October 13, 2011

Statins included in next phase of PREDICT initiative

Statins included in next phase of PREDICT initiative

Simvastatin, the generic form of the statin Zocor, is one of the most widely prescribed drugs in the United States. The drug is effective in reducing LDL-cholesterol levels and lowering the risk for heart attacks and strokes.

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.

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.

“If you have two copies of the SLC01B1 gene, you’re at an almost 20-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.

Vanderbilt providers currently receive an electronic reminder cautioning them against the use of 80 mg simvastatin, based on a recent U.S. Food and Drug Administration (FDA) warning about increased risk of muscle damage.

Dan Roden, M.D.

Dan Roden, M.D.

Russell Wilke, M.D.

Russell Wilke, M.D.

“Since the great majority of practices do not have access to pharmacogenomic testing to identify patients at highest risk for muscle damage, the FDA has uniformly cautioned against the use of high-dose simvastatin,” said Russell Wilke, M.D., associate professor of Medicine in Clinical Pharmacology.

In a few weeks, Vanderbilt will be the first academic medical center to offer testing for the gene variant. As part of its personalized medicine initiative, PREDICT, any Vanderbilt provider attempting to prescribe simvastatin at the 40 mg dose will also receive a prompt, this time directing them to consider a lower dose of a more potent statin if the patient carries an abnormal copy of the SLC01B1 gene.

“PREDICT allows providers to tailor drug therapy based on an individual’s unique genetic makeup so patients will be more likely to receive the right drug, at the right dose, the first time,” Wilke said.

Vanderbilt began using PREDICT (Pharmacogenomic Resource for Enhanced Decisions in Care and Treatment) last year to test cardiac cath lab patients for a genetic variation that would render the drug clopidogrel less effective.

More than 3,000 patients have been tested, and so far, more than 600 patients have been found to have one or two copies of a genetic variant that makes them “poor responders” to clopidogrel and many have been switched to another drug.

This latest phase of PREDICT will roll out in the adult primary care and cardiology clinics.

A prognostic model looks through each patient’s electronic medical record searching for indications that he or she will eventually need to be on a statin (based on age, gender, race, body weight and co-morbidities).

A mathematical algorithm assigns patients a ‘score’ based on the statistical likelihood of their being prescribed a statin within the next three years.

The information is then entered into the patient’s electronic medical record, and if a provider attempts to order simvastatin, he or she will receive notification that the patient is at high risk for developing clinically meaningful side effects while on the drug.

Not every side effect can be avoided, of course.

“We’re just reducing the odds,” Roden says. “That’s what applying genetics at the bedside is all about. It expands what you know about the individual patient.”