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Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysis Bare metal versus drug eluting stents for ST-segment elevation myocardial infarction in the TOTAL trial Randomized Comparison of Everolimus- and Zotarolimus-Eluting Coronary Stents With Biolimus-Eluting Stents in All-Comer Patients Percutaneous coronary intervention reduces mortality in myocardial infarction patients with comorbidities: Implications for elderly patients with diabetes or kidney disease Remote ischaemic conditioning and healthcare system delay in patients with ST-segment elevation myocardial infarction Targeting the Immune System in Atherosclerosis: JACC State-of-the-Art Review Outcomes of off- and on-hours admission in ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention: A retrospective observational cohort study Obesity, Diabetes, and Acute Coronary Syndrome: Differences Between Asians and Whites Coronary Catheterization and Percutaneous Coronary Intervention in China: 10-Year Results From the China PEACE-Retrospective CathPCI Study Prevention, Diagnosis, and Management of Radiation-Associated Cardiac Disease: JACC Scientific Expert Panel
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Review Article12 (4), e007811

JOURNAL：Circulation. Article Link

Clopidogrel Pharmacogenetics: State-of-the-Art Review and the TAILOR-PCI Study

NL Pereira, CS Rihal, DYF So et al. Keywords: clinical trial; clopidogrel; cytochrome P450 CYP2C19; drug labeling; genetics; humans; pharmacogenetics

ABSTRACT

Common genetic variation in CYP2C19 (cytochrome P450, family 2, subfamily C, polypeptide 19) *2 and *3 alleles leads to a loss of functional protein, and carriers of these loss-of-function alleles when treated with clopidogrel have significantly reduced clopidogrel active metabolite levels and high on-treatment platelet reactivity resulting in increased risk of major adverse cardiovascular events, especially after percutaneous coronary intervention. The Food and Drug Administration has issued a black box warning advising practitioners to consider alternative treatment in CYP2C19 poor metabolizers who might receive clopidogrel and to identify such patients by genotyping. However, routine clinical use of genotyping for CYP2C19 loss-of-function alleles in patients undergoing percutaneous coronary intervention is not recommended by clinical guidelines because of lack of prospective evidence. To address this critical gap, TAILOR-PCI (Tailored Antiplatelet Initiation to Lessen Outcomes due to Decreased Clopidogrel Response After Percutaneous Coronary Intervention) is a large, pragmatic, randomized trial comparing point-of-care genotype-guided antiplatelet therapy with routine care to determine whether identifying CYP2C19 loss-of-function allele patients prospectively and prescribing alternative antiplatelet therapy is beneficial.

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