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PREDICT helps pinpoint right statin for patient

Oct. 4, 2012, 9:44 AM

When O.T. Hayes, 67, of Lebanon, Tenn., first starting seeing his cardiologist, David Hansen, M.D., for treatment of his coronary artery disease, it was hard to predict which of the various medications available would help control Haynes’ high cholesterol.

A number of powerful cholesterol-lowering medications, known as statins, have come on the market in the last dozen years or so, and Hansen prescribed several for Haynes, trying to find one that achieved his cholesterol goal without causing debilitating side effects.

David Hansen, M.D.

“There was a full house of drugs that were tried on him: simvastatin, atorvastatin, fluvastatin and rosuvastatin,” said Hansen, associate professor of Medicine. “That is four different statins, and each time he reported back that his muscles started aching and he felt weak.”

Haynes had to stop those medications because it is well known that statin lipid-lowering drugs can cause muscle pain and weakness, and if one is not careful about stopping at the first sign of that, it can lead to the breakdown of skeletal muscle and the release of cellular components from muscle that travel to kidneys and cause acute renal failure, Hansen said.

Then, the PREDICT test became available. Vanderbilt began using PREDICT (Pharmacogenomic Resource for Enhanced Decisions in Care and Treatment) last year to test patients for a genetic variation that would increase the chances that simvastatin, one of the most widely prescribed drugs in the United States, would cause muscle aches.

“If you have two copies of a variant of the SLC01B1 gene, you’re at an almost twenty fold increased risk of muscle toxicity,” says Dan Roden, M.D., assistant vice chancellor for Personalized Medicine and the William Stokes Professor of Experimental Therapeutics.

Last year, Vanderbilt became the first academic medical center to offer testing for the gene variant. As part of its personalized medicine initiative, any Vanderbilt provider attempting to prescribe simvastatin at the 40 mg dose receives a prompt, directing them to consider a lower dose of a more potent statin if the patient carries an abnormal copy of the SLC01B1 gene.

“I ordered testing for him, and it turns out Mr. Haynes received one defective copy of the SLC01B1 gene from his parents, and the other gene is what we’d call normal. That puts people at intermediate myopathy risk for having side effects from simvastatin,” Hansen said.

Simvastatin, and most other statins, use the same metabolic pathway as a way of being broken down into smaller bits and being excreted from the body. Based on this information, Vanderbilt was able to publish the first international gene-based dosing guideline for statins earlier this year.

“The clinical community has been waiting for this type of guidance for several years,” said Russ Wilke, M.D., director of Genomics and Cardiovascular Risk at Vanderbilt, and lead author of the guideline.

“Mr. Haynes probably accumulated an excessive amount of drug in his body because he was not taking it up into his liver correctly. Because of that buildup, he was at risk for developing complications from statin therapy,” Hansen said.

“We switched him to lovastatin, and he just returned to clinic and reported he can take it because he isn’t having the same complications,” Hansen said. In addition, his LDL level has reached its target goal.

“This patient had a lot of trial and error over a four-year period prior to the availability of the PREDICT test,” Hansen said. “I was an early adopter of the PREDICT test, and when it first came out, I started using it. As a practicing cardiologist, a very good percentage of my patients have had the PREDICT test. It expands what I know about each of my patients.”

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