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. Lowand 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 M inor stroke (MS) and transient ischemic attack (TIA) are warning signs of an impending stroke. The estimated risk of recurrent stroke occurring after an MS or TIA is estimated from 3.7% to 11.7% within 3 months. 1-4 Recent large clinical trial studies have shown that dual antiplatelet therapy (DAT) with clopidogrel and aspirin reduces the rate of recurrent stroke during the first 3 months after an MS or TIA. 3,4 The clopidogrel-aspirin antiplatelet therapy has been recommended for acute MS and TIA patients by the American Heart Association/American Stroke Association guidelines. 5,6 Clopidogrel blocks platelet aggregation as an adenosine diphosphate receptor antagonist, a mechanism that is synergistic with aspirin in platelet-aggregation assays. 7View this article online at wileyonlinelibrary.com.
High blood pressure (BP) is frequent in acute ischemic stroke (IS). However, the impact of BP change patterns during acute phase on clinical outcomes is not conclusive. This study aims to investigate the association between the acute‐phase BP trajectories and clinical outcomes in IS patients with high admission BP. The cohort consisted of 316 IS patients with admission systolic BP (SBP) ≥160 mm Hg. SBP trajectories during the first 7 days after onset were characterized using a random effects model. The patients were classified into three groups based on the SBP trajectory curve parameters: sustained high SBP (T1), moderate decrease (T2), and rapid decrease in SBP (T3). Poor outcomes were defined as modified Rankin scale score ≥3 in 3 months after onset. The relationship between SBP trajectory groups and the outcome was examined in multivariable logistic regression models. The decreasing trend was greater in the favorable than in the poor outcome group (P = 0.028 for difference in linear slopes). The incidence of poor outcomes was 25.9%, 13.5%, and 9.8% in T1 (n = 54), T2 (n = 170), and T3 (n = 92) groups, respectively. Compared with T1 group, the decrease in SBP in T2 and T3 groups was significantly associated with lower risk of the poor outcome (odds ratio = 0.25, 95% confidence interval = 0.10‐0.67, P = 0.006). These findings suggest that a decrease in BP in the acute phase is predictive of favorable outcomes in IS patients. BP trajectories have a greater power to detect the association than individual BP values at one time‐point.
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