Clinical implementation of rapid CYP2C19 genotyping to guide antiplatelet therapy after percutaneous coronary intervention

• Published in: Journal of translational medicine Vol. 16; no. 1; p. 92
• Main Authors: Cavallari, Larisa H, Franchi, Francesco, Rollini, Fabiana, Been, Latonya, Rivas, Andrea, Agarwal, Malhar, Smith, D Max, Newsom, Kimberly, Gong, Yan, Elsey, Amanda R, Starostik, Petr, Johnson, Julie A, Angiolillo, Dominick J
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 11-04-2018; BioMed Central; BMC
• Subjects: Balloon angioplasty; Clopidogrel; Clopidogrel - pharmacology; Complications and side effects; CYP2C19; Cytochrome P-450; Cytochrome P-450 CYP2C19 - genetics; Dosage and administration; Female; Genetic aspects; Genotype; Genotyping Techniques; Humans; Male; Middle Aged; Patient outcomes; Percutaneous Coronary Intervention; Phenotype; Physiological aspects; Platelet Aggregation Inhibitors - pharmacology; Prasugrel; Ticagrelor; United States; Prasugrel; Clopidogrel; Genotype; Percutaneous coronary intervention; CYP2C19; Ticagrelor
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-018-1469-8

The CYP2C19 nonfunctional genotype reduces clopidogrel effectiveness after percutaneous coronary intervention (PCI). Following clinical implementation of CYP2C19 genotyping at University Florida (UF) Health Shands Hospital in 2012, where genotype results are available approximately 3 days after PCI, testing was expanded to UF Health Jacksonville in 2016 utilizing a rapid genotyping approach. We describe metrics with this latter implementation.
Patients at UF Health Jacksonville undergoing left heart catheterization with intent to undergo PCI were targeted for genotyping using the Spartan RX™ system. Testing metrics and provider acceptance of testing and response to genotype results were examined, as was antiplatelet therapy over the 6 months following genotyping.
In the first year, 931 patients, including 392/505 (78%) total patients undergoing PCI, were genotyped. The median genotype test turnaround time was 96 min. Genotype results were available for 388 (99%) PCI patients prior to discharge. Of 336 genotyped PCI patients alive at discharge and not enrolled in an antiplatelet therapy trial, 1/6 (17%) poor metabolizers (PMs, with two nonfunctional alleles), 38/93 (41%) intermediate metabolizers (IMs, with one nonfunctional allele), and 119/237 (50%) patients without a nonfunctional allele were prescribed clopidogrel (p = 0.110). Clopidogrel use was higher among non-ACS versus ACS patients (78.6% vs. 42.2%, p < 0.001). Six months later, among patients with follow-up data, clopidogrel was prescribed in 0/4 (0%) PMs, 33/65 (51%) IMs, and 115/182 (63%) patients without a nonfunctional allele (p = 0.008 across groups; p = 0.020 for PMs versus those without a nonfunctional allele).
These data demonstrate that rapid genotyping is clinically feasible at a high volume cardiac catheterization facility and allows informed chronic antiplatelet prescribing, with lower clopidogrel use in PMs at 6 months. Trial registration ClinicalTrials.gov Identifier: NCT02724319; registered March 31, 2016; https://www.clinicaltrials.gov/ct2/show/NCT02724319?term=angiolillo&rank=7.