Effect of CYP2C19 Genotype on Ischemic Outcomes During Oral P2Y12 Inhibitor Therapy

Pereira, Naveen L.; Rihal, Charanjit S.; Lennon, Ryan J.; Marcus, Gil; Shrivastava, Sanskriti; Bell, Malcolm R.; So, Derek; Geller, Nancy L.; Goodman, Shaun G.; Hasan, Ahmed; Lerman, Amir; Rosenberg, Yves; Bailey, Kent R.; Murad, Mohammad Hassan; Farkouh, Michael E.

doi:10.1016/j.jcin.2021.01.024

Cited by 124 publications

(104 citation statements)

References 41 publications

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“…The subanalysis of POPular Genetics showed that treatment with clopidogrel led to a lower number of bleeding events compared with ticagrelor (adjusted HR, 0.74; 95% CI, 0.56-0.96). 11 However, a meta-analysis involving 18,808 patients from randomized clinical trials and observational studies 28 showed that ticagrelor and prasugrel did not increase bleeding risk compared with clopidogrel, both in CYP2C19 LOF carriers (relative risk, 0.97; 95% CI, 0.68-1.40) and noncarriers (relative risk, 0.99; 95% CI, 0.86-1.13). Our study confirmed that the two P2Y12 inhibitors were safe with low bleeding risks.…”

Section: Discussionmentioning

confidence: 99%

Clopidogrel versus Ticagrelor in CYP2C19 Loss-of-Function Allele Noncarriers: A Real-World Study in China

Zhang

Shi

et al. 2021

Thromb Haemost

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Objective This article compares the clinical outcomes of clopidogrel and ticagrelor in patients with acute coronary syndrome (ACS) without cytochrome P450 (CYP)2C19 loss-of-function (LOF) alleles and investigates whether clopidogrel could be an alternative P2Y12 inhibitor without increasing the risk of ischemic events. Methods Patients were divided into the clopidogrel-treated group and the ticagrelor-treated group. Inverse probability of treatment weighting (IPTW) calculated by propensity scores was used to adjust confounding covariates. The primary outcome was major adverse cardiovascular or cerebrovascular events (MACCEs) within 12 months. The secondary outcomes were MACCEs plus unstable angina, and clinically significant bleeding events. Results Finally, 2,199 patients were included. Of them, 1,606 were treated with clopidogrel, and 593 were treated with ticagrelor. The mean age of the original cohort was 59.92 ± 9.81 years. During the 12-month follow-up period, MACCEs occurred in 89 patients (4.0%). No significant differences were observed in MACCEs (IPTW-adjusted hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.65–1.18), MACCEs plus unstable angina (IPTW-adjusted HR, 1.20; 95% CI, 0.91–1.59), or clinically significant bleeding events (IPTW-adjusted HR, 0.81; 95% CI, 0.53–1.23) between the clopidogrel- and ticagrelor-treated groups. Conclusion In patients with ACS without CYP2C19 LOF alleles, clopidogrel was not associated with a higher risk of MACCEs when compared with ticagrelor. The main findings of this study support use of clopidogrel in CYP2C19 LOF noncarriers as an alternative P2Y12 inhibitor, which may reduce medical expenses and adverse reactions caused by more potent P2Y12 inhibitors in these patients.

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Section: Discussionmentioning

confidence: 99%

Clopidogrel versus Ticagrelor in CYP2C19 Loss-of-Function Allele Noncarriers: A Real-World Study in China

Zhang

Shi

et al. 2021

Thromb Haemost

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“…The trial also showed a significant reduction in prespecified sensitivity analyses of cumulative events and a post hoc analysis of events at 90 days in favor on genotype‐guided therapy ( P = 0.001). A meta‐analysis of genotype‐guided antiplatelet RCTs has recently been published 74 . The reduction of ischemic events in patients with coronary artery disease who predominantly underwent PCI by ticagrelor or prasugrel, in comparison with clopidogrel, was based primarily on the presence of CYP2C19 loss‐of‐function carrier status 74 …”

Section: Different Perspectives On Pharmacogenetic Evidencementioning

confidence: 99%

Moving Pharmacogenetics Into Practice: It’s All About the Evidence!

