A multicomponent intervention incorporating CYP2C19 genotype-guided therapy and integrated pharmaceutical care reduces hospitalizations and improves adherence in ischemic stroke

Abstract

Background In ischemic stroke patients, antiplatelet therapy faces challenges from CYP2C19 genetic variability and poor post-discharge medication adherence, yet the value of integrating genotyping with comprehensive pharmaceutical care remains unclear across different recurrence risk populations. Methods This single-center, prospective, parallel-group, open-label, assessor-blinded randomized controlled trial enrolled 300 ischemic stroke patients to evaluate a complex pharmacist-led intervention incorporating CYP2C19 genotype-guided antiplatelet therapy (individualized group, n = 150) versus routine care (control group, n = 150). Results In the individualized treatment group, the proportion of patients with intermediate or poor CYP2C19 metabolizer phenotypes who received antiplatelet therapy adjustments was significantly higher (48.72 and 77.27% vs. 10.00%, p < 0.001), and genotype was positively correlated with medication adjustment (ρ = 0.476, p < 0.001). After 1 year, negative binomial regression showed that the individualized group had significantly lower hospitalization frequency than the control group (IRR = 0.700, 95% CI: 0.491–0.999, p = 0.049), and ANCOVA revealed significantly higher medication adherence (adjusted mean difference = 0.533, 95% CI: 0.250–0.815, p < 0.001). Subgroup analysis stratified by ESRS score showed that the beneficial effect of individualized treatment on reducing hospitalization was more pronounced in high-risk patients (ESRS ≥ 3: IRR = 0.640, 95% CI: 0.425–0.965, p = 0.033), whereas the effect in the low-risk group (ESRS < 3) did not reach statistical significance. After multivariable adjustment, the between-group difference in adverse reactions was not statistically significant (OR = 0.543, 95% CI: 0.279–1.057, p = 0.072). Conclusion A multicomponent intervention comprising CYP2C19 genotype-guided therapy and intensive pharmacist-led integrated pharmaceutical care significantly improved medication adherence and reduced hospitalization frequency, with more pronounced benefits observed in patients at high risk of stroke recurrence, without increasing the risk of adverse drug reactions. However, the specific contribution of genotyping alone cannot be isolated from the overall care package.