Intolerance to Statins: Mechanisms and Management

S tatins are considered very effectivein reducing cardiovascular morbid-ity and mortality in high-risk pa-tients. However, although adherence to statins improves morbidity and mortality (1), it remains suboptimal (2). One of the most important causes of nonadherence is the so-called statin intolerance, mainly because of muscle-related symptoms. These symptoms most often consist of myalgia unaccompanied by significant creatine kinase (CK) elevations. Less of-ten, myositis (elevated CK.10 times the upper limit of normal) or rhabdomyolysis (CK level.10,000 IU/L or accompanied by significant elevation in creatinine level) develops. In randomized controlled trials, the incidence of statin myopathy is ~1.5– 5.0 % (3). However, this low incidence may be misleading for several reasons. First, in most studies patients with a his-tory of statin intolerance were excluded. Other studies had a single-blinded statin run-in phase, and patients experiencing muscle-related symptoms or CK eleva-tions during this phase were excluded. Patients who tend to be at risk for devel-oping muscle-related symptoms, such as women, elderly patients, and patients with significant comorbidity, who com-prise a large proportion of statin-treated patients in real-life settings, are underrep-resented in randomized controlled trials. Some studies have definedmuscle-related effects by elevated CK levels only, disre-garding myalgia. Last but not least, pa-tients enrolled in studies might be motivated and so minimize reporting of mild myalgias, thus leading to underesti-mation of the magnitude of the problem. Data concerning real-life incidence of statin-related myopathy are scarce. In the