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High Platelet Reactivity Combined with CYP2C19 Genotype in Predicting Outcomes in East Asian Patients Undergoing

Se-Eun Kim1,2, Ho-Sung Jeon1, Tae-Hwa Go3

  • 1Division of Cardiology, Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju Severance Christian Hospital, Wonju, South Korea.

Clinical Pharmacology and Therapeutics
|August 19, 2023
PubMed

Insights

High platelet reactivity (HPR) and CYP2C19 loss-of-function (LoF) genotype increase cardiac risks after drug-eluting stents. Combining these factors improves prediction of stent thrombosis in East Asian patients.

Area of Science:

  • Cardiovascular Medicine
  • Pharmacogenomics
  • Interventional Cardiology

Background:

  • Loss-of-function (LoF) alleles in CYP2C19 are common in East Asians and associated with high platelet reactivity (HPR) and adverse outcomes.
  • Clopidogrel response is influenced by CYP2C19 genotype and platelet function, impacting outcomes after drug-eluting stent (DES) implantation.

Purpose of the Study:

  • To evaluate the added predictive value of combining HPR and CYP2C19 genotype for outcomes in patients treated with DES.
  • To assess the incremental risk stratification provided by combined HPR and CYP2C19 genotype for major adverse cardiac and cerebrovascular events (MACCE) and stent thrombosis.

Main Methods:

  • Analysis of 6,717 Korean patients from the PTRG-DES consortium who underwent DES implantation and had both platelet function test (PFT) and CYP2C19 genotype data.
  • HPR defined as VerifyNow P2Y12 reaction unit ≥ 252. Primary outcome was MACCE at 5 years.
  • Cox proportional hazards models used to assess MACCE risk and interaction effects.

Main Results:

  • Patients with both HPR and CYP2C19 LoF/LoF genotype exhibited the highest MACCE rates (6.2%) and increased risk (aHR: 1.89).
  • Combined HPR and CYP2C19 genotype significantly improved risk prediction for stent thrombosis compared to models using either factor alone.
  • No significant interaction was found between HPR and CYP2C19 genotype for the primary outcome (MACCE).

Conclusions:

  • Combined assessment of PFT and CYP2C19 genotyping may enhance risk prediction for ischemic events in East Asian patients treated with DES and clopidogrel.
  • The combination model offers superior risk stratification for stent thrombosis compared to individual assessments.

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