The following are key points to remember from an American Heart Association scientific statement on CYP2C19 genetic testing for P2Y12 inhibitor therapy:

1. There is significant variability in the efficacy and safety of oral P2Y12 inhibitors, which are used to prevent ischemic outcomes in common diseases such as coronary and peripheral arterial disease and stroke.
2. Clopidogrel, a prodrug, is the most used oral P2Y12 inhibitor and is activated primarily after being metabolized by a highly polymorphic hepatic cytochrome CYP2C219 enzyme.
3. Loss-of-function genetic variants in CYP2C219 are common, can result in decreased active metabolite levels and increased on-treatment platelet aggregation, and are associated with increased ischemic events on clopidogrel therapy. Such patients can be identified by CYP2C19 genetic testing and can be treated with alternative therapy.
4. Conversely, universal use of potent oral P2Y12 inhibitors such as ticagrelor or prasugrel, which are not dependent on CYP2C19 for activation, has been recommended but can result in increased bleeding.
5. Recent clinical trials and meta-analyses have suggested that a precision medicine approach in which loss-of-function carriers are prescribed ticagrelor or prasugrel and noncarriers are prescribed clopidogrel may reduce ischemic events without increasing bleeding risk.
6. The evidence appears to support CYP2C19 genetic testing before oral P2Y12 inhibitors are prescribed in patients with acute coronary syndromes (ACS) or percutaneous coronary intervention (PCI).
7. Clinical implementation of such genetic testing will depend on multiple factors: rapid availability of results or adoption of the concept of performing preemptive genetic testing, provision of easy-to-understand results with therapeutic recommendations, and seamless integration in the electronic health record.
8. The 2016 American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions guideline on dual antiplatelet therapy (DAPT) in coronary artery disease (CAD) does not recommend the routine use of genetic testing.
9. The 2017 European Society of Cardiology focused update on DAPT in CAD similarly does not recommend routine genetic testing except in specific situations such as for patients with recurrent adverse events if the results of testing may change therapy.
10. Given the pharmacokinetic, pharmacodynamic, clinical trial data (with mixed results) and recent meta-analyses findings, CYP2C19 genetic testing before prescription of clopidogrel or ticagrelor/prasugrel in patients with ACS or PCI may be beneficial but needs more real-world high-quality validation data.

Clinical Topics: Prevention, Stable Ischemic Heart Disease

Keywords: Genetic Testing, Receptors, Purinergic P2Y12

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