Paradoxical myocardial infarction risk with dual antiplatelet therapy in East Asian ischaemic stroke: a nationwide real-world cohort study and pharmacogenomic risk prediction model
Chien-Tung Yang, Jung-Ju Lin, Paul J. Chen, Wei-Lin Hsu, Der-Cherng Chen, Yu-Hsiang Lin, Chao-Hsuan Chen, Cheng-Li Lin, Hsiang-Ming Huang, XianXiu ChenBackground:
Antithrombotic guidelines for secondary stroke prevention are derived predominantly from Western populations, yet East Asian patients exhibit markedly higher cytochrome P450 2C19 (CYP2C19) loss-of-function allele prevalence (50%–60% vs ~25% in Europeans) – polymorphisms essential for clopidogrel bioactivation – potentially generating population-specific cardiovascular risks not captured in Western-derived recommendations.
Objectives:
To characterise the 100-day cardiovascular safety and effectiveness of antithrombotic regimens in East Asian ischaemic stroke patients and to develop a pharmacogenomically informed clinical risk prediction model.
Design:
Nationwide retrospective cohort study.
Methods:
We analysed 5746 adults from Taiwan’s National Health Insurance Research Database (2011–2020) stratified by antithrombotic regimen initiated within 48 h of confirmatory neuroimaging. Primary outcomes – recurrent ischaemic stroke, haemorrhagic stroke, acute myocardial infarction, heart failure and all-cause mortality – were assessed over 100 days. Multivariable Cox regression, propensity score matching, inverse probability weighting, Fine-Gray competing risks models,
Results:
Dual antiplatelet therapy (DAPT; aspirin plus clopidogrel) was associated with a 17.2-fold increased acute myocardial infarction risk versus aspirin monotherapy (95% confidence interval (CI) 5.61–52.7; number needed to harm 14). This signal was robust across all analytical approaches (propensity-matched hazard ratio (HR) 11.8; inverse probability of treatment weighting HR 13.4; competing-risks subdistribution HR 14.8) and yielded an
Conclusion:
DAPT is associated with unexpected myocardial infarction risk in East Asian stroke patients, consistent with CYP2C19-mediated pharmacogenomic vulnerability. These findings challenge the universal applicability of Western-derived guidelines and support integration of pharmacogenomic risk stratification into antithrombotic prescribing for East Asian populations.
Clinical trial registration:
Not applicable (observational study).