Routine CYP2C19 Genotyping to Adjust Thienopyridine Treatment After Primary PCI for STEMI

Hulot, Jean‐Sébastien; Cayla, Guillaume; Khalife, Khalifé; Tafflet, Muriel; Montalescot, Gilles; Breton, Hervé; Teíger, Emmanuel; Dambrin, Grégoire; Schmutz, Laurent; Funck, F; Berthier, Romain; Piot, Christophe; Hannebicque, G.; Lognoné, Thérèse; Poli, F. De; Chevalier, Bernard; Lhoest, Nicolas; Schneeberger, Michel; Delarche, Nicolas; Faure, Antoine; Aelion, Hélène; Godin, Matthieu; Gilard, Martine; Ritz, Bernard; Barraud, Pascal; Barnay, Pierre; Saidi, Lyassine Nait; Dref, Olivier Le; Garot, Philippe; Rangé, Gregoire; Georges, Jean-Louis; Robin, Christophe; Cottin, Yves; Belle, Loïc; Souteyrand, Géraud; Lafont, A.; Fournier, Anne; Dupouy, Patrick; Shayne, J.; Chapon, Philippe; Boureux, C; Faure, Jean‐Pierre; Amer, Hakim Ben; Furber, Alain; Ormezzano, Olivier; Bayet, Gilles; Karrillon, G.; Maillard, Luc; Grenzinger, A.; Avran, Alexandre; Köning, René; Dumant, D.; Lamit, X; Dauphin, R.; Drogoul, Laurent; Cuisset, Thomas; Wittenberg, Olivier; Peyre, Jean-Pascal; Laury, P.; Robert, Raphaël

doi:10.1016/j.jcin.2020.01.219

Cited by 33 publications

(23 citation statements)

References 35 publications

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“…The data from real-world observations 43 demonstrated a higher risk for cardiovascular events in patients with a CYP2C19 LOF allele who received clopidogrel than in those who received an alternative therapy. The GIANT (NCT01134380) study 44 showed a similar outcome, and thus it was vital to verify the potential benefit of the genotype-guided personalized test. To date, four meta-analyses on genotype-guided antiplatelet therapy versus conventional antiplatelet treatment have been conducted, [18][19][20][21] yielding different conclusions.…”

Section: The Conclusion Was Not Based Solely On High-quality Evidencementioning

confidence: 99%

Genotype‐guided antiplatelet treatment versus conventional therapy: A systematic review and meta‐analysis

Zhang

Xiang

Liu

et al. 2020

Brit J Clinical Pharma

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This meta-analysis was carried out to explore if a personalized antiplatelet strategy based on genotyping is superior to conventional therapy.Methods: PubMed, Web of Science, EMBASE and the Cochrane Library were searched from the inception of each database to 5 May 2020. Studies reporting endpoints in genotype-guided treatment group and conventional treatment group were included. The endpoint results were presented as the risk ratio (RR), with 95% confidence interval (CI).Results: A total of 10 561 patients from 16 studies (eight randomized controlled trials [RCT] and eight cohort studies) were included in the meta-analysis. The rates of major adverse cardiovascular events (MACE), stent thrombosis and myocardial infarction (MI) were significantly lower in the genotype-guided group than in the conventional treatment group (RR 0.56, 95% CI 0.44-0.73, P < .0001; RR 0.40, 95% CI 0.24-0.67, P = .0005; RR 0.45, 95% CI 0.35-0.58, P < .00001, respectively).A significant difference was found between the two groups in major bleeding (RR 0.73, 95% CI 0.55-0.98, P = .04), which was not robust after sensitivity analysis. Conclusion:Genotype-guided antiplatelet treatment could decrease the risk of MACE, stent thrombosis and MI in patients with coronary artery disease or undergoing percutaneous coronary intervention, without increasing the risk of bleeding over a long follow-up period. The decreased risk of efficacy outcomes was more obvious in cohort studies. Well-organized RCTs and clinical trials are required to verify the benefit of genotype-guided therapy.

