than one-half the cases, successful rechallenge 
with an alternative statin was accomplished. Despite this and extensive use of 
nonstatin lipid medications after lipid clinic referral, control of plasma 
lipoproteins remained significantly worse in statin-intolerant patients.
CONCLUSIONS: Statin intolerance attributable to myalgia is a significant barrier 
to effective treatment of hyperlipidemia. Conventional clinical risk factors for 
myositis do not appear to predictive of statin-associated myalgia. These 
findings underscore the need to better define the pathophysiology of 
statin-induced myalgia and develop methodologies to guide treatment of 
statin-intolerant patients.