Browsing by Author "Kelemen, Mark D."

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    Multisite Investigation of Outcomes With Implementation of CYP2C19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention
    (Elsevier, 2018-01-22) Cavallari, Larisa H.; Lee, Craig R.; Beitelshees, Amber L.; Cooper-DeHoff, Rhonda M.; Duarte, Julio D.; Voora, Deepak; Kimmel, Stephen E.; McDonough, Caitrin W.; Gong, Yan; Dave, Chintan V.; Pratt, Victoria M.; Alestock, Tameka D.; Anderson, R. David; Alsip, Jorge; Ardati, Amer K.; Brott, Brigitta C.; Brown, Lawrence; Chumnumwat, Supatat; Clare-Salzler, Michael J.; Coons, James C.; Denny, Joshua C.; Dillon, Chrisly; Elsey, Amanda R.; Hamadeh, Issam; Harada, Shuko; Hillegass, William B.; Hines, Lindsay; Horenstein, Richard B.; Howell, Lucius A.; Jeng, Linda J.B.; Kelemen, Mark D.; Lee, Y.M.; Magvanjav, Oyunbileg; Montasser, May; Nelson, David R.; Nutescu, Edith A.; Nwaba, Devon C.; Pakyz, Ruth E.; Palmer, Kathleen; Peterson, Josh F.; Pollin, Toni I.; Quinn, Alison H.; Robinson, Shawn W.; Schub, Jamie; Skaar, Todd C.; Smith, Donald M.; Sriramoju, Vindhya B.; Starostik, Petr; Stys, Tomasz P.; Stevenson, James M.; Varunok, Nicholas; Vesely, Mark R.; Wake, Dyson T.; Weck, Karen E.; Weitzel, Kristin W.; Wilke, Russell A.; Willig, James; Zhao, Richard Y.; Kreutz, Rolf P.; Stouffer, George A.; Empey, Philip E.; Limdi, Nita A.; Shuldiner, Alan R.; Winterstein, Almut G.; Johnson, Julie A.; Medical and Molecular Genetics, School of Medicine
    OBJECTIVES: This multicenter pragmatic investigation assessed outcomes following clinical implementation of CYP2C19 genotype-guided antiplatelet therapy after percutaneous coronary intervention (PCI). BACKGROUND: CYP2C19 loss-of-function alleles impair clopidogrel effectiveness after PCI. METHODS: After clinical genotyping, each institution recommended alternative antiplatelet therapy (prasugrel, ticagrelor) in PCI patients with a loss-of-function allele. Major adverse cardiovascular events (defined as myocardial infarction, stroke, or death) within 12 months of PCI were compared between patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy. Risk was also compared between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy. Cox regression was performed, adjusting for group differences with inverse probability of treatment weights. RESULTS: Among 1,815 patients, 572 (31.5%) had a loss-of-function allele. The risk for major adverse cardiovascular events was significantly higher in patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy (23.4 vs. 8.7 per 100 patient-years; adjusted hazard ratio: 2.26; 95% confidence interval: 1.18 to 4.32; p = 0.013). Similar results were observed among 1,210 patients with acute coronary syndromes at the time of PCI (adjusted hazard ratio: 2.87; 95% confidence interval: 1.35 to 6.09; p = 0.013). There was no difference in major adverse cardiovascular events between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy (adjusted hazard ratio: 1.14; 95% confidence interval: 0.69 to 1.88; p = 0.60). CONCLUSIONS: These data from real-world observations demonstrate a higher risk for cardiovascular events in patients with a CYP2C19 loss-of-function allele if clopidogrel versus alternative therapy is prescribed. A future randomized study of genotype-guided antiplatelet therapy may be of value.