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Impact of CYP2C19*2 on Clopidogrel Response and Cardiovascular Outcomes in ST-segment elevation myocardial infarction

Abdur Razaq1, Waheed Lqbal2, Syed Tahir Shah3

  • 1Abdur Razaq, Institute of Pharmaceutical Sciences, Khyber Medical University Peshawar, Pakistan.

Pakistan Journal of Medical Sciences
|February 25, 2026
PubMed

Insights

Genetic variations in CYP2C19*2 influence clopidogrel effectiveness. Patients with non-functional CYP2C19*2 alleles (GA/AA genotypes) faced higher cardiovascular events after PCI for STEMI, unlike normal metabolizers (GG genotype).

Area of Science:

  • Pharmacogenomics
  • Cardiovascular Medicine
  • Clinical Genetics

Background:

  • Clopidogrel is crucial for preventing cardiovascular events (CVEs) in ST-segment elevation myocardial infarction (STEMI) patients undergoing percutaneous coronary intervention (PCI).
  • Despite adherence, a significant number of patients experience CVEs post-PCI.
  • The metabolic activation of clopidogrel is influenced by genetic polymorphisms, notably CYP2C19*2.

Purpose of the Study:

  • To investigate the association between CYP2C19*2 (rs4244285) genetic polymorphisms and the occurrence of CVEs in STEMI patients post-PCI.
  • To determine if variations in CYP2C19*2 affect clopidogrel's efficacy in preventing post-PCI cardiovascular complications.

Main Methods:

  • A prospective cohort study involving 204 STEMI patients (age 30-75) undergoing PCI.
  • Genotyping for CYP2C19*2 (rs4244285) was performed using TaqMan assay.
  • Patients were followed for 12 months to record CVEs (mortality, stent thrombosis, recurrent MI, ischemic events, stroke); statistical analysis included Fisher's exact test and logistic regression.

Main Results:

  • The CYP2C19*2 (rs4244285) GA and AA genotypes were significantly associated with increased CVEs (p < 0.003).
  • Patients with GG genotype (normal metabolizers) showed a significantly lower incidence of CVEs.
  • Specific CVEs observed included mortality (n=10), stent thrombosis (n=5), recurrent MI (n=9), ischemia-related hospitalizations (n=17), and cerebrovascular accidents (n=3), with higher rates in GA/AA groups.

Conclusions:

  • Carriage of one or two non-functional CYP2C19*2 alleles (GA/AA genotypes), classifying individuals as intermediate or poor metabolizers, is significantly associated with higher rates of CVEs post-PCI.
  • Normal metabolizers (GG genotype) exhibited a significantly lower incidence of CVEs, highlighting the impact of genetic variations on clopidogrel's clinical outcomes.
Abstract

Keywords:
CYP2C19 *2 gene polymorphismsCardiovascular Events (CVEs) Percutaneous coronary intervention (PCI)ClopidogrelST-segment elevation myocardial infarction (STEMI)

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