Statins & Myopathy

• Statins are considered very effective in reducing cardiovascular morbidity and mortality in high-risk patients. However, although adherence to statins improves morbidity and mortality , it remains suboptimal. 
• One of the most important causes of nonadherence is the so-called statin intolerance, mainly because of muscle-related symptoms.

Myopathy

• Myopathy is defined in various ways.
•  The National Lipid Association (NLA) defines myopathy as symptoms of myalgia in addition to an elevation in serum creatine kinase (CK) greater than 10 times the upper limit of normal (CK >10 × ULN).
• The American College of Cardiology (ACC), American Heart Association (AHA), and National Heart, Lung, and Blood Institute (NHLBI) use myopathy as a general term referring to any disease of the muscles, which is the most common definition.

Mechanism

• Precise mechanisms underlying statin-associated myopathy are not well understood; however, theories do exist. Proposed mechanism  includes: 

1. Alterations in myocyte membrane cholesterol.
2. Depletion of isoprenoids that control myofiber apoptosis
3. Depletion of ubiquinone or coenzyme Q10 (CoQ₁₀)  

Clinical Feature

• Typically present as proximal, symmetric muscle weakness and/or soreness
•  Muscle tenderness and there may be functional impairments such as difficulty raising the arms above the head, arising from a seated position, or climbing stairs; these symptoms are often described as fatigue or tiredness by the patient
• Less often the discomfort is asymmetric.
• Other symptoms may include unintentional weight loss, tachycardia, nausea, and brown urine from myoglobin breakdown.

Time to Onset of Symptoms

• Within weeks to months after the initiation of statin therapy but may occur at any time during treatment
• Some other reference claimed , generally  patients may tolerate statin therapy for up to 1 year before statin myopathies occur. Nevertheless, statin therapy in combination with fibrates, particularly gemfibrozil, may induce reactions in a little over 30 days.
• Normally myalgias and weakness resolve and serum creatine kinase concentrations return to normal over days to weeks after discontinuation of the drug. 

 Evaluation of Patient that Develops Myalgia

• CK level should be measured to rule out rhabdomyolysis (CK levels >10 times the upper limit of normal values or elevation of serum creatinine levels), which mandates immediate stopping of the statin and prompt hydration.
• Assess the presence of contributing factors, such as lifestyle modification, concomitant medication, hypothyroidism and vitamin D deficiency) .

 Proposed evaluation for statin associated myopathy

References: 

1. (Bitzur et al., 2013)Bitzur, R., Cohen, H., Kamari, Y., Harats, D., Shalev, V., Chodick, G., … Spezzi, A. (2013). Intolerance to statins: mechanisms and management. Diabetes Care, 36 Suppl 2(Supplement 2), S325–30. http://doi.org/10.2337/dcS13-2038
2. http://www.medscape.com/viewarticle/759844_5                                   
3. www.uptodate.com.