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Center for Pharmacogenomics and Individualized Therapy, Centers, Divisions, Faculty, Featured, General, Pharmacotherapy and Experimental Therapeutics, Research, Craig Lee
Grayson Mendenhall
November 15, 2016



pci
After a coronary artery stent is inserted, patients are given clopridogrel to prevent blood clots. (Image courtesy of the University of Florida)

Researchers at the University of North Carolina at Chapel Hill have found that a quick, precise genetic test can significantly reduce the risk of cardiovascular events by helping to identify a more effective medication for some heart patients who receive a stent.

The test identifies a genetic deficiency that affects the body’s ability to activate clopidogrel, a common anti-clotting drug given after a coronary artery stent is inserted. During a recent multi-institutional study from NIH’s Implementing Genomics in Practice Network, researchers at UNC, University of Florida Health and other sites throughout the country analyzed medical outcomes in 1,815 patients who had genetic testing at the time of their cardiac procedure. The genetic testing allows physicians to pinpoint the best anti-clotting medication for each patient.

The study reported significant results: About 60 percent of patients with the genetic 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 found. Their findings were presented Nov. 15 at the American Heart Association’s Scientific Sessions in New Orleans and published in JACC Cardiovascular Interventions.

The study examined the effect of genotype-guided treatment on cardiovascular outcomes after a heart procedure known as percutaneous coronary intervention, or PCI, in which a metallic stent is inserted into a heart artery to treat a blockage. More broadly, one UNC-Chapel Hill researcher said it shows the power and the promise of personalized medicine, which tailors medical decisions based on a patient’s genetic information and other unique characteristics.

“Patients with the genetic deficiency saw significantly better outcomes when treated with an alternative drug,” said Craig Lee, Pharm.D., Ph.D., associate professor in the Division of Pharmacotherapy and Experimental Therapeutics in the UNC Eshelman School of Pharmacy and a co-author of the study. “For this study, we used data from real-world patients for whom genetic testing was used to guide their therapy.”

plavix
About 30 percent of patients have an impaired ability to activate clopidogrel, which increases their risk for stroke, heart attacks and death. (Image courtesy of the University of Florida)

About 30 percent of all patients have a genetic deficiency that impairs their ability to activate the clopidogrel, which can lead to decreased effectiveness and increased risk for adverse cardiovascular events such as strokes, heart attacks and death. Having timely access to a patient’s genetic information can be particularly helpful as physicians work to prescribe the most appropriate medicine.

“This is an important breakthrough in personalized medicine because it shows how a genetic marker can be used to modify treatments and improve patient outcomes,” said Tim Wiltshire, Ph.D., director of the UNC Center for Pharmacogenomics and Individualized Therapy.

In addition to pinpointing the best drug for PCI patients, the genetic testing is efficient. On average during the study, a patient’s genetic information was available in about one day and an alternative medication was provided within a similar time.

“There was prompt genotyping, and the patients were quickly given the drug we thought would work best for them,” said Larisa Cavallari, Pharm. D., director of the Center for Pharmacogenomics at the University of Florida College of Pharmacy and lead author of the current study.

Yet decoding a patient’s genetic tendencies isn’t just about rapid treatment: Many patients take an anti-clotting drug for a year or longer. Patients who had the genetic deficiency and received an alternative medication were less likely to have a major adverse cardiovascular event compared with those who received clopidogrel during the follow-up period of up to a year, researchers found.

The findings are the first from a large group of U.S. patients to show that the risk of cardiovascular problems is reduced when PCI patients with a genetic deficiency get an alternative medication, Lee said.

Craig Lee
Craig Lee, Pharm.D., Ph.D.

“This should give providers confidence to use more effective, alternative medications in their patients who carry this genetic variant” Lee said.

The genetic test that identifies a patient’s response to clopidogrel is already being used at UNC Hospitals and Clinics in Chapel Hill. Patient samples are analyzed by the UNC Health Care Molecular Pathology and Genetics Lab, which helps to expedite results. In most cases, test results are available within a day. That helps physicians working closely with clinical pharmacists decide in a timely manner which drug to prescribe, said George “Rick” Stouffer, III, M.D., the Henry A. Foscue Distinguished Professor of Medicine and chief of cardiology at UNC.

The findings being presented today are encouraging, said Stouffer who is a co-author of the current study. The results of pending clinical trials may help to determine whether or not the genotyping for clopidogrel response becomes more widely used in cardiac care, Stouffer said. However, clinical trial data may not be available for several years. In the meantime, Lee said data such as these from patients genotyped as part of clinical care support broader implementation.

The present research was organized through a collaborative genomic medicine network funded by the National Institutes of Health and known as Implementing Genomics in Practice. The UNC Center for Pharmacogenomics and Individualized Therapy is an affiliate member of this network. Other institutions that participated in the clopidogrel research were the University of Florida, the University of Maryland-Baltimore, the University of Pittsburgh, the University of Alabama-Birmingham, Vanderbilt University Medical Center, the University of Illinois-Chicago, Indiana University-Indianapolis, Sanford Health, Duke University and the University of Pennsylvania.

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