Genetic-Guided Oral P2Y12 Inhibitor Selection and Cumulative Ischemic Events After Percutaneous Coronary Intervention

Brenden S. Ingraham, Michael E. Farkouh, Ryan J. Lennon, Derek So, Shaun G. Goodman, Nancy Geller, Jang Ho Bae, Myung Ho Jeong, Linnea M. Baudhuin, Verghese Mathew, Malcolm R. Bell, Amir Lerman, Yi Ping Fu, Ahmed Hasan, Erin Iturriaga, Jean Francois Tanguay, Robert C. Welsh, Yves Rosenberg, Kent Bailey, Charanjit RihalNaveen L. Pereira

Research output: Contribution to journalArticlepeer-review


Background: Genetic-guided P2Y12 inhibitor selection has been proposed to reduce ischemic events by identifying CYP2C19 loss-of-function (LOF) carriers at increased risk with clopidogrel treatment after percutaneous coronary intervention (PCI). A prespecified analysis of TAILOR-PCI (Tailored Antiplatelet Therapy Following PCI) evaluated the effect of genetic-guided P2Y12 inhibitor therapy on cumulative ischemic and bleeding events. Objectives: Here, the authors detail a prespecified analysis of cumulative endpoints. The primary endpoint was cumulative incidence rate of ischemic events at 12 months. Cumulative incidence of major and minor bleeding was a secondary endpoint. Cox proportional hazards models as adapted by Wei, Lin, and Weissfeld were used to estimate the effect of this strategy on all observed events. Methods: The TAILOR-PCI trial was a prospective trial including 5,302 post-PCI patients with acute and stable coronary artery disease (CAD) who were randomized to genetic-guided P2Y12 inhibitor or conventional clopidogrel therapy. In the genetic-guided group, LOF carriers were prescribed ticagrelor, whereas noncarriers received clopidogrel. TAILOR-PCI's primary analysis was time to first event in LOF carriers. Results: Among 5,276 patients (median age 62 years; 25% women; 82% acute CAD; 18% stable CAD), 1,849 were LOF carriers (903 genetic-guided; 946 conventional therapy). The cumulative primary endpoint was significantly reduced in the genetic-guided group compared with the conventional therapy (HR: 0.61; 95% CI: 0.41-0.89; P = 0.011) with no significant difference in cumulative incidence of major or minor bleeding (HR: 1.36; 95% CI: 0.67-2.76; P = 0.39). Conclusions: Among CYP2C19 LOF carriers undergoing PCI, a genetic-guided strategy resulted in a statistically significant reduction in cumulative ischemic events without a significant difference in bleeding.

Original languageEnglish (US)
Pages (from-to)816-825
Number of pages10
JournalJACC: Cardiovascular Interventions
Issue number7
StatePublished - Apr 10 2023


  • P2Y inhibitor
  • antiplatelet therapy
  • genomics
  • individualized medicine
  • percutaneous coronary intervention

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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