Statin induced myopathy overview

# Overview
Statin induced myopathy is a common entity that presents as a spectrum of symptoms ranging from complete absence of symptoms to myalgia, myositis and rhabdomyolysis. Myopathy, which is a general term that describes any pathology of the muscle, occurs in around 10 to 15% of patients taking statins. The pathophysiology of statin induced myopathy is complex. As for the treatment, it is guided by the severity of the symptoms and the degree of increase in creatine kinase levels.
N-of-1 trials have examined this:
- StatinWISE
- TaSINI
- Wood

# Classification
Statin induced myopathy is a spectrum of muscular problems caused by the intake of statins. Myopathy is, by definition, any pathology of the muscle. The spectrum of statin induced myopathy can be classified into: myalgia, asymptomatic increase in creatine kinase, myositis and rhabdomyolysis. Myalgia is defined as one or combination of symptoms of muscle weakness, tenderness or pain in the context of normal or minimally elevated creatinine kinase. Myositis is defined as the presence of symptoms of muscle weakness, tenderness or pain in the setting of an elevated creatine kinase up to ten folds the normal level. Rhabdomyolysis is a potentially lethal acute degeneration of the skeletal muscle.

# Pathophysiology
Statin induced myopathy has a complex poorly understood multifactorial pathophysiology. It is postulated that statin induced myopathy is caused by apoptosis of the skeletal muscle cells due to disrupted intracellular calcium signaling and mitochondrial dysfunction secondary to the depletion of mevalonate metabolism products, particularly coenzyme Q10.

# Epidemiology
The prevalence of statin induced myopathy, described as a spectrum of clinical conditions ranging from myalgia to myositis and rhabdomyolysis, is almost 10-15%.

# Risk Factors
Several risk factors predispose to statin induced myopathy. Some of the intrinsic risk factors are advanced age, genetic predisposition, diabetes, hypertension, hypothyroidism and renal diseases. Other extrinsic factors play a role in statin induced myopathy, including alcohol consumption, vitamin D deficiency, excessive exercise, trauma or concomitant use of other drugs like fibrates, mainly gemfibrosil, protease inhibitors and macrolide antibiotics.

# Screening
Screening by measuring the creatine kinase level is not recommended by the national lipid association for statin induced myopathy unless the patient has significant predisposing factors like renal diseases, thyroid problems, metabolic diseases or pre-existing muscular diseases.

# Differential Diagnosis
Myalgia is a common complaint and should not be attributed directly to the use of statins. The patient should be evaluated for any thyroid problems, inflammatory processes, alcohol use, excessive exercise, electrolyte disturbances, side effects of other medications or vitamin deficiencies.

# Diagnosis

# History and Symptoms
The symptoms of statin induced myopathy belong to a spectrum ranging from being mild and asymptomatic to severe and lethal. The time of onset of symptoms varies among people, but the median time of onset of symptoms is four weeks since the beginning of the treatment. Similarly, the time for the resolution of symptoms after appropriate management also varies among individuals.The history of the patient should provide a description of the characteristics of the muscle pain as well as details about medications, history of trauma, exercise or excessive alcohol use.

# Laboratory Tests
When a patient presents with symptoms suggestive of statin induced myopathy, the diagnostic evaluation should include measuring the level of creatine kinase. It is useful to obtain the levels of TSH, ESR and vitamin D levels as well in order to rule out other diseases that can cause myalgia.

# Treatment
When symptoms of myopathy or elevation of creatine kinase occur in the setting of a patient taking statins, the majority of patients may safely continue the treatment with statins. The decision on whether the patient can discontinue or continue statins depends on two factors: the severity of the symptoms and the severity of the increase in the creatine kinase level. Statins can be safely continued when the symptoms are tolerable and the creatine kinase is elevated less than 5 times the upper limits of normal. Otherwise, if the creatine kinase level is higher than five times the upper limit of normal or if the symptoms are intolerable regardless of the level of creatine kinase, statins should be stopped for a certain period of time and restarted again with lower doses or with different types of statins. The role of vitamin D and coenzyme Q10 is still controversial in the management of statin induced myopathy as no studies support their use yet.