Paradoxical myocardial infarction risk with dual antiplatelet therapy in East Asian ischaemic stroke: a nationwide real-world cohort study and pharmacogenomic risk prediction model

High prevalence of CYP2C19 loss-of-function alleles (50–60%) in East Asian populations limiting clopidogrel bioactivation, generating population-specific cardiovascular risk under dual antiplatelet therapy

This Taiwanese nationwide cohort study (5,746 patients, 2011–2020) assesses 100-day cardiovascular safety of antithrombotic regimens after ischemic stroke in an East Asian population, where CYP2C19 loss-of-function allele prevalence reaches 50–60%. Dual antiplatelet therapy (aspirin + clopidogrel) is associated with a 17.2-fold increased myocardial infarction risk versus aspirin monotherapy (95% CI 5.61–52.7; NNH 14), a signal robust across all analyses (E-value 33.4). Aspirin monotherapy reduces all-cause mortality by 94% versus no treatment. The EPSAR score incorporating clinical factors achieves a C-statistic of 0.78.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The signal of a 17-fold increased infarction risk under dual therapy is striking and warrants confirmation, but multi-method consistency and the very high E-value strengthen its credibility. The study illustrates the major issue of transposing Western recommendations to populations with high CYP2C19 poor-metabolizer prevalence. The observational design and absence of individual genotyping (inferred prevalence) limit its scope, but the argument for pharmacogenomic stratification is compelling.

Analysis by Dr Thibaut Benquey