New Study Links Statins to a Rare Autoimmune Muscle Disorder

Statins are a family of drugs used by tens of millions of patients in the U.S. to lower high blood cholesterol levels. They are prescribed to prevent adverse cardiovascular events, such as heart attacks and strokes, in patients who have known cardiovascular disease (secondary prevention) as well as in patients who have not been diagnosed with such disease (primary prevention).

Public Citizen's Health Research Group has previously cautioned against using statins for primary prevention because the risk of adverse effects generally appears to outweigh the drugs' benefits for this use.[1] Particularly, we do not recommend that healthy adults with elevated low-density lipoprotein cholesterol (sometimes called "bad cholesterol") levels — but with no diabetes or elevated blood pressure — take statins to prevent cardiovascular events.[2]

A study published in the Sept. 2018 issue of the Journal of the American Medical Association Internal Medicine (JAMA Internal Medicine) showed that statins are associated with a rare but potentially disabling autoimmune muscle disorder known as idiopathic inflammatory myositis (IIM).[3] Importantly, this rare disorder is distinct from the much more common type of muscle injury (myopathy) seen with statin use.

Statins and muscle-related adverse events

Statins work by inhibiting an enzyme that is responsible for the production of cholesterol in the body.[4] Several statins have been approved by the Food and Drug Administration (see Table below). These drugs should be used only when there has been an inadequate response to nondrug treatment measures, including exercise and dietary changes. Statins should always be used in addition to a diet restricted in saturated fat and cholesterol.

Statin-Only Drugs Available in the U.S.*

*Some statins are available in combination with other drugs.
**Designated as Do Not Use

Many patients using statins experience adverse effects, including fatigue, decreased energy and muscle injury. A 2012 survey study found that 62 percent of former statin users reported that adverse effects were the main reason for ceasing use of the medication.[5] The same study found that muscle-related adverse effects while taking statins were reported by a quarter of current statin users and 60 percent of former users.

Statin-induced muscle injury can lead to asymptomatic elevations of muscle enzymes on blood tests, muscle pain, muscle weakness or other muscle adverse effects. Uncommonly, statin-induced muscle toxicity manifests as a potentially life-threatening condition known as rhabdomyolysis (rapid muscle breakdown).[6] Severe muscle pain, tenderness and weakness are common symptoms of this disorder, as is tea-colored urine. Patients with rhabdomyolysis often develop kidney failure, which may require temporary hemodialysis (mechanical filtering of the blood).

Most cases of statin-induced muscle injury resolve upon stopping use of the drug.[7] However, a small number of patients experience persistent and severely debilitating muscle symptoms after discontinuing the drugs. Researchers have identified statins as a likely trigger of IIM, a rare group of autoimmune diseases characterized by inflammation and weakness of the muscles of the upper legs and arms, but without pain.[8],[9],[10] These diseases are caused by a patient's immune system attacking muscle tissue.[11] Patients with IIM typically require treatment with immunosuppressive drugs, such as glucocorticosteroids.[12]

The aforementioned JAMA Internal Medicine study provides the most recent evidence linking use of statins to this rare muscle disease.

JAMA Internal Medicine study[13]

A team of researchers examined data from a comprehensive registry database containing detailed health information on all adult patients from south Australia who were diagnosed with any type of inflammatory muscle disease. They identified all adults aged 40 or older who had been diagnosed with IIM by a muscle biopsy from 1990 to 2014, finding 221 such patients. The average age for those patients was 62 years, and 60 percent of them were women.

The researchers then compared the frequency of statin use by those 221 IIM patients at the time of diagnosis with that of a control group of 662 age- and sex-matched individuals who did not have IIM. The control group subjects had participated in a health survey of a representative sample of adults living in two south Australian regions. Overall, the researchers' analysis showed that the IIM patients were almost two times more likely to have used a statin drug than the control group individuals without IIM.

