A multicomponent intervention incorporating CYP2C19 genotype-guided therapy and integrated pharmaceutical care reduces hospitalizations and improves adherence in ischemic stroke
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.
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.
Antithrombotic therapy after percutaneous coronary intervention (PCI) is shifting from fixed 12‐month dual antiplatelet therapy (DAPT) to risk‐stratified, patient‐centered regimens. In this systematic review (80 studies; >330,000 patients), we compare personalized versus fixed DAPT strategies, evaluate abbreviated DAPT in high‐bleeding‐risk (HBR) populations, and evaluate bleeding and ischemic risk scores. Personalized strategies, including genotype‐guided therapy, ultra‐short DAPT (≤1 month) with P2Y12 monotherapy, and 3‐month DAPT, substantially reduce bleeding (often by roughly 25%−65%); ischemic risk after de‐escalation is heterogeneous across populations and strategies, with most trials showing neutrality and one (STOPDAPT‐2 ACS) signaling increased myocardial infarction (MI) when aspirin was withdrawn after 1–2 months of clopidogrel‐based DAPT in acute coronary syndrome (ACS). In HBR patients, 1 to 3‐month DAPT followed by P2Y12 monotherapy lowers major bleeding by up to 65% and may reduce cardiovascular mortality, without increased MI or stent thrombosis in most trials, although ischemic signals varied by population and strategy. In atrial fibrillation, avoiding prolonged triple therapy reduces bleeding by approximately 30%. In ACS, prasugrel is favored over ticagrelor for ischemic outcomes; ARC‐HBR, PRECISE‐DAPT, and the newer PRECISE‐HBR scores show moderate discrimination (c‐statistic 0.64–0.75). Contemporary data therefore support replacing one‐size‐fits‐all 12‐month DAPT with risk‐guided algorithms for post‐PCI antithrombotic therapy.
Thierry Kochkarian, Anis Ismail, Omar Chaabo et al.· Catheterization and cardiova...· 0 citations
Objective To evaluate the lipid-lowering efficacy, anti-inflammatory activity, and short-term prognostic benefit of early evolocumab plus statin in complex high-risk indicated non-revascularized non-ST-elevation acute coronary syndrome (CHIP-NSTEACS) patients. Methods This single-center retrospective cohort study consecutively enrolled 186 CHIP-NSTEACS patients hospitalized from January 2022 to December 2024. Patients were divided into an observation group (high-intensity statin + evolocumab initiated within 48 h of admission, n = 92) and a control group (statin monotherapy, n = 94). Inverse probability of treatment weighting (IPTW) was used to balance baseline covariates. Longitudinal changes in lipid profiles and high-sensitivity C-reactive protein (hs-CRP) were analyzed using repeated-measures ANOVA. The primary endpoint was 3-month major adverse cardiovascular events (MACE). Multivariate Cox regression and Fine-Gray competing risk models were used for survival analysis. Results Baseline characteristics were well-balanced after IPTW (all standardized mean differences <0.1). At 3 months, LDL-C reduction was 61.3% in the observation group vs. 32.2% in the control group (P < 0.001), with target achievement rates (<1.8 mmol/L) of 89.1% vs. 27.7% (P < 0.001). Evolocumab also significantly reduced lipoprotein(a) and hs-CRP (48.7% vs. 26.1% at 1 month, P < 0.001). The 3-month MACE incidence was lower in the observation group (11.96% vs. 28.72%, P = 0.004), driven by reductions in non-fatal myocardial infarction, recurrent angina, and unplanned cardiac rehospitalization. Multivariate Cox regression identified early evolocumab as an independent protective factor against 3-month MACE (HR = 0.42, 95% CI: 0.25–0.71, P = 0.001). No significant between-group difference in adverse events was observed (5.43% vs. 4.26%, P = 0.715). Conclusion Early evolocumab add-on therapy to high-intensity statin achieves potent lipid-lowering and anti-inflammatory effects, improves 3-month clinical outcomes, and has an acceptable safety profile in non-revascularized CHIP-NSTEACS patients. This strategy represents a promising optimized pharmacotherapy for this ultra-high-risk population. Limitations Single-center retrospective design and short follow-up period limit generalizability.