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Section: The Conclusion Was Not Based Solely On High-quality Evidencementioning

confidence: 99%

Genotype‐guided antiplatelet treatment versus conventional therapy: A systematic review and meta‐analysis

Zhang

Xiang

Liu

et al. 2020

Brit J Clinical Pharma

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show abstract

“…Examples of alternative approaches to evidence generation include pragmatic trials and observational studies of patients receiving testing as part of clinical care. Similar to RCTs, many pragmatic and observational studies to date have demonstrated improved outcomes with a pharmacogenetic‐guided approach 50–55 . Data from additional pragmatic trials are forthcoming from efforts, such as from the Implementing GeNomics In pracTicE (IGNITE) Pragmatic Trials Network (ClinicalTrials.gov Identifier: NCT04445792) and the Ubiquitous Pharmacogenomics Consortium 4 .…”

Section: Types Of Pharmacogenetic Evidence and Their Limitationsmentioning

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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“…Because of CYP2C19 genetic polymorphism, the response of clopidogrel differs widely among patients. Previous studies showed that adjusting thienopyridine treatment in patients after primary percutaneous coronary intervention for ST-Elevation Myocardial Infarction, according to the CYP2C19 genotype, can improve a patient's outcome [31,32]. Whether adjusting the clopidogrel dose after CYP2C19 genotyping in stroke patients can reduce recurrent stroke risk needs further investigation.…”

Section: Plos Onementioning

confidence: 99%

Efficacy of aspirin, clopidogrel, and ticlopidine in stroke prevention: A population-based case-cohort study in Taiwan

et al. 2020

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Background In real-world practice settings, there is insufficient evidence on the efficacy of antiplatelet drugs, including clopidogrel, aspirin, and ticlopidine, in stroke prevention. Purpose To compare the efficacies between aspirin and clopidogrel and aspirin and ticlopidine in stroke prevention. Methods This population-based case-cohort study utilized the data obtained from a randomized sample of one million subjects in the Taiwan National Health Insurance Research Database. Patients who were hospitalized owing to the primary diagnosis of ischemic stroke from January 1, 2000 to December 31, 2010 and treated with aspirin, ticlopidine, or clopidogrel were included in the study. Propensity score matching with a 1:4 ratio was performed to compare aspirin with ticlopidine and clopidogrel. The criteria for inclusion were the use of one of the three antiplatelet drugs for more than 14 days within the first month after the stroke and then continued use of the antiplatelet drugs until the study endpoint of recurrent stroke. Results During the 3-year follow-up period, the recurrent stroke rates were 1.62% (42/2585), 1.48% (3/203), and 2.55% (8/314) in the aspirin, ticlopidine, and clopidogrel groups, respectively. Compared with the patients treated with aspirin, those treated with clopidogrel and ticlopidine showed competing risk-adjusted hazard ratios of recurrent stroke of 2.27 (1.02–5.07) and 0.62 (0.08–4.86), respectively. Conclusion Compared with the patients treated with aspirin, those treated with clopidogrel were at a higher risk of recurrent stroke. For stroke prevention, aspirin was superior to clopidogrel whereas ticlopidine was not inferior to aspirin.

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Routine CYP2C19 Genotyping to Adjust Thienopyridine Treatment After Primary PCI for STEMI

Abstract: @DrHulot_PARCC Anti-platelet therapy adjustment guided by CYP2C19 genotyping can be done in <7 days in STEMI patients with saliva DNA analysis.

Cited by 33 publications

References 35 publications

Genotype‐guided antiplatelet treatment versus conventional therapy: A systematic review and meta‐analysis

Genotype‐guided antiplatelet treatment versus conventional therapy: A systematic review and meta‐analysis

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

Efficacy of aspirin, clopidogrel, and ticlopidine in stroke prevention: A population-based case-cohort study in Taiwan

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