• Larisa H Cavallari, Craig R Lee, Amber L Beitelshees, Rhonda M Cooper-DeHoff, Julio D Duarte, Deepak Voora, Stephen E Kimmel, Caitrin W McDonough, Yan Gong, Chintan V Dave, Victoria M Pratt, Tameka D Alestock, R David Anderson, Jorge Alsip, Amer K Ardati, Brigitta C Brott, Lawrence Brown, Supatat Chumnumwat, Michael J Clare-Salzler, James C Coons, Joshua C Denny, Chrisly Dillon, Amanda R Elsey, Issam S Hamadeh, Shuko Harada, William B Hillegass, Lindsay Hines, Richard B Horenstein, Lucius A Howell, Linda J B Jeng, Mark D Kelemen, Yee Ming Lee, Oyunbileg Magvanjav, May Montasser, David R Nelson, Edith A Nutescu, Devon C Nwaba, Ruth E Pakyz, Kathleen Palmer, Josh F Peterson, Toni I Pollin, Alison H Quinn, Shawn W Robinson, Jamie Schub, Todd C Skaar, D Max Smith, Vindhya B Sriramoju, Petr Starostik, Tomasz P Stys, James M Stevenson, Nicholas Varunok, Mark R Vesely, Dyson T Wake, Karen E Weck, Kristin W Weitzel, Russell A Wilke, James Willig, Richard Y Zhao, Rolf P Kreutz, George A Stouffer, Philip E Empey, Nita A Limdi, Alan R Shuldiner, Almut G Winterstein, Julie A Johnson, and IGNITE Network.
• Department of Pharmacotherapy and Translational Research, University of Florida, Gainesville, Florida. Electronic address: lcavallari@cop.ufl.edu.
• JACC Cardiovasc Interv. 2018 Jan 22; 11 (2): 181-191.

ObjectivesThis multicenter pragmatic investigation assessed outcomes following clinical implementation of CYP2C19 genotype-guided antiplatelet therapy after percutaneous coronary intervention (PCI).BackgroundCYP2C19 loss-of-function alleles impair clopidogrel effectiveness after PCI.MethodsAfter 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.ResultsAmong 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).ConclusionsThese 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.Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

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