Genetic testing at UMMC helps doctors identify effective medication for heart stent patients

The University of Maryland Medical Center (UMMC) is now offering a simple genetic test to patients who receive heart stents to determine whether they have a genetic deficiency that affects how they respond to a common drug to prevent blood clots. Patients are typically given the medication, clopidogrel, to prevent cardiovascular events after having a stent placed in a coronary artery to treat a blockage.

The test, which is performed by analyzing a patient's DNA, isolated from a blood sample, identifies a variation in the CYP2C19 gene that affects the body's ability to activate the drug. About 30 percent of the population has the variation and may be less responsive to the drug.

A recent study by researchers at the University of Maryland School of Medicine (UM SOM) and other sites found that this genetic testing helps doctors identify more effective medication for heart stent patients, significantly reducing the risk of subsequent cardiac events. About 60 percent of patients with this deficiency were given a different, more effective medication. Using the genetic data to guide changes in therapy reduced the percentage of deaths, heart attacks or strokes by nearly half compared with those who continued taking clopidogrel, the researchers reported in November at the American Heart Association's Scientific Sessions in New Orleans.

Initially offered at UMMC as part of the clinical study, the genetic test is now standard of care at UMMC for patients who receive a stent in a procedure known as percutaneous coronary intervention, or PCI, after having a heart attack or severe blockage. These patients are at highest risk of having another cardiovascular event.

"This is a true personalized medicine initiative," says Mark R. Vesely, MD, an associate professor of medicine at UM SOM and an interventional cardiologist at UMMC who was a co-investigator of the study. "The test provides the ability to optimize therapy for a specific patient by helping us tailor our treatment based on the patient's unique genetic profile."

"An alternative medication, ticagrelor, has been shown in other studies to be more effective to prevent future events like heart attacks. However, ticagrelor is less reliably taken by patients because it is significantly more expensive and less well-tolerated than clopidogrel," Dr. Vesely says. "The genetic test helps us determine which patients are likely to receive sufficient protection from clopidogrel and thus avoid the extra cost and side effects."

The genetic-testing program at UMMC, which began in August, is funded by the medical center and the School of Medicine. The tests are processed in the Translational Genomics Laboratory at UM SOM; results are available to patients and their doctors within 24 hours.

"Our research has shown that genotyping patients enables us to predict with some certainty which medication would be most effective to prevent future cardiovascular events," says E. Albert Reece, MD, PhD, MBA, vice president for medical affairs at the University of Maryland and the John Z. and Akiko K. Bowers Distinguished Professor and dean of the University of Maryland School of Medicine. "We're now able to use that knowledge in a clinical setting for the benefit of patients."

Researchers at UM SOM and other universities in a collaborative genomic medicine network (Implementing Genomics in Practice, or IGNITE) analyzed medical outcomes in 1,815 patients (1,224 men and 591 women) who had genetic testing when they had the PCI procedure. More than 250 of the patients were part of the UM SOM study, which enrolled patients at UMMC and the Baltimore VA Medical Center, starting in 2013.

"Our findings are significant because they confirm previous retrospective studies in real-world clinical settings," says study co-author Amber L. Beitelshees, PharmD, MPH, an assistant professor of medicine at UM SOM who specializes in pharmacogenomics. "By implementing CYP2C19 genotyping at the time of percutaneous coronary intervention, we were able to show that prescribing alternative anti-platelet therapy to patients with a CYP2C19 genetic deficiency improved outcomes."

"This is exciting because we have taken a discovery we made in healthy Amish individuals and translated it all the way to the cardiac catheterization lab," Dr. Beitelshees says, referring to a previous UM SOM study with the Old Order Amish that identified a gene variation associated with diminished clopidogrel response.

That study, led by Alan R. Shuldiner, MD, the John L. Whitehurst Endowed Professor of Medicine and director of the Program in Personalized and Genomic Medicine at UM SOM, was published in JAMA in 2009. It showed that individuals with a CYP2C19 gene variation had a reduced benefit from taking clopidogrel. Based on growing clinical evidence in his study and others, the U.S. Food and Drug Administration (FDA) issued a warning about the reduced efficacy of clopidogrel in people with the genetic variation.

"With genotype-directed therapy, we have the ability to change the 'one size fits all' approach to prescribing medication and ultimately improve the quality of care we provide to our patients. Patients want personalized and individualized medicine and we are now beginning to deliver on the promises of genomic medicine," Dr. Shuldiner says.