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Genotype-guided ticagrelor/prasugrel versus clopidogrel therapy in stroke patients with CYP2C19 loss of function

Mohitosh Biswas1,2,3, Murshadul Alam Murad1, Maliheh Ershadian2,3

  • 1Department of Pharmacy, Faculty of Science, University of Rajshahi, Rajshahi, Bangladesh.

Pharmacogenomics
|December 26, 2025
PubMed

Insights

Patients with transient ischemic attack (TIA) or ischemic stroke (IS) carrying CYP2C19 Loss-of-Function (LoF) alleles benefit from ticagrelor or prasugrel over clopidogrel. This genotype-guided therapy reduces recurrent stroke and vascular events without increasing bleeding risk.

Area of Science:

  • Pharmacogenomics
  • Cardiovascular Medicine
  • Neurology

Background:

  • Patients with transient ischemic attack (TIA) or ischemic stroke (IS) carrying CYP2C19 Loss-of-Function (LoF) alleles face increased risk of recurrent events when treated with clopidogrel.
  • Alternative antiplatelet therapies like prasugrel and ticagrelor are suggested for these patients.

Purpose of the Study:

  • To evaluate the aggregated risk of recurrent stroke or composite vascular events in TIA/IS patients with CYP2C19 LoF alleles treated with genotype-guided prasugrel/ticagrelor versus clopidogrel therapy.

Main Methods:

  • A systematic literature search was conducted to identify relevant studies.
  • RevMan software was utilized to calculate the risk ratio (RR) for primary and secondary outcomes, with statistical significance set at p < 0.05.

Main Results:

  • Six studies encompassing 14,124 TIA/IS patients were analyzed.
  • Ticagrelor/prasugrel therapy in CYP2C19 LoF allele carriers significantly reduced composite vascular events (RR 0.76) and recurrent stroke (RR 0.76) compared to clopidogrel.
  • No significant difference in bleeding events was observed between the treatment groups (RR 0.91).

Conclusions:

  • For TIA/IS patients with CYP2C19 LoF alleles, ticagrelor or prasugrel offers superior clinical benefits over clopidogrel.
  • This genotype-guided approach effectively reduces composite vascular events and recurrent stroke risk without increasing bleeding complications.
Abstract

Keywords:
CYP2C19 loss-of-function allelesStrokeclopidogrelefficacy and safetyprecision medicineticagrelor/prasugrel

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