Cardiologists question FDA recommendations on genetic testing before taking Plavix

Which antiplatelet medication is best after a coronary stent? The costly and potential life-or-death question lingers after most of the 600,000 angioplasties performed every year in the United States. The answer may lie in your genes, but professional cardiovascular societies and many working cardiologists question the U.S. Food and Drug Administration's recent recommendation that patients undergo genetic testing before taking Plavix (clopidogrel bisulfate).

MULTIMEDIA ALERT: Sound bites of an interview with Dr. Pereira, study principal investigator, are available on the Mayo Clinic News Network.

The Tailored Antiplatelet Therapy to Lessen Outcomes after Percutaneous Coronary Intervention (TAILOR-PCI) Study, launched this summer by the Center for Individualized Medicine and the Division of Cardiovascular Diseases at Mayo Clinic, examines whether prescribing heart medication based on a patient's CYP2C19 genotype will help prevent heart attack, stroke, unstable angina, and cardiovascular death in patients who undergo percutaneous coronary intervention, commonly called angioplasty.

"The current standard of care after angioplasty is to prescribe clopidogrel for one year, regardless of a person's individual genotype, even though we have known for several years that variation in the CYP2C19 gene may diminish the benefit from the drug," says Naveen Pereira, M.D., a Mayo Clinic cardiologist and principal investigator of TAILOR-PCI. "What we don't know -- and why there is such confusion in the cardiovascular community -- is how these genetic changes affect long-term clinical outcomes and whether we can decrease overall health care costs."

Antiplatelet medication reduces the risk of heart attack, unstable angina, stroke and cardiovascular death after stent placement by reducing the possibility of blood clots around the surgical site.

Plavix, however, remains ineffective until the liver enzyme CYP2C19 metabolizes the drug into its active form. Some alternative medications, including Brilinta (ticagrelor), do not require activation through the same genetic pathway.

"Ticagrelor has its own risks, including serious or life-threatening bleeding. Additionally, this alternative therapy costs approximately six to eight times as much and must be taken twice a day," says Dr. Pereira. "Ultimately, what we're trying to do with TAILOR is use pharmacogenomics to determine whether choosing medication based on individual genotype will help patients live longer and whether the benefits will outweigh the risks of alternative therapies."

Nilay Shah, Ph.D., a Mayo Clinic Health Sciences Research professor, will study potential cost impacts to the health care system.

"This study examines as much as an $8 billion question in health care," says Dr. Shah. "Clopidogrel is the second-most prescribed medication in the United States; and although ticagrelor costs much more, the costs of taking patients into the emergency room and performing a second angioplasty are much higher."

Another additional benefit of the study will be creation of a coronary artery disease biobank containing DNA samples from the study's 5,300 participants. Researchers at Mayo Clinic and elsewhere can mine these samples and use genomic sequencing technologies to help further medicine's understanding of the origins of and risk factors for coronary heart disease.

Gianrico Farrugia, M.D., director of the Center for Individualized Medicine, says, "TAILOR-PCI is exactly the type of research we do every day -- the kind that translates into better health for our patients and improves the delivery of care for millions of patients around the world."

Heart disease is the No. 1 killer of men and women in the United States, and up to one-third of patients currently taking Plavix (up to half of some Asian populations) have a genomic variant implicated in diminished drug response. Study teams at 15 hospitals in three countries have teamed up to enroll 5,300 patients into TAILOR-PCI and deliver results in three years. The Pharmacogenomics Program in the Center for Individualized Medicine administers this study.

The participating sites are:

In the United States
* Mayo Clinic, Rochester, Minn.
* Mayo Clinic, Scottsdale, Ariz.
* Mayo Clinic, Jacksonville, Fla.
* Mayo Clinic Health System, La Crosse, Wis.
* Mayo Clinic Health System, Mankato, Minn.
* NorthShore University HealthSystem, Evanston, Ill.
* Lenox Hill Hospital, New York
* NCH Healthcare System, Naples, Fla.

In Ontario Canada
* St. Michael's Hospital, Toronto
* Toronto General Hospital, Toronto
* Sunnybrook Health Sciences Centre, Toronto
* University of Ottawa, Ottawa

In South Korea
* Konyang University Hospital, Daejeon
* Chonnam National University Hwasun Hospital, Gwangju
* Chung-Ang University, Seoul

Source: Mayo Clinic