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

Abstract

BackgroundThe 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.MethodsPatients 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.ResultsIn 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).ConclusionThese 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

Frequency and clinical outcomes of CYP2C19 genotype-guided escalation and de-escalation of antiplatelet therapy in a real-world clinical setting

“…CYP2C19 genotyping has been successfully implemented into clinical practice at a number of institutions. 22,27,[31][32][33] Given the historical use of clopidogrel as first-line therapy, early genotype-guided strategies and recommendations focused on escalation of IM/PMs to alternative therapy. 3,22 In our study, approximately one-half of IM/PMs initiated on clopidogrel were escalated to alternative therapy in accordance with the genotype-guided algorithm.…”

<p><em>CYP2C19*17</em> May Increase the Risk of Death Among Patients with an Acute Coronary Syndrome and Non-Valvular Atrial Fibrillation Who Receive Clopidogrel and Rivaroxaban</p>

“…5 A genotypebased antiplatelet therapy, as observed in a number of observational and randomized trials, is capable of overcoming high residual platelet reactivity [6][7][8][9] and may lead towards a decrease in the number of adverse cardiovascular events. [8][9][10][11][12][13][14][15][16] These results are proven by the results of a metaanalysis of 9000 patients on clopidogrel: the carriership of low function allelic variants increases the risk of major adverse cardiovascular events (MACE) 1.5-fold and the risk of stent thrombosis 2.8-fold. 17 The negative results of later meta-analyses can be explained by the heterogeneity of the population and inclusion in the meta-analyses of patients with a stable coronary disease.…”

Clinical Utility of Pharmacogene Panel‐Based Testing in Patients Undergoing Percutaneous Coronary Intervention

“…12 Testing was expanded to UF Health in Jacksonville in 2016, which also focused on patients undergoing LHC with intent for PCI. 13 For the purpose of this study, we included 211 patients (mean age 65 ± 11 years) who were genotyped for CYP2C19, underwent PCI, and consented to storage of their excess blood samples for DNA biobanking and future research 14 (Figure 1).…”