Safety and Efficacy of 50 mg Enteric Sustained-Release Aspirin Tablet in Secondary Prevention of Mild Ischemic#br#
Stroke/Transient Ischemic Attack#br#

doi:10.3969/j.issn.1673-5765.2021.07.004

Abstract

Abstract: Objective To investigate the efficacy and safety of 50 mg enteric sustained-release aspirin tablet in secondary prevention of mild ischemic stroke/TIA. Methods This was a multicenter, randomized, open, parallel control, non-inferior and prospective

clinical study, which enrolled mild ischemic stroke/TIA patients with onset of 21days to 90 days

from 21 domestic centers. All the patients were randomly divided into observation group (Aspirin enteric-coated sustained release tablet 50 mg once every night) and control group (enteric-coated Aspirin 100 mg once every night). Both groups were treated and followed up for 52 weeks. The recurrence of stroke (ischemic stroke, hemorrhagic stroke and TIA), major adverse cardiovascular events (MACE), all-cause death and adverse events were compared between the two groups. Results A total of 567 patients were enrolled in the study, including 287 patients in observation group and 280 patients in control group. The difference in recurrence rate of stroke and/or TIA (4.53% vs 4.29%, P =0.8454), the incidence of MACE (1.05% vs 1.07%, P =1.0000) and all-cause death (0 vs 0.36%, P =0.4938) between the two groups had no statistical significance. The difference in recurrence rate of stroke and/or TIA between the two groups was -0.0011 (95%CI -0.0300-0.0278) in noninferior test. The difference in incidence of bleeding events between the two group had no statistical significance (observation vs control: 2.09% vs 3.21%, P =0.4045), and one case of gastric ulcer bleeding occurred in the control group. The difference in severe adverse events between the two group also had no statistical significance (observation vs control: 0 vs 0.71%, P =0.2434), including 1 case of fracture and 1 case of death after recurrent stroke both in the control group. Conclusions 50 mg enteric sustained-release aspirin tablets are effective in secondary prevention of mild ischemic stroke/TIA, and the incidence and degree of adverse events are relatively mild. The overall efficacy of secondary prevention of stroke/TIA of 50 mg enteric sustained-release aspirin tablets is not inferior to that of 100 mg aspirin enteric-coated tablets.

Key words: Aspirin; Mild ischemic stroke; Transient ischemic attack; Safety; Efficacy

摘要： 目的研究50 mg阿司匹林肠溶缓释片在轻型缺血性卒中和TIA二级预防中的有效性及安全性。方法通过前瞻性、多中心、随机、开放、平行对照、非劣效性设计的临床研究，在国内21个中心入组发病21～90 d的轻型缺血性卒中和TIA患者，随机分为试验组（每晚口服阿司匹林肠溶缓释片50 mg）和对照组（每晚口服阿司匹林肠溶片100 mg），服药及随访共52周。比较两组的卒中复发率（包括出血性卒中、缺血性卒中和TIA）、主要负性心脏事件（major adverse cardiovascular events，MACE）发生率、全因死亡率和不良事件发生率。结果研究共入组567例患者，试验组287例，对照组280例。试验组与对照组的卒中复发率（4.53% vs 4.29%，P =0.8454），MACE发生率（1.05% vs 1.07%，P =1.0000）及全因死亡率（0 vs 0.36%， P =0.4938）差异均无统计学意义。非劣效检验中，试验组与对照组比较卒中和（或）TIA复发率差值为-0.0011，95%CI为-0.0300～0.0278。试验组与对照组比较出血不良事件发生率差异无统计学意义（2.09% vs 3.21%，P =0.4045），其中1例胃溃疡出血发生在对照组；试验组与对照组比较严重不良事件发生率差异无统计学意义（0. vs 0.71%，P =0.2434)，严重不良事件包括骨折1例，卒中复发后死亡1 例，均发生在对照组。结论每日口服50 mg阿司匹林肠溶缓释片在轻型缺血性卒中和TIA二级预防中有效，不良事件发生率及程度有相对较轻的倾向，预防卒中复发的效果不劣于每日口服100 mg阿司匹林肠溶片。

