Aug. 28, 2024
Performing genetic-guided testing before prescribing blood thinner drugs for patients with acute coronary syndrome or percutaneous coronary intervention can be helpful.
The American Heart Association's scientific statement published in Circulation offers guidance for the use of CYP2C19 genetic testing when prescribing oral P2Y12 inhibitor therapy. The blood thinner drugs help prevent blood clots, which can lead to heart attacks and strokes.
CYP2C19 genetic-guided testing allows for tailoring the choice of blood thinners to a patient's genetic variants. Benefits of prescribing the right drug to the right patient:
- Less toxicity.
- Cost-effective.
- Greater efficiency.
"There's a lot of published data about performing genetic testing specifically for the CYP2C19 enzyme to guide which antiplatelet drug patients should take after a heart attack or stroke, or after having coronary stenting or angioplasty procedures," says Naveen L. Pereira, M.D., a cardiologist at Mayo Clinic in Rochester, Minnesota, and chair of the group that issued the statement. "This statement summarizes the data. We felt that providing useful information would help clinicians determine what to do with genetic testing in this patient population."
"Earlier clinical trial research showed that genetic testing in reducing ischemic events for patients was of borderline statistical significance, likely due to limited power of these studies," says Dr. Pereira. "Incorporating these and other studies shows that patients could benefit from genetic-guided therapy. The totality of evidence — drug metabolism studies, observational studies, clinical trials and recent meta-analyses that combine all the data — point to the fact that genetic testing could be beneficial to the patient. It moves the needle in terms of reducing ischemic events, such as strokes, heart attacks or repeat procedures. But importantly, it could decrease bleeding if we use the precision medicine approach based on genetic testing."
Ineffective blood thinners?
Oral P2Y12 inhibitors are used for patients with coronary artery disease, peripheral arterial disease and stroke. Clopidogrel is the most common prescribed antiplatelet therapy.
Certain genetic variation in the CYP2C19 gene can affect how well some patients metabolize clopidogrel. The genetic variation is linked to the loss of enzymatic function and therefore decreased active clopidogrel metabolite levels. It may vary in different ethnic and racial groups. Up to 30% of patients may not be able to metabolize and activate clopidogrel, putting them at a higher risk of a stroke or heart attack.
Alternative medications
Identifying patients who metabolize clopidogrel poorly and treating them with alternative medications can lead to fewer ischemic events.
Such CYP2C19 loss-of-function (LOF) carriers have significantly reduced cumulative blockage of blood clotting or ischemic events when treated with the oral P2Y12 inhibitor drugs ticagrelor or prasugrel rather than clopidogrel. Ticagrelor and prasugrel are not dependent on CYP2C19 for activation.
However, ticagrelor and prasugrel are more potent than clopidogrel in comparison, and if used universally, they can cause increased bleeding complications. A CYP2C19 genetic-guided testing precision medicine approach allows for LOF carriers to take ticagrelor or prasugrel, and for noncarriers to take clopidogrel, which overall can reduce bleeding events without compromising efficacy in reducing ischemic events.
What's next?
Moving forward, more research is needed. "The landscape of how to provide an antiplatelet drug therapy for these patients is rapidly changing," says Dr. Pereira. "It's not just doing genetic testing; it's also determining the appropriate duration of therapy and whether to use these drugs or P2Y12 inhibitors with or without aspirin with genetic guidance. It will be important to do a clinical trial showing what is beneficial."
For more information
Pereira NL, et al. CYP2C19 Genetic Testing for Oral P2Y12 Inhibitor Therapy: A Scientific Statement From the American Heart Association. Circulation. 2024;150:e129.
Refer a patient to Mayo Clinic.