Luzum

Petry

Taylor

et al. 2021

Clin Pharma and Therapeutics

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The evidence for pharmacogenetics has grown rapidly in recent decades. However, the strength of evidence required for the clinical implementation of pharmacogenetics is highly debated. Therefore, the purpose of this review is to summarize different perspectives on the evidence required for the clinical implementation of pharmacogenetics. First, we present two patient cases that demonstrate how knowledge of pharmacogenetic evidence affected their care. Then we summarize resources that curate pharmacogenetic evidence, types of evidence (with an emphasis on randomized controlled trials [RCT]) and their limitations, and different perspectives from implementers, clinicians, and patients. We compare pharmacogenetics to a historical example (i.e., the evidence required for the clinical implementation of pharmacokinetics/therapeutic drug monitoring), and we provide future perspectives on the evidence for pharmacogenetic panels and the need for more education in addition to evidence. Although there are differences in the interpretation of pharmacogenetic evidence across resources, efforts for standardization are underway. Survey data illustrate the value of pharmacogenetic testing from the patient perspective, with their providers seen as key to ensuring maximum benefit from test results. However, clinicians and practice guidelines from medical societies often rely on RCT data to guide treatment decisions, which are not always feasible or ethical in pharmacogenetics. Thus, recognition of other types of evidence to support pharmacogenetic implementation is needed. Among pharmacogenetic implementers, consistent evidence of pharmacogenetic associations is deemed most critical. Ultimately, moving pharmacogenetics into practice will require consideration of multiple stakeholder perspectives, keeping particularly attuned to the voice of the ultimate stakeholder—the patient.

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“…Seven of these were randomized controlled trials. 66 There were nearly 16,000 patients across the included studies. 66 The analysis found that genotyping for CYP2C19 was warranted when considering the use of oral P2Y12 inhibitor therapy to differentiate the use of clopidogrel and other agents.…”

Section: Clinical Guidelines/recent Trialmentioning

confidence: 99%

“…66 There were nearly 16,000 patients across the included studies. 66 The analysis found that genotyping for CYP2C19 was warranted when considering the use of oral P2Y12 inhibitor therapy to differentiate the use of clopidogrel and other agents. 66 The CPIC clopidogrel-CYP2C19 guideline was last updated in 2013 and the DPWG guidelines prior to that year.…”

Section: Clinical Guidelines/recent Trialmentioning

confidence: 99%

“…66 The analysis found that genotyping for CYP2C19 was warranted when considering the use of oral P2Y12 inhibitor therapy to differentiate the use of clopidogrel and other agents. 66 The CPIC clopidogrel-CYP2C19 guideline was last updated in 2013 and the DPWG guidelines prior to that year. Currently, CPIC is updating the clopidogrel-CYP2C19 guideline again to include information from the Tailor-PCI trial as well as other up-to-date information beyond the 2013 publication.…”

Section: Clinical Guidelines/recent Trialmentioning

confidence: 99%

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Pharmacogenomics in the United States Community Pharmacy Setting: The Clopidogrel-CYP2C19 Example

Kisor

Petry

Bright

2021

PGPM

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Pharmacogenomics (PGx) is expanding across health-care practice settings, including the community pharmacy. In the United States, models of implementation of PGx in the community pharmacy have described independent services and those layered on to medication therapy management. The drug-gene pair of clopidogrel-CYP2C19 has been a focus of implementation of PGx in community pharmacy and serves as an example of the evolution of the application of drug-gene interaction information to help optimize drug therapy. Expanded information related to this drug-gene pair has been provided by the US Food and Drug Administration and clinical PGx guidelines have and continue to be updated to support clinical decision-making. Most recently direct-to-consumer (DTC) PGx has resulted in patient generated sample collection and submission to a genetic testing-related company for analysis, with reporting of genotype and related phenotype information directly to the patient without a health-care professional guiding or even being involved in the process. The DTC testing approach needs to be considered in the development or modification of PGx service models in the community pharmacy setting. The example of clopidogrel-CYP2C19 is discussed and current models of PGx implementation in the community pharmacy in the United States are presented. New approaches to PGx services are offered as implementation continues to evolve and may now include DTC information.

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Effect of CYP2C19 Genotype on Ischemic Outcomes During Oral P2Y12 Inhibitor Therapy

Cited by 124 publications

References 41 publications

Clopidogrel versus Ticagrelor in CYP2C19 Loss-of-Function Allele Noncarriers: A Real-World Study in China

Clopidogrel versus Ticagrelor in CYP2C19 Loss-of-Function Allele Noncarriers: A Real-World Study in China

Moving Pharmacogenetics Into Practice: It’s All About the Evidence!

Pharmacogenomics in the United States Community Pharmacy Setting: The Clopidogrel-CYP2C19 Example

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