关键词: 阿司匹林; 轻型缺血性卒中; 短暂性脑缺血发作; 安全性; 有效性

YU Feng-Chun, QI Yan-Yan, ZHANG Jing, GAO Bing, WANG Xue-Hong, ZHAO Feng-Li, WANG Su-Li, FANG Zhi-Yong, QIAO Shu-Dong, BI Qi. Safety and Efficacy of 50 mg Enteric Sustained-Release Aspirin Tablet in Secondary Prevention of Mild Ischemic#br# Stroke/Transient Ischemic Attack#br#[J]. Chinese Journal of Stroke, 2021, 16(07): 657-663.

于逢春, 祁艳艳, 张敬, 高兵, 王雪红, 赵凤丽, 王素丽, 方之勇, 乔淑冬, 毕齐. 50 mg阿司匹林肠溶缓释片在轻型缺血性卒中和短暂性脑缺血发作二级预防中的安全性与有效性研究[J]. 中国卒中杂志, 2021, 16(07): 657-663.

References

[1] 王拥军，李子孝，谷鸿秋，等. 中国卒中报告2019（中
文版）（1）[J]. 中国卒中杂志，2020，15（10）：1037-
1043.
[2] ZHAO D，LIU J，WANG W，et al. Epidemiological
transition of stroke in China：twenty-one-year
observational study from the Sino-MONICA-Beijing
project[J]. Stroke，2008，39（6）：1668-1674.
[3] WANG Y L，WU D，LIAO X，et al. Burden of
stroke in China[J]. Int J Stroke，2007，2（3）：211-
213.
[4] JOHNSTON S C，FAYAD P B，GORELICK P B，et
al. Prevalence and knowledge of transient ischemic
attack among US adults[J]. Neurology，2003，60（9）：
1429-1434.
[5] MEHRAN R，RAO S V，BHATT D L，et al.
Standardized bleeding definitions for cardiovascular
clinical trials：a consensus report from the bleeding
academic research consortium[J]. Circulation，2011，
123（23）：2736-2747.
[6] KLEINDORFER D，PANAGOS P，PANCIOLI A，
et al. Incidence and short-term prognosis of transient
ischemic attack in a population-based study[J].
Stroke，2005，36（4）：720-723.
[7] COULL A J，LOVETT J K，ROTHWELL P M，et
al. Population based study of early risk of stroke
after transient ischaemic attack or minor stroke：
implications for public education and organisation of
services[J]. BMJ，2004，328（7435）：326.
[8] 宋海庆. 小卒中的治疗何去何从？[J/CD]. 中华脑血
管病杂志（电子版），2020，14（1）：37-39.
[9] LOVETT J K，COULL A J，ROTHWELL P M.
Early risk of recurrence by subtype of ischemic
stroke in population-based incidence studies[J].
Neurology，2004，62（4）：569-573.
[10] 中华医学会神经病学分会，中华医学会神经病学分
会脑血管病学组，中国急性缺血性脑卒中诊治指南
2018[J]. 中华神经科杂志，2018，51（9）：666-682.
[11] POWERS W J，RABINSTEIN A A，ACKERSON
T. 2018 guidelines for the early management of
patients with acute ischemic stroke：a guideline for
healthcare professionals from the American Heart
Association/American Stroke Association[J/OL].
Stroke，2018，49（3）：e46-e110[2021-02-11].
https：//doi.org/10.1161/str.0000000000000158.
[12] Boulanger J M，Lindsay M P，Gubitz G，et al.
Canadian stroke best practice recommendations for
acute stroke management：prehospital，emergency
department，and acute inpatient stroke care，6th
edition，update 2018[J]. Int J Stroke，2018，13（9）：
949-984.
[13] ABDELAZIZ H K，SAAD M，POTHINENI N，et
al. Aspirin for primary prevention of cardiovascular
events[J]. J Am Coll Cardiol，2019，73（23）：
2915-2929.
[14] ASCEND Study Collaborative Group. Effects of
aspirin for primary prevention in persons with
