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January 10, 2026Stroke2 citations

Why Genetics Can’t Be Ignored in Secondary Stroke Prevention: The CYP2C19 Challenge in Asia

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ARAnushika RahejaDSDeidre Anne De SilvaKNKaavya Narasimhalu

Key Result

Genotype-guided alternatives to clopidogrel, like ticagrelor and cilostazol, significantly lower recurrent stroke risk in CYP2C19 loss-of-function carriers in Asia.

Key Points

  • Evaluate the impact of CYP2C19 loss-of-function alleles on secondary stroke prevention strategies, particularly in Asia.
  • Reviewed trials including CHANCE-2 for efficacy of clopidogrel alternatives
  • Analyzed prevalence of CYP2C19 alleles in South and East Asians
  • Assessed barriers to genetic testing and genotype-guided therapy
  • 75% of South and East Asians carry CYP2C19 loss-of-function alleles
  • Genotype-guided alternatives like ticagrelor and cilostazol reduce recurrent stroke risk
  • Clinical adoption of genotype testing is limited due to infrastructure and cost challenges

Structured PICO

Does genotype-guided antiplatelet therapy reduce recurrent stroke risk in Asian patients requiring secondary stroke prevention compared to standard clopidogrel?

P
Population
South and East Asian patients requiring secondary stroke prevention, specifically CYP2C19 loss-of-function carriers
I
Intervention
Genotype-guided antiplatelet therapy (e.g., ticagrelor, cilostazol)
C
Comparator
Standard clopidogrel therapy
O
Outcome
Recurrent stroke risk

Genotype-guided antiplatelet therapy is essential for secondary stroke prevention in Asia due to the high prevalence of CYP2C19 loss-of-function alleles that reduce clopidogrel efficacy.

Abstract

Stroke is a leading cause of death and disability globally, with Asia disproportionately affected. A critical barrier to effective secondary prevention is the high prevalence of CYP2C19 loss-of-function alleles, present in almost 75% of South and East Asians, which reduce clopidogrel efficacy. Evidence from trials, including CHANCE-2 (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events), shows that genotype-guided alternatives, including ticagrelor and cilostazol, substantially lower recurrent stroke risk in loss-of-function carriers. Yet, clinical adoption remains limited by insufficient genetic testing infrastructure, cost, guideline gaps, and clinician training. Despite these challenges, genotype-guided therapy is both feasible and cost-effective, with the potential to reduce recurrent strokes, disability, and healthcare burden. Urgent action is required to implement precision antiplatelet strategies, update guidelines, and ensure equitable access, making pharmacogenomics a central component of stroke care in Asia.

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Cite This Study

Raheja et al. (2025) studied this question. Genotype-guided alternatives to clopidogrel, like ticagrelor and cilostazol, significantly lower recurrent stroke risk in CYP2C19 loss-of-function carriers in Asia.

synapsesocial.com/papers/6963223291e05aa366cb8c9ahttps://doi.org/10.1161/strokeaha.125.053534
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