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

• DOI: 10.1186/s12967-018-1469-8
• Publication Date: 2018-04-11T12:38:14Z
• Authors: Larisa H. Cavallari; Francesco Franchi; Fabiana Rollini; Latonya Been; Andrea Rivas; Malhar Agarwal; D. Max Smith; Kimberly Newsom; Yan Gong; Amanda R. Elsey; Petr Starostik; Julie A. Johnson; Dominick J. Angio...
• Keywords: Male; Ticagrelor; Genotype; Genotyping Techniques; Research; R; 610; Middle Aged; Percutaneous coronary intervention; Clopidogrel; 3. Good health; Cytochrome P-450 CYP2C19; 03 medical and health sciences; Percutaneous Coronary Intervention; Phenotype; 0302 clinical medicine; Medicine; Humans; Female; CYP2C19; Prasugrel; Platelet Aggregation Inhibitors

Abstract Background 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.

Methods 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.

Results 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).

Conclusion 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