Safety and Efficacy of CYP2C19 Genotype-Guided Escalation of P2Y12 Inhibitor Therapy After Percutaneous Coronary Intervention in Chronic Kidney Disease: a Post Hoc Analysis of the TAILOR-PCI Study

Roy O. Mathew, Mandeep S. Sidhu, Charanjit S. Rihal, Ryan Lennon, Mohammed El-Hajjar, Neil Yager, Radmila Lyubarova, Khaled Abdul-Nour, Steven Weitz, D. Fearghas O’Cochlain, Vishakantha Murthy, Justin Levisay, Kevin Marzo, John Graham, Vlad Dzavik, Derek So, Shaun Goodman, Yves D. Rosenberg, Naveen Pereira, Michael E. Farkouh

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: Chronic kidney disease (CKD) is a risk factor for ischemic and bleeding events with dual antiplatelet therapy after percutaneous coronary intervention (PCI). Whether the presence of CYP2C19 loss of function (LOF) alleles modifies this risk, and whether a genotype-guided (GG) escalation of P2Y12 inhibitor therapy post PCI is safe in this population is unclear. Methods: This was a post hoc analysis of randomized patients in TAILOR PCI. Patients were divided into two groups based on estimated glomerular filtration rate (eGFR) threshold of < 60 ml/min/1.73 m2 for CKD (n = 539) and non-CKD (n = 4276). The aggregate of cardiovascular death, stroke, myocardial infarction, stent thrombosis, and severe recurrent coronary ischemia at 12-months post-PCI was assessed as the primary endpoint. Secondary endpoint was major or minor bleeding. Results: Mean (standard deviation) eGFR among patients with CKD was 49.5 (8.4) ml/min/1.72 m2. Among all patients, there was no significant interaction between randomized strategy and CKD status for any endpoint. Among LOF carriers, the interaction between randomized strategy and CKD status on composite ischemic outcome was not significant (p = 0.2). GG strategy was not associated with an increased risk of bleeding in either CKD group. Conclusions: In this exploratory analysis, escalation of P2Y12 inhibitor therapy following a GG strategy did not reduce the primary outcome in CKD. However, P2Y12 inhibitor escalation following a GG strategy was not associated with increased bleeding risk in CKD. Larger studies in CKD are needed. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT01742117?term=TAILOR-PCI&draw=2&rank=1. NCT01742117.

Original languageEnglish (US)
Pages (from-to)447-457
Number of pages11
JournalCardiovascular Drugs and Therapy
Volume38
Issue number3
DOIs
StatePublished - Jun 2024

Keywords

  • Antiplatelet therapy
  • CYP2C19
  • Chronic kidney disease
  • Coronary artery disease
  • Percutaneous coronary intervention
  • Pharmacogenomics

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine
  • Pharmacology (medical)

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