Implementation of CYP2C19 Genotyping to Guide Antiplatelet Therapy

Dual antiplatelet therapy with aspirin and a P2Y12 receptor inhibitor represents the standard
of care treatment for the prevention of major adverse cardiovascular events in patients
undergoing percutaneous coronary intervention (PCI). Currently, 3 oral P2Y12 receptor
inhibitors (clopidogrel, prasugrel, and ticagrelor) are available for clinical use.
Clopidogrel remains the most broadly used P2Y12 receptor inhibitor. However, it is well
established that clopidogrel-induced antiplatelet effects is suboptimal in many patients who
are thus exposed to an increased risk of adverse cardiovascular events. Studies have shown
that genotypes of the cytochrome P450 (CYP) 2C19 enzyme, which is a key determinant of
clopidogrel metabolism, contribute to these findings. In fact, clopidogrel is a prodrug that
requires bioactivation by the CYP2C19 enzyme. Approximately 30-40% of individuals have the
loss-of-function (LOF) CYP2C19 genotype and cannot sufficiently convert clopidogrel to its
active form, thereby gaining little to no benefit from the drug. Prasugrel and ticagrelor are
alternative agents whose effectiveness is not dependent on CYP2C19 genotype. A boxed warning
on the Food and Drug Administration (FDA)-approved clopidogrel labeling warns of reduced
effectiveness in patients with the LOF genotype and recommends alternative therapies in these
patients. Guidelines from the Clinical Pharmacogenetics Implementation Consortium (CPIC)
specifically recommend prasugrel or ticagrelor over clopidogrel for patients with a LOF
CYP2C19 genotype who undergo PCI. In turn, these recommendations have led to the use in
clinical practice of genetic testing of CYP2C19 genotypes as an aid to clinicians in
determining therapeutic strategies for patients undergoing PCI. However, the uptake of
genetic testing in real-world clinical practice has been limited by the availability of
assays able to provide genetic results in a timely fashion. The availability of an assay
recently approved by the FDA, SpartanRX, which provides results within one-hour facilitates
performing genetic testing as a clinical test in real-world practice. We therefore propose to
1) examine the feasibility of implementing CYP2C19 genotyping using SpartanRX as standard of
care for patients undergoing cardiac catheterization at UF Health Jacksonville providing the
opportunity for clinicians to embrace genotype-guided antiplatelet therapy in those who
proceed to PCI and 2) determine if CYP2C19 genotype-guided antiplatelet therapy reduces the
risk for major adverse cardiovascular outcomes after PCI.

Inclusion Criteria:

- Age ≥18 years

- Undergoing left heart catheterization for signs and symptoms suggestive for CAD

Exclusion Criteria:

- Inability to provide written informed consent.