This is an overview of an article entitled “Clinical Outcomes and Sustainability of Using CYP2C19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention”, published in the April 2018 issue of Circulation: Genomic and Precision Medicine.
This is an overview of an article entitled clinical outcomes and sustainability of using cyp2c19 genotype guided antiplatelet therapy after percutaneous coronary intervention published in the april 2018 issue of circulation genomic and precision medicine clopidogrel is the most widely prescribed p2y 12 inhibitor following percutaneous coronary intervention or pci
To prevent platelet aggregation and reduce the risk of major adverse cardiovascular events including stent – thrombosis clopidogrel is a pro drug that requires bio transformation by cytochrome p450 or cyp enzymes most notably cyp2c19 to generate its active metabolite here’s a visual representation of the metabolism of clopidogrel yielding an active metabolite via
The action of cyp2c19 and an active metabolite via an alternative pathway cyp2c19 loss of function or lof variants are common in the population pharmacokinetic and pharmacodynamic studies show that loss of function variants are associated with lower active metabolite levels and a diminished antiplatelet response multiple retrospective analyses have demonstrated a
Significantly higher risk for major adverse cardiovascular or cerebrovascular events after pci and clopidogrel treated patients carrying one cyp2c19 loss of function allele also known as intermediate metabolizers or ims or two loss of function alleles also known as poor metabolizers or pms compared to capita girl treated patients without a loss of function allele
Given the lack of prospective clinical outcome data there remains considerable debate and uncertainty surrounding whether clinical cyp2c19 genetic testing should be routinely used to guide antiplatelet therapy selection and pci patients an increasing number of institutions are implementing cyp2c19 genetic testing however the data are limited on the feasibility
Sustainability and clinical impact of using a cyp2c19 genotyping strategy to guide p2y 12 inhibitor selection following pci in real-world clinical settings as opposed to expensive rigorous randomized clinical trials with strict inclusion and exclusion criteria that might not reflect real-world practice in 2012 the university of north carolina implemented an
Algorithm incorporating cyp2c19 genotyping an antiplatelet therapy selection in high-risk patients defined as having an acute coronary syndrome or high-risk coronary anatomy cyp2c19 genotype testing was ordered at the interventional cardiologists discretion and then performed clinically on-site using pcr based methods which reported the presence of the cyp2c19 star
2 and star 3 loss of function variants within 24 to 48 hours in the paper under discussion the author’s saw to one determine the frequency of cyp2c19 testing and use of alternative p2y 12 inhibitor therapy such as prasugrel or take a girl or in cyp2c19 intermediate metabolizers and poor metabolizers over time to identify the factors that influence the cyp2c19
Testing and p2y twelve inhibitor selection and three examined the relationship between p2y twelve inhibitor cyp2c19 status and clinical outcomes this single center observational cohort included one thousand one hundred and ninety three consecutive adults who underwent pci data was manually abstracted from the electronic health record this figure shows the study
Population by cyp2c19 genotype and the antiplatelet agents prescribed of the 1193 patients who underwent pci 868 or 73% were genotyped 30% of the tested patients carried one or two loss of function alleles and were more likely to be prescribed press grow or tyke a girl or the authors also examined factors that led to this selection of procedural or tyke a girl
Or following pci clinical factors including an acute coronary syndrome or acs indication for pci left anterior descending or led artery stent and press agra or tyco a griller use upon admission were also significantly associated with press agra or tyco a girl or selection after pci whereas elevated bleeding risk and clopidogrel use on admission or significantly
Associated with clopidogrel selection after pci the authors then determined whether the cyp2c19 status modified the association between certain clinical factors an antiplatelet therapy selection in the graph on the left they showed that the association between acs indication for pci and press a girl or tyka girl or selection was not modified by cyp2c19 status
But as shown in the middle graph the association between elevated bleeding risk and a lower likelihood of prescribing press a girl or tyke a girl or was more pronounced than patients without a cyp2c19 loss of function allele compared to aiims and pms the interaction p-value was 0.023 in the graph on the right the association between led artery stent placement and
Procedural or tyka girl or selection was only evident in patients without a loss of function allele with an interaction p-value of 0.009 clinical outcomes were evaluated in 999 patients with follow-up available after the index pci the graph on the left demonstrates that cyp2c19 loss-of-function variants carriers treated with clopidogrel exhibited a significantly
Higher risk more than three-fold increase in risk of major adverse cardiovascular or cerebrovascular events compared to loss of function variants carriers treated with alternative therapy compared the red and black lines in contrast no significant difference in major adverse cardiovascular or cerebrovascular events was observed in patients without cyp2c19 loss
Of function variants treated with clopidogrel relative to alternative therapy compared the green and blue lines the middle graph shows that there was no difference in the risk of developing a clinically significant bleeding event across the cyp2c19 variant and antiplatelet therapy groups the graph on the right shows that in patients with an acs indication for
Their index pci the risk of adverse events was highest in the cyp2c19 loss-of-function variants treated with clopidogrel the red line consistent with the overall study population the frequency of cyp2c19 testing and use of alternative therapy in loss-of-function variants carriers varied significantly throughout the study period the graph on the left shows that
Following a very high rate of genotyping during the initial six months 88% the proportion genotyped decreased during the subsequent 12 months 61 percent to 65 percent and then increased the 78 percent during the final six months the graph on the right shows the frequency of tyka girl or or prasugrel prescribing the frequent use of alternative therapy and cyp2c19
Loss-of-function variants carriers shown with the red bars during the initial six months eighty-three percent was sustained during the subsequent six-month period but declined to 54 percent before increasing to 68 percent during the final six months use of alternative therapy and patients without loss of function variants shown with the blue bars was much lower
What are the clinical implications of this study first clinical implementation of cyp2c19 genotyping to guide antiplatelet therapy followed pci is feasible in a real world setting cyp2c19 testing was frequently ordered and used to guide p2y 12 inhibitor therapy second consistent with previously published observational studies this study found that clopidogrel
Use in cyp2c19 loss-of-function variants was associated with a higher risk of major adverse cardiac and cerebrovascular events with more than three times the risk third the use of cyp2c19 testing waned over the time frame of the study implying that sustaining this type of intervention and clinical care can be challenging finally this study illustrates the need
For the development of new strategies aimed at sustaining genotype guided prescribing interventions over time
Transcribed from video
CYP2C19-Guided Antiplatelet Therapy After PCI By Circulation an American Heart Association Journal