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
Highlights
The CYP2C19 nonfunctional genotype reduces clopidogrel effectiveness after percutaneous coronary intervention (PCI)
We report on physician uptake of CYP2C19 testing, genotype results and turnaround time, and both acute and chronic antiplatelet therapy prescribed after genotype results were available
We further show that the availability of a rapid and user-friendly genotyping platform led to high adoption of CYP2C19 testing for patients presenting to the cardiac catheterization laboratory with intent for PCI
Summary
The CYP2C19 nonfunctional genotype reduces clopidogrel effectiveness after percutaneous coronary intervention (PCI). Three oral P2Y12 receptor antagonists (clopidogrel, prasugrel, and ticagrelor) are clinically available. Prasugrel and ticagrelor have an indication only for the treatment of patients with acute coronary syndrome (ACS), while clopidogrel is the only oral P 2Y12 receptor antagonist with an indication for the treatment of stable CAD [5]. In patients undergoing PCI, studies have consistently shown that those with reduced clopidogrel-induced antiplatelet effects, who persist with high on-clopidogrel platelet reactivity, are at high risk for ischemic recurrences, including stent thrombosis [8,9,10,11]. Emerging studies have shown that the presence of enhanced clopidogrel-induced antiplatelet effects, leading to low platelet reactivity, may increase the risk of bleeding complications [9]. Polymorphisms in the CYP2C19 gene have consistently shown to have a role [12,13,14]
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