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Comparison of Stent Expansion Guided by Optical Coherence Tomography Versus Intravascular Ultrasound: The ILUMIEN II Study (Observational Study of Optical Coherence Tomography [OCT] in Patients Undergoing Fractional Flow Reserve [FFR] and Percutaneous Coronary Intervention) Managing Multivessel Coronary Artery Disease in Patients With ST-Elevation Myocardial Infarction: A Comprehensive Review National assessment of early β-blocker therapy in patients with acute myocardial infarction in China, 2001-2011: The China Patient-centered Evaluative Assessment of Cardiac Events (PEACE)-Retrospective AMI Study Outcome of patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention during on- versus off-hours (a Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction [HORIZONS-AMI] trial substudy) Long-Term Outcomes in Women and Men Following Percutaneous Coronary Intervention Association of All-Cause and Cardiovascular Mortality With High Levels of Physical Activity and Concurrent Coronary Artery Calcification Clinical Significance of Concordance or Discordance Between Fractional Flow Reserve and Coronary Flow Reserve for Coronary Physiological Indices, Microvascular Resistance, and Prognosis After Elective Percutaneous Coronary Intervention Combining IVUS and Optical Coherence Tomography for More Accurate Coronary Cap Thickness Quantification and Stress/Strain Calculations: A Patient-Specific Three-Dimensional Fluid-Structure Interaction Modeling Approach Association Between Diastolic Dysfunction and Health Status Outcomes in Patients Undergoing Transcatheter Aortic Valve Replacement Cardiovascular Disease in Chronic Kidney Disease: Pathophysiological Insights and Therapeutic Options

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.