Wen-Bin Jiang, Mei Liu, Xiaoshuan Xiong et al.· Frontiers in Cardiovascular...· 0 citations
Evidence suggests that genotype-guided therapy, PFT-guided treatment, and individualized DAPT duration may improve the balance between ischemic protection and bleeding risk in selected high-risk populations, but routine implementation remains limited by inconsistent clinical outcome benefits.
Sai Praneeth Chaparala, Abhishek Hanumanpratap Singh Kshatri, Amritha Suresh et al.· Journal of Basic and Clinica...· 0 citations
AIMS
Cytochrome P450 2C19 (CYP2C19) genotype testing is recommended to guide antiplatelet selection after ischaemic stroke and transient ischaemic attack. CYP2C19 also metabolizes several commonly prescribed non-antiplatelet drugs. We aimed to quantify exposure to CYP2C19-metabolized drugs in stroke patients at hospital discharge and during longitudinal follow-up.
METHODS
We conducted a retrospective longitudinal cohort study of patients discharged following acute stroke from a tertiary care stroke unit between October 2023 and November 2024. Drugs with established CYP2C19 pharmacogenetic dosing guidance were identified. Exposure was assessed at discharge and over a minimum 1-year follow-up using linked primary care prescribing data. Population-level CYP2C19 metabolizer phenotype frequencies were applied to illustrate potential implications for genotype-informed prescribing.
RESULTS
Among 502 patients prescribed antiplatelet therapy at discharge, 81% were co-prescribed at least one CYP2C19-metabolized non-antiplatelet drug. Proton pump inhibitors predominated (80%), followed by selective serotonin reuptake inhibitors (5.4%) and tricyclic antidepressants (3.6%). In 329 patients with longitudinal data, exposure increased to 83% during follow-up, with antidepressant prescribing approximately doubling. Exposure to two or more CYP2C19-metabolized drugs increased from 8% to 19%. Applying population metabolizer frequencies suggested around one third of CYP2C19-metabolized drug prescriptions at discharge, and during follow-up may have actionable implications.
CONCLUSIONS
Exposure to CYP2C19-metabolized drugs is highly prevalent after acute stroke and increases over time, indicating that CYP2C19 genotype results obtained for antiplatelet selection are likely to have broader longitudinal relevance across commonly prescribed therapies. Guidance should be developed to assist clinicians to incorporate genotype results into prescribing decisions.
Cleodie C Swire, A. Lambarth, Ayesha Saleem et al.· British Journal of Clinical...· 0 citations
This is the first systematic review and meta-analysis to combine an updated quantitative synthesis of functional clopidogrel resistance with a dedicated qualitative appraisal of CYP2C19 genetic determinants, while explicitly separating analyses based on raw event data from exploratory analyses using published effect estimates and applying conservative small-sample sensitivity methods.
M. L. Del Rio-Sola, Sandra Pérez-Fernández, Marina Jiménez-Caja et al.· Clinical Therapeutics· 0 citations
Machine learning (ML) models integrating genetic and clinical data show promise for personalizing antiplatelet therapy after myocardial infarction (MI). This study aimed to develop an ML model using clinical features and CYP2C19 genotype to predict long-term major adverse cardiac events (MACEs) and guide P2Y12 inhibitor selection. In a prospective observational study of 218 MI patients undergoing percutaneous coronary intervention, with up to 9-year follow-up for MACEs, we trained and evaluated multiple models incorporating clinical, genetic, and angiographic variables. Uplift modeling principles were applied to assess treatment heterogeneity, and feature importance was analyzed using Shapley Additive Explanations (SHAP). The optimal model (CatBoost with SHAP-based feature selection) achieved an area under the receiver operating characteristic curve of 0.721. Discrimination remained stable under bootstrap resampling and across both infarction presentations. Key prognostic predictors included age, comorbidity index, number of significant coronary lesions, P2Y12 inhibitor type, stent type, and CYP2C19 loss-of-function/gain-of-function variants. Notably, CYP2C19 variants were significant MACE predictors, while drug-eluting stents and ticagrelor were associated with lower predicted long-term risk. These findings suggest that an ML framework incorporating CYP2C19 genotype can stratify long-term MACE risk. This data-driven approach points to the prognostic utility of genetic testing and supports the potential role of ticagrelor, particularly in genetically defined high-risk MI patients, for optimizing secondary prevention.
Alexander Kirdeev, Konstantin Burkin, A. Vorobev et al.· Journal of Cardiovascular Ph...· 0 citations