Multisite Investigation of Outcomes With Implementation of CYP2C19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention.
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.
Cavallari, LH; Lee, CR; Beitelshees, AL; Cooper-DeHoff, RM; Duarte, JD; Voora, D; Kimmel, SE; McDonough, CW; Gong, Y; Dave, CV; Pratt, VM; Alestock, TD; Anderson, RD; Alsip, J; Ardati, AK; Brott, BC; Brown, L; Chumnumwat, S; Clare-Salzler, MJ; Coons, JC; Denny, JC; Dillon, C; Elsey, AR; Hamadeh, IS; Harada, S; Hillegass, WB; Hines, L; Horenstein, RB; Howell, LA; Jeng, LJB; Kelemen, MD; Lee, YM; Magvanjav, O; Montasser, M; Nelson, DR; Nutescu, EA; Nwaba, DC; Pakyz, RE; Palmer, K; Peterson, JF; Pollin, TI; Quinn, AH; Robinson, SW; Schub, J; Skaar, TC; Smith, DM; Sriramoju, VB; Starostik, P; Stys, TP; Stevenson, JM; Varunok, N; Vesely, MR; Wake, DT; Weck, KE; Weitzel, KW; Wilke, RA; Willig, J; Zhao, RY; Kreutz, RP; Stouffer, GA; Empey, PE; Limdi, NA; Shuldiner, AR; Winterstein, AG; Johnson, JA; IGNITE Network,
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