Genetic Testing Could Help Clinicians Prescribe Blood Thinners

Genetic testing can help providers identify the appropriate anti-platelet drugs for patients, leading to enhanced efficacy and fewer side effects, according to a study published in JACC: Cardiovascular Interventions.

Providers typically prescribe anti-platelet drugs to prevent complications from blood clotting after a procedure to open clogged arteries. These patients can use one of the various anti-platelet medications, such as clopidogrel, ticagrelor, or prasugrel.

Clinicians usually prescribe patients with coronary artery disease clopidogrel to reduce the risk of ischemic events, including blood clots, stroke, heart attack, recurrent chest pain, and death following a percutaneous coronary intervention or stent placement.

For the study, researchers compared people who were treated with the newer anti-platelet agents ticagrelor or prasugrel, as opposed to clopidogrel. The team evaluated data about the effect of the CYP2C19 gene on ischemic events in nearly 16,000 people.

The meta-analysis sourced more than 1,000 research studies, including several randomized clinical trials. One of the trials was TAILOR-PCI, a large study funded by the Mayo Center for Individualized Medicine and the National Heart, Lung, and Blood Institute (NHLBI).

The results showed that genetic variants in CYP2C19 can cause the loss of its function. These variants interfere with the body’s ability to metabolize and activate clopidogrel, meaning patients with these variants would benefit from the other anti-platelet medications.

"Our results suggest that clopidogrel can safely be given to approximately 70 percent of patients with coronary artery disease following percutaneous coronary intervention. 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," said Naveen Pereira, MD, a Mayo Clinic cardiologist, and first and corresponding author of the paper.

“But these data show a 30 percent 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."

Researchers noted that point-of-care genetic testing is available and can be used by personnel who are not laboratory-trained. This testing has more than 99 percent accuracy in identifying the genetic makeup of patients to guide such treatment. The test is inexpensive and can be administered at the bedside via an oral swab. Results are available 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," said Richard Weinshilboum, MD, a pharmacologist and director of Mayo Clinic's Center for Individualized Medicine.

It’s useful for providers to know that they can safely and effectively treat most patients with clopidogrel. This knowledge has practical benefits as well: Clopidogrel is less costly, accepted by most insurance companies, and carries fewer side effects like shortness of breath and bleeding.

The study shows a clear advantage of genetic testing in helping providers choose the right anti-platelet drug, helping enhance efficacy and avoid side effects. The team stated that their findings could reveal new approaches for anti-platelet prescribing.

"This meta-analysis confirms the impact of a pharmacogenomics approach to tailoring anti-platelet therapy in the treatment of coronary artery disease," said Michael Farkouh, MD, 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."