Managing Statin Myopathy

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Approximately 10% of patients treated with statins experience some form of muscle-related side effects in clinical practice. These can range from asymptomatic creatine kinase (CK) elevation, to muscle pain, weakness, and its most severe form, rhabdomyolysis. Higher risk patients for statin myopathy are those older than 80, with a small body frame, on higher statin doses, on other medications, or with other systemic diseases including hepatic or renal diseases, diabetes mellitus, or hypothyroidism. The cause of statin myopathy is presumed to be the same for its variable presentation but has not been defined. In patients with myopathic symptoms, their symptoms and CK levels determine whether statin therapy can be continued or must be stopped.

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Definition of terms

Different groups have offered different definitions for the symptoms and findings of statin myopathy. The American College of Cardiology/American Heart Association/National Heart, Lung, and Blood Institute (ACC/AHA/NHLBI) Clinical Advisory on statins defined myopathy as any muscle disease; myalgia as muscle ache or weakness without increased serum CK levels; myositis as muscle symptoms with elevated CK levels; and rhabdomyolysis as muscle symptoms with marked CK elevations (>10 times upper

The incidence of statin-related myopathy

It is difficult to discern the incidence of statin myopathy for a variety of reasons. Severe rhabdomyolysis is extremely rare and, as discussed, lower levels of CK increases are rarely reported in clinical trials. Few early studies elicited myopathic complaints in the absence of CK increases, and most studies have avoided recruiting subjects with risk factors for myopathy. Muscle strength has not been tested in any clinical trials. There also seems to be a gap between the low incidence of

The risk factors for statin myopathy

Most of the information on factors that increase the risk of statin myopathy is based on studies examining the incidence of clinically important rhabdomyolysis and myositis. Few studies have examined risk factors for the more minor myopathic symptoms including myalgia, CK increases less than 10 fold, and muscle cramps. It is generally assumed, but unproven, that the same risk factors contribute to all myopathic symptoms.

Factors that increase the risk of statin myopathy include conditions that

The pathophysiological mechanisms of statin-induced myopathy

The cause of statin-induced myopathy is unknown and it is not certain that the same metabolic changes produce the entire spectrum of statin complaints. Statins block cholesterol synthesis early in its metabolic pathway at a step that not only reduces cholesterol synthesis but also the production of other important metabolites including ubiquinone or coenzyme Q10, dolichols and other prenylated isoprenoids required for normal functioning of the skeletal myocyte (Fig. 1). Consequently, most

The management of statin myopathy

The management of statin myopathy includes preventing symptoms in the first place, monitoring patients with symptoms or CK elevations, using novel strategies to lower lipids in statin intolerant patients, and constantly evaluating the risk and benefits of these agents in individual patients (Box 3).

Muscle complaints and frank rhabdomyolysis generally increase with increasing statin doses so that patients should be treated with the lowest dose necessary to achieve their therapeutic goal.

Summary

Statins are extremely well tolerated, but approximately 10% of patients in clinical practice experience some form of muscle-related side effects. These can range from asymptomatic CK elevation, to muscle pain, weakness, and its most severe form, rhabdomyolysis. Higher-risk patients for statin myopathy are those older than 80, with a small body frame, on higher statin doses, on other medications, or with other systemic diseases including hepatic or renal diseases, diabetes mellitus, or

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    No funding was received for this report.

    Carmelo V. Venero, MD, is a Cardiovascular Disease Fellow at the University of Tennessee Medical Center Knoxville, Tennessee. Paul D. Thompson received research support from Merck/Pfizer/Astra Zenica/B.Braun; is a consultant for Astra Zenica/Merck; is on the Speaker's Bureau for Merck/Pfizer/Abbott/AstraZenica/ScheringPlough; is a stock shareholder of Schering Plough/Merck/Illumina/Zoll; and receives occasional speaking honoraria from Merck/Pfizer/Abbott/AstraZenica/ScheringPlough.

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