Risks Associated with Statin Therapy

Las Vegas—An estimated 71 million US adults have increased levels of low-density lipoprotein (LDC) cholesterol, and statins are widely prescribed for treatment. Substantially sized randomized, controlled trials have shown statin-associated relative risk reductions in ischemic stroke by 20%, myocardial infarction by 20% to 30%, and all-cause mortality by 10% to 15% [Ann Int Med. 2013;159:688-697]. While statins have been successful in lowering LDL cholesterol, there are also overlooked risks.

Commonly reported adverse events associated with statins are hepatotoxicity, myalgia, new-onset diabetes, and rhabdomyolysis. Other possible adverse events associated with statins include alopecia, cataracts, hemorrhagic stroke, and psychosis, though these have not been proven in studies.

Louis Kuritzky, MD, clinical assistant professor, family medicine residency program, University of Florida, led a workshop at the CRS meeting that focused on the risks of statin use.

A previous study found that statin toxicity can occur years after maintaining a stable statin regimen [Lancet. 2007;370(9601)1781-1790]. Prescribers should monitor patients for possible hepatotoxicity and potential drug–drug interactions.

Simvastatin has recently sparked concern due to an association between high doses and increased risk of myopathy. In a recent study, researchers compared simvastatin 20 mg and 80 mg doses [N Engl J Med. 2011;365(4):285-287]. Fifty-two patients (0.9%) in the 80 mg group developed myopathy, while 1 patient (0.02%) did so in the 20 mg group. Twenty-two of the patients (0.4%) in the 80 mg group developed rhabdomyolysis, and no cases were reported in the
20 mg group. Myopathy was defined as a serum creatine kinase level >10 times the upper limit of normal and unexplained muscle weakness or pain. Rhabdomyolysis was defined as unexplainable muscle pain or weakness with a serum creatine kinase level >40 times the upper limit of normal.

In 2013, simvastatin labeling changed. Now a simvastatin 80 mg dose is limited to patients who have taken simvastatin without developing myopathy for ≥12 months. If 40 mg simvastatin is inadequate, patients should stop treatment and switch to a more potent statin.

A study demonstrated that statins may increase the risk of developing diabetes in patients who are predisposed to the condition [Diabetes Obesity Metabolism. 2013: DOI 10.1111/dom.12254]. Increased statin doses were linked to new-onset diabetes. Although, for every case that statins caused the development of diabetes, there were approximately 3 cardiovascular events reduced with a high dose of statin therapy versus a moderate dose. The researchers concluded that the slight risk of developing type 2 diabetes as a result of statin therapy was outweighed by the potential to decrease cardiovascular events.

Research has also shown that statins contribute to tendinopathy. Ninety-six patients participated in a study in which they exhibited tendinitis (n=63) and tendon rupture (n=33) [Arthritis & Rheumatism. 2008;59(3):367-372]. Typically, tendinopathy occurred within the first year after the patient was prescribed a statin (59%). Tendon manifestations were identified in 5 different statins: (1) atorvastatin (n=35); (2) simvastatin (n=30); (3) pravastatin (n=21); (4) fluvastatin (n=5); and (5) rosuvastatin (n=5). The researchers mentioned that there is no evidence as to how tendon injuries are produced in patients taking statins.—Melissa D. Cooper