diabetes mellitus[J]. N Engl J Med，2018，379（16）：
1529-1539.
[15] GAZIANO J M，BROTONS C，COPPOLECCHIA R，
et al. Use of aspirin to reduce risk of initial vascular
events in patients at moderate risk of cardiovascular
disease（ARRIVE）：a randomised，double-blind，
placebo-controlled trial[J]. Lancet，2018，392
（10152）：1036-1046.
[16] MCNEIL J J，NELSON M R，WOODS R L，et al.
Effect of aspirin on all-cause mortality in the healthy
elderly[J]. N Engl J Med，2018，379（16）：1519-1528.
[17] MCNEIL J J，WOLFE R，WOODS R L，et al. Effect
of aspirin on cardiovascular events and bleeding in
the healthy elderly[J]. N Engl J Med，2018，379（16）：
1509-1518.
[18] HUANG W Y，SAVER J L，WU Y L，et al.
Frequency of intracranial hemorrhage with lowdose
aspirin in individuals without symptomatic
cardiovascular disease a systematic review and
meta-analysis[J]. JAMA Neurol，2019，76（8）：906-
914.
[19] JOHNSON E S，LANES S F，WENTWORTH C E，
et al. A meta regression analysis of the dose response
effect of aspirin on stroke[J/OL]. Arch Intern Med，
1999，159：1248-1253[2021-02-11]. https：//doi.
org/10.1001/archinte.159.11.1248.
[20] PATRONO C. Aspirin as an antiplatelet drug[J]. N
Engl J Med，1994，330（18）：1287-1294.
[21] CATERINA R D，GIANNESSI D，BOEM A，et al.
Equal antiplatelet effects of aspirin 50 or 324 mg/d in
patients after acute myocardial infarction[J]. Thromb
Haemost，1985，54（2）：528-532.
[22] Dutch TIA Trial Study Group，GIJN J V，ALGRA A，
et al. A comparison of two doses of aspirin（30 mg
vs 283 mg a day）in patients after transient ischemic
attack or minor ischemic stroke[J]. N Eng J Med，
1991，325（18）：1261-1266.
[23] Antithrombotic Trialists' Collaboration.
Collaborative meta-analysis of randomized trials
of antiplatelet therapy for prevention of death，
myocardial infarction，and stroke in high risk
patients[J]. BMJ，2002，324（7329）：71-86.
[24] IKEDA Y，SHIMADA K，TERAMOTO T，et
al. Low-dose aspirin for primary prevention of

cardiovascular event in Japanese patients 60 years or

older with atherosclerotic risk factors：a randomized
clinical trial[J]. JAMA，2014，312（23）：2510-2520.
[25] 冯雪茹，刘梅林，刘芳，等. 阿司匹林剂量对高龄老
年患者血小板功能的影响[J]. 北京大学学报（医学
版），2016，48（5）：835-840.
[26] ROTHWELL P M，COOK N R，GAZIANO J M，et
al. Effects of aspirin on risks of vascular events and
cancer according to bodyweight and dose：analysis
of individual patient data from randomised trials[J].
Lancet，2018，392（10145）：387-399.
[27] 中华医学会心血管病学分会女性健康学组，中国医
师协会心血管内科医师分会女医师工作委员会. 女
性抗栓治疗的中国专家建议[J]. 中华心血管病杂志，
2020，48（6）：443-449.

Safety and Efficacy of 50 mg Enteric Sustained-Release Aspirin Tablet in Secondary Prevention of Mild Ischemic#br# Stroke/Transient Ischemic Attack#br#

50 mg阿司匹林肠溶缓释片在轻型缺血性卒中和短暂性脑缺血发作二级预防中的安全性与有效性研究

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