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

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).

• Authors: 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 Rihal, Naveen L Pereira
• Journal: JACC. Cardiovascular interventions (JACC Cardiovasc Interv) Vol. 16 Issue 7 Pg. 816-825 (04 10 2023) ISSN: 1876-7605 [Electronic] United States
• PMID: 37045502 (Publication Type: Randomized Controlled Trial, Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2023. Published by Elsevier Inc.

Chemical References

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

Topics

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