Statin Induced Myopathy
Clinical Features And Risk Factors
Clinical trials have always revealed the development of myalgia with statin use as a side effect. Approximately 1.5 million people experience a muscle related side effect whilst taking a statin. This review will discuss statin induced myopathy from recent epidemiological studies and Randomised Controlled Trials. (RCT).
The term myopathy is used to include the entire spectrum of muscle related adverse events. This includes myalgia, myositis, rhabdomyolysis and an asymptomatic increase in the concentration of creatinine kinase.
Symptoms of statin use include muscle pain, muscle tenderness, fatigue, tendon pain and nocturnal cramping. The muscle symptoms seem to be worse with exercise.
In a small retrospective study of 45 patients, the mean duration of statin therapy before onset of symptoms was 6.3 months (range 1 week to 4 years). In this study the mean duration of myalgia after stopping statin therapy was 2.3 months (range 1 week to 4 months). Muscle symptoms that develop in a patient who has been taking statins for several years are unlikely to have been caused by these drugs.
The mechanism of statin induced myopathy is unknown. However there are many proposed mechanisms. One of these is the impaired synthesis of cholesterol. This leads to changes in the cholesterol in the myocyte membranes changing the behaviour of the membrane. Another proposed mechanism is impaired synthesis of compounds in the cholesterol pathway, in particular deficiency of co enzyme Q10-which could lead to impaired enzyme activity in the mitochondria. A third proposed mechanism is depletion of isoprenoids which are lipids that are products of the hydroxymethylglutaryl coenzyme A reductase pathway and this prevents myofibre apoptosis.
Evidence from randomised controlled trials show that myopathy correlates closely with dose of statins and is independent of reductions in low density lipoprotein cholesterol.
There is no clear data available about the relative risks associated with individual factors, since the dose, and the possibility of the type of statin affects the risk of precipitating myopathy.
Risk factors such as advanced age, female sex, low body mass index, diminished hepatic and renal function, multiple co-morbidities or medications, excess alcohol, intercurrent infections, surgery or trauma, drug interactions and dietary effects have been largely derived from clinical trials and through reporting of adverse effects.
Factors that increase the serum concentration of a statin have the potential to increase the risk of myopathy. This would mean, factors that affect the pharmacokinetics of statins, leading to increased concentrations of drugs in blood or tissue may predispose to myopathy.
Although evidence shows a link between increasing serum statin concentration and muscle complaint, no direct link has been shown between intramuscular statin concentrations and myopathy.
Pharmacodynamic factors such as transporters affecting the bioavailability of statins, are probably important in determining toxicity.
Drug responses can also be affected by predisposing genetic factors. No definitive evidence has been found that statins are harmful in patients with pre existing non metabolic myopathy.
One study proposed that statins exacerbated exercise induced injury of skeletal muscles, but without tissue evidence from a muscle biopsy, this conclusion is debatable.
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