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Vanderbilt to Begin Genetic Testing to Predict Risk of Severe Muscle Toxicity with Simvastatin

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Vanderbilt University said last week that it will begin testing for gene variants associated with severe muscle toxicity in patients treated with the generic cholesterol-lowering drug simvastatin.

The university said that it will be "the first academic medical center to offer testing for the gene variant" in SLC01B1, which has been linked to muscle toxicity in a small percentage of patients who receive high doses of the drug.

Genetic testing will be offered as part of Vanderbilt's Pharmacogenomic Resource for Enhanced Decisions in Care and Treatment, or PREDICT, initiative. Under the program, any university-affiliated physician prescribing simvastatin at doses of 40 mg or higher will receive an electronic prompt directing them "to consider a lower dose of a more potent statin if the patient carries an abnormal copy of the SLC01B1 gene," the university said.

Vanderbilt launched the PREDICT program last year to test cardiac cath lab patients for CYP2C19 gene variants, which reduces their ability to metabolize the antiplatelet drug Plavix and may put them at heightened risk for blood clots following stent procedures (PGx Reporter 10/6/2010). According to the university, more than 3,000 patients have been genetically tested under that program so far. Of those, more than 600 patients had one or two copies of a CYP2C19 variant that rendered them “poor responders” to Plavix.

The university said it will introduce SLC01B1 testing within its adult primary care and cardiology clinics "in a few weeks."

Simvastatin, which was marketed by Merck as Zocor before it went generic, is a widely used drug for lowering LDL-cholesterol, which in turn can lower risk of heart-related illnesses. While it was still a brand-name drug, Zocor was among the top-selling statins.

"However, growing evidence indicates that at a dose of 80 milligrams a day, about 2 percent of patients will experience severe muscle toxicity – muscle aches accompanied by biochemical evidence of muscle damage," Vanderbilt said in a statement. "The risk for developing this complication, which in extreme cases can cause kidney damage and even death, is increased when patients carry a single genetic variation."

People who carry two copies of the SLC01B1 gene have a 20-fold increase in the risk of muscle toxicity when treated with simvastatin, according to Dan Roden, Vanderbilt's assistant vice chancellor for personalized medicine.

Given the varying levels of access to pharmacogenetic testing across medical centers, the US Food and Drug Administration has issued a broad warning against the increased risk of muscle damage with simvastatin use at 80 mg. In line with this recommendation, Vanderbilt providers currently receive an electronic reminder cautioning them against the use of simvastatin at this dose.

Genetic testing for SLCO1B1 variants through the PREDICT program will now allow Vanderbilt providers to more accurately tailor treatment for those more likely to experience adverse reactions with simvastatin.

Vanderbilit's prognostic model scans each patient’s electronic medical record for indicators based on age, gender, race, body weight, and co-morbidities that suggest they might be prescribed a statin in the next three years. Based on a probabilistic score derived from this information, physicians who attempt to prescribe simvastatin will receive a warning that the patient may be at increased risk for a serious side effect.

"We’re just reducing the odds," Roden said in a statement. "That’s what applying genetics at the bedside is all about. It expands what you know about the individual patient."

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