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

JACC Cardiovasc Interv. 2023 Apr 10;16(7):816-825. doi: 10.1016/j.jcin.2023.01.356.

Abstract

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. (Tailored Antiplatelet Therapy Following PCI [TAILOR-PCI]; NCT01742117).

Keywords: P2Y(12) inhibitor; antiplatelet therapy; genomics; individualized medicine; percutaneous coronary intervention.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Acute Coronary Syndrome* / therapy
  • Clopidogrel / adverse effects
  • Coronary Artery Disease* / complications
  • Coronary Artery Disease* / diagnostic imaging
  • Coronary Artery Disease* / therapy
  • Cytochrome P-450 CYP2C19 / genetics
  • Female
  • Hemorrhage / etiology
  • Humans
  • Male
  • Middle Aged
  • Percutaneous Coronary Intervention* / adverse effects
  • Platelet Aggregation Inhibitors / adverse effects
  • Prospective Studies
  • Purinergic P2Y Receptor Antagonists / adverse effects
  • Treatment Outcome

Substances

  • Clopidogrel
  • Platelet Aggregation Inhibitors
  • Cytochrome P-450 CYP2C19
  • Purinergic P2Y Receptor Antagonists

Associated data

  • ClinicalTrials.gov/NCT01742117