Amarenco Pierre, Albers Gregory W, Denison Hans, Easton J Donald, Evans Scott R, Held Peter, Hill Michael D, Jonasson Jenny, Kasner Scott E, Ladenvall Per, Minematsu Kazuo, Molina Carlos A, Wang Yongjun, Wong K S Lawrence, Johnston S Claiborne
From the Department of Neurology and Stroke Center, Bichat University Hospital and Paris-Diderot, Sorbonne University, Paris, France (P.A.); Stanford University Medical Center, Stanford Stroke Center, Palo Alto, CA (G.W.A.); AstraZeneca, Gothenburg, Sweden (H.D., P.H., J.J., P.L.); Department of Neurology, University of California San Francisco (J.D.E.); Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA (S.R.E.); Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, Canada (M.D.H.); Department of Neurology, Perelman School of Medicine, University of Pennsylvania Health System, Philadelphia (S.E.K.); National Cerebral and Cardiovascular Center, Suita, Osaka, Japan (K.M.); Stroke Unit, Hospital Vall d'Hebron, Barcelona, Spain (C.A.M.); Department of Neurology, Tiantan Hospital, Beijing, China (Y.W.); Department of Medicine & Therapeutics, Chinese University of Hong Kong, SAR (K.S.L.W.); and Dell Medical School, University of Texas, Austin (S.C.J.).
Stroke. 2017 Sep;48(9):2480-2487. doi: 10.1161/STROKEAHA.117.017217. Epub 2017 Jul 18.
Ticagrelor is an effective antiplatelet therapy among patients with atherosclerotic disease and, therefore, could be more effective than aspirin in preventing recurrent stroke and cardiovascular events among patients with embolic stroke of unknown source (ESUS), which includes patients with ipsilateral stenosis <50% and aortic arch atherosclerosis.
We randomized 13 199 patients with a noncardioembolic, nonsevere ischemic stroke or high-risk transient ischemic attack to ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2-90) or aspirin (300 mg on day 1 followed by 100 mg daily for days 2-90) within 24 hours of symptom onset. In all patients, investigators informed on the presence of ipsilateral stenosis ≥50%, small deep infarct <15 mm, and on cardiac source of embolism detected after enrollment or rare causes, which allowed to construct an ESUS category in all other patients with documented brain infarction. The primary end point was the time to the occurrence of stroke, myocardial infarction, or death within 90 days.
ESUS was identified in 4329 (32.8%) patients. There was no treatment-by-ESUS category interaction (=0.83). Hazard ratio in ESUS patients was 0.87 (95% confidence interval, 0.68-1.10; =0.24). However, hazard ratio was 0.51 (95% confidence interval, 0.29-0.90; =0.02) in ESUS patients with ipsilateral stenosis <50% or aortic arch atherosclerosis (n=961) and 0.98 (95% confidence interval, 0.76-1.27; =0.89) in the remaining ESUS patients (n=3368; for heterogeneity =0.04).
In this post hoc, exploratory analysis, we found no treatment-by-ESUS category interaction. ESUS subgroups have heterogeneous response to treatment (Funded by AstraZeneca).
URL: http://www.clinicaltrials.gov. Unique identifier: NCT01994720.
替格瑞洛是动脉粥样硬化疾病患者中一种有效的抗血小板治疗药物，因此，在预防不明来源栓塞性卒中（ESUS）患者的复发性卒中和心血管事件方面，可能比阿司匹林更有效，ESUS患者包括同侧狭窄<50%和主动脉弓动脉粥样硬化的患者。
我们将13199例非心源性、非严重缺血性卒中或高危短暂性脑缺血发作患者在症状发作后24小时内随机分为替格瑞洛组（第1天负荷剂量180mg，随后第2 - 90天每日2次，每次90mg）或阿司匹林组（第1天300mg，随后第2 - 90天每日100mg）。在所有患者中，研究人员了解同侧狭窄≥50%、小的深部梗死<15mm的情况，以及入组后检测到的心脏栓塞源或罕见病因，这使得在所有其他有记录的脑梗死患者中构建ESUS类别成为可能。主要终点是90天内发生卒中、心肌梗死或死亡的时间。
4329例（32.8%）患者被确定为ESUS。不存在治疗与ESUS类别之间的交互作用（P = 0.83）。ESUS患者的风险比为0.87（95%置信区间，0.68 - 1.10；P = 0.24）。然而，同侧狭窄<50%或主动脉弓动脉粥样硬化的ESUS患者（n = 961）的风险比为0.51（95%置信区间，0.29 - 0.90；P = 0.02），其余ESUS患者（n = 3368；异质性P = 0.04）的风险比为0.98（95%置信区间，0.76 - 1.27；P = 0.89）。
在这项事后探索性分析中，我们未发现治疗与ESUS类别之间的交互作用。ESUS亚组对治疗的反应具有异质性（由阿斯利康资助）。
