Key result
Clopidogrel plus aspirin did not significantly reduce 1-year stroke recurrence compared to aspirin alone in CYP2C19 loss-of-function allele carriers overall (HR 0.83; 95% CI 0.64-1.09).
Why the study?
Dual antiplatelet therapy (DAT) with clopidogrel plus aspirin is suggested for minor stroke (MS) and transient ischemic attack (TIA), but potential subgroups that benefit remain to be identified based on CYP2C19 genotype and risk profile.
Does dual antiplatelet therapy with clopidogrel plus aspirin reduce stroke recurrence compared to aspirin alone in Chinese patients with minor stroke or TIA, depending on CYP2C19 genotype and risk profile?
Cohort (n=2,933)
Does dual antiplatelet therapy with clopidogrel plus aspirin reduce stroke recurrence compared to aspirin alone in Chinese patients with minor stroke or TIA, depending on CYP2C19 genotype and risk profile?
Hazard Ratio: 0.83 (95% CI 0.64–1.09)
Absolute Event Rate: 11.2% vs 13.3%
The efficacy of clopidogrel plus aspirin for secondary stroke prevention in minor stroke or TIA is dependent on both CYP2C19 genotype and clinical risk profile, with high-risk LoFA carriers still benefiting from dual therapy.
Does not support adding clopidogrel to aspirin in CYP2C19 LOF carriers post-stroke; confirms limited efficacy of clopidogrel in this genetic subgroup.
OBJECTIVE: Dual antiplatelet therapy (DAT) with clopidogrel plus aspirin has been suggested by American Heart Association/American Stroke Association guidelines for minor stroke (MS) and transient ischemic attack (TIA) patients. The purpose of this study was to find the potential subgroups that benefit from DAT. We aimed to compare the efficacy of clopidogrel-aspirin therapy with that of aspirin therapy in MS/TIA patients stratified by CYP2C19 genotype and risk profiles. METHODS: CYP2C19 loss-of-function allele (LoFA) carriers were defined as patients with LoFA of either *2 or *3. Low- and high-risk profile was defined as Essen Stroke Risk Score (ESRS) <3 and ≥3, respectively. Stroke recurrence at 1 year was considered primary outcome. RESULTS: Of a total 2,933 MS/TIA patients, there were 1,726 (58.8%) LoFA carriers and 1,068 (36.4%) patients at high risk (ESRS ≥3). No significant difference for stroke recurrence between the clopidogrel-aspirin group and aspirin alone group was found in LoFA carriers (11.2% vs 13.3%, hazard ratio [HR] = 0.83, 95% confidence interval [CI] = 0.64~1.09). In stratified analyses by CYP2C19 genotype and ESRS, HRs (95% CIs) of the clopidogrel-aspirin therapy for stroke recurrence were 1.00 (0.70~1.42), 0.63 (0.41~0.97), 0.62 (0.40~0.96), and 0.52 (0.31~0.88) among subgroups of LoFA carriers at low risk, LoFA carriers at high risk, LoFA noncarriers at low risk, and LoFA noncarriers at high risk, respectively, with p = 0.021 for interaction. INTERPRETATION: Overall, LoFA carriers do not benefit from DAT, but there is significant benefit for LoFA carriers who are at high risk. The benefit of clopidogrel in Chinese MS/TIA patients depends on CYP2C19 genotype and risk profile. ANN NEUROL 2019;86:419-426.
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Xu et al. (2019) conducted a cohort in Minor stroke (MS) and transient ischemic attack (TIA) (n=2,933). Clopidogrel plus aspirin vs. Aspirin alone was evaluated on Stroke recurrence at 1 year (HR 0.83, 95% CI 0.64-1.09). Clopidogrel plus aspirin did not significantly reduce 1-year stroke recurrence compared to aspirin alone in CYP2C19 loss-of-function allele carriers overall (HR 0.83; 95% CI 0.64-1.09).
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