Taking into consideration how a person’s genes affect how he or she responds to medications can help healthcare providers tailor therapeutic interventions by prescribing the right drug for the right patient for increased efficacy and decreased risk of side effects.
In an article titled ‘Effect of CYP2C19 Genotype on Ischemic Outcomes During Oral P2Y12 Inhibitor Therapy: A Meta-Analysis’ published in the journal JACC: Cardiovascular Interventions, scientists at Mayo Clinic, University of Toronto and several other institutions, examine the effects of CYP2C19 genotype on clinical outcomes in coronary artery disease (CAD) patients who were treated with the blood thinners, ticagrelor or prasugrel versus clopidogrel.
The meta-analysis sourced more than 1,000 research studies, including seven randomized clinical trials that included TAILOR-PCI, a large study funded by the Mayo Center for Individualized Medicine and NHLBI. Most patients included in the study underwent percutaneous coronary intervention (PCI).
This study, funded in part by the National Heart, Lung and Blood Institute (NHLBI), shows a clear advantage of genetic testing in helping healthcare providers choose the appropriate blood thinner or anti-platelet drug.
Ticagrelor, prasugrel and clopidogrel are anti-platelet drugs that prevent blood clotting and are commonly prescribed after a procedure to open clogged arteries. Patients with CAD are typically prescribed clopidogrel to reduce the risk of ischemic events, such as blood clots, stroke, heart attack, recurrent chest pain and death following a PCI or surgical insertion of a stent to keep a vessel patent.
A genetic and consequential functional deficiency of CYP2C19, detectable through genetic testing reveals the body’s ability to break down and activate clopidogrel. Patients with a CYP2C19 genotype that prevents them from activating clopidogrel would benefit from the other anti-platelet medications.
As part of this meta-analysis, researchers evaluated data on the effect of the CYP2C19 genotype on ischemic events in approximately 16,000 patients who were treated with the newer anti-platelet agents ticagrelor or prasugrel, as opposed to clopidogrel.
“Our results suggest that clopidogrel can safely be given to approximately 70% of patients with coronary artery disease following percutaneous coronary intervention,” says Naveen Pereira, MD, a Mayo Clinic cardiologist, and first and corresponding author of the paper. “For patients who do not have the loss-of-function CYP2C19 genotype, there is no difference in using clopidogrel, as compared to ticagrelor or prasugrel. But these data show a 30% risk reduction in ischemic events for patients who are identified by genetic testing to have the loss-of-function CYP2C19 genotype. This information means that with the help of genetic testing, we could safely prescribe generic, well-tolerated, once-daily clopidogrel to most patients and reserve the use of the newer, more expensive drugs (ticagrelor or prasugrel) for those with the loss-of-function genetic variants.”
Testing for CYP2C19 genetic variants can by performed by personnel who are not laboratory-trained and can identify the genotype with 99% accuracy, Pereira notes. The test is inexpensive and can be administered at the bedside via an oral swab and provide a guide to personalized treatment. Results for the genetic test are processible in under an hour.
“We are pleased that our decision to fund the TAILOR-PCI study with the NHLBI several years ago will help ensure better and safer care for patients suffering from coronary artery disease and serve to illustrate the value of genomic testing in the clinic,” says Richard Weinshilboum, MD, a pharmacologist and director of Mayo Clinic’s Center for Individualized Medicine.
The knowledge that most people can be safely and effectively treated with clopidogrel is practical and useful information for health care providers. Compared to ticagrelor and prasugrel, clopidogrel costs less, is accepted by most insurance companies and is associated with fewer side effects, such as bleeding and shortness of breath.
“This meta-analysis confirms the impact of a pharmacogenomics approach to tailoring anti-platelet therapy in the treatment of coronary artery disease,” says Michael Farkouh, MD, senior author on the study, a cardiologist, and multinational clinical trials chair at the University Health Network’s Peter Munk Cardiac Centre. “We believe this work should inform the next guidelines in the field and warrant further study with other databases.”