Although IIM is a rare disease and statin-induced IIM is even rarer, the data from the Australian study showed that the proportion of patients with this serious muscle disorder who had prior exposure to statins has increased significantly over the years. Specifically, one out of 18 patients diagnosed with IIM from 2000 to 2002 had been exposed to statins, whereas 21 of 43 patients diagnosed with IIM from 2012 to 2014 had used statins. Notably, this increase over time in the proportion of IIM cases associated with statin use correlated with an increase in the number of statin prescriptions that were dispensed in Australia over the same period.

Although this observational study alone does not establish definitively that statins cause IIM, when combined with the results of prior research, it further strengthens the link between statin use and the development of idiopathic inflammatory myositis.

What You Can Do

If you are taking a statin drug to control your cholesterol level, monitor yourself for signs and symptoms of muscle disease (including fatigue and muscle weakness or pain) Talk to your doctor immediately if any such symptoms occur. Your doctor may tell you to discontinue your statin medication or may recommend switching to another statin.

If you have persistent muscle weakness after stopping a statin, talk to your doctor about being evaluated for IIM. Your doctor may recommend a muscle biopsy to determine whether you have this disorder.

Do not use fluvastatin (LESCOL XL), pitavastatin (LIVALO, ZYPITAMAG) or rosuvastatin (CRESTOR) because they have not been shown to be as effective in reducing the risk of heart attack or stroke as other statins. In addition, rosuvastatin is associated with a higher risk of rhabdomyolysis and kidney failure compared with several other safer statins.

References

[1] Statins for primary prevention: Risks without benefits. Worst Pills, Best Pills News. June 2013. /newsletters/view/854. Accessed October 30, 2018.

[2] New cholesterol treatment guidelines recommend statins for more patients. Worst Pills, Best Pills News. November 2014. /newsletters/view/927. Accessed October 31, 2018.

[3] Caughey GE, Gabb GM, Ronson S, et al. Association of statin exposure with histologically confirmed idiopathic inflammatory myositis in an Australian population. JAMA Intern Med. 2018;178(9):1224-1229.

[4] Mohassel P, Mammen AL. Statin-associated autoimmune myopathy and anti-HMGCR autoantibodies. Muscle Nerve. 2013;48(4):477-483.

[5] Cohen JD, Brinton EA, Ito MK, et al. Understanding Statin Use in America and Gaps in Patient Education (USAGE): An internet-based survey of 10,138 current and former statin users. J Clin Lipidol. 2012;6(3): 208-215.

[6] Sathasivam S. Statin induced myotoxicity. Eur J Intern Med. 2012;23(4):317-24.

[7] Babu S, Li Y. Statin induced necrotizing autoimmune myopathy. J Neurol. Sci. 2015;351(1-2):13–17.

[8] Tiniakou E, Christopher-Stine L. Immune-mediated necrotizing myopathy associated with statins: history and recent developments. Curr Opin Rhematol. 2017:29(6):604-611.

[9] Gazeley DJ, Cronin ME. Diagnosis and treatment of the idiopathic inflammatory myopathies. Ther Adv Musculoskelet Dis. 2011 Dec; 3(6): 315–324.

[10] NIH. Idiopathic inflammatory myopathy. Genetics home reference. https://ghr.nlm.nih.gov/condition/idiopathic-inflammatory-myopathy. Accessed October 25, 2018.

[11] Tiniakou E, Christopher-Stine L. Immune-mediated necrotizing myopathy associated with statins: history and recent developments. Curr Opin Rhematol. 2017:29(6):604-611.

[12] Christopher-Stine L, Basharat P. Statin-associated immune-mediated myopathy: biology and clinical implications. Curr Opin Lipidol. 2017;28(2):186-192.

[13] Caughey GE, Gabb GM, Ronson S, et al. Association of statin exposure with histologically confirmed idiopathic inflammatory myositis in an Australian population. JAMA Intern Med. 2018;178(9):1224-1229.