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急性基底动脉闭塞患者早期血管内治疗联用丁苯酞的多中心、前瞻性队列研究
Safety and efficacy of early endovascular therapy combined with butylphthalide for acute basilar artery occlusion: a multicenter, prospective cohort study
- 第三军医大学学报 2021年43卷第2期 页码：124-130
- 作者机构：
1.400037 重庆, 陆军军医大学(第三军医大学)第二附属医院神经内科
2.310006 杭州，杭州市第一人民医院神经内科
3.130000 长春，吉林大学白求恩第一医院神经内科
4.541002 广西 桂林，中国人民解放军联勤保障部队第九二四医院神经内科
5.276000 山东 临沂，临沂市人民医院神经内科
6.350025 福州，中国人民解放军联勤保障部队第九○○医院神经内科
7.473009 河南 南阳，南阳市中心医院神经内科
8.430022 武汉，武汉市第一医院神经内科
9.410004 长沙，长沙市中心医院神经内科
- 作者简介：
[ 龚自力, E-mail:gzl_944@163.com GONG Zili, E-mail: gzL_944@163.com
- 基金信息：国家杰出青年科学基金(81525008);陆军军医大学临床医学科研人才培养计划(2018XLC2013);河南省重点研发与推广项目(192102310349)
DOI：10.16016/j.1000-5404.202008058
中图分类号： R743.3;R969.4;R972收稿：2020-08-07，
修回：2020-08-26，
纸质出版：2021-01-30
- 稿件说明：
移动端阅览
刘帅, 资文杰, 邱忠明, 等. 急性基底动脉闭塞患者早期血管内治疗联用丁苯酞的多中心、前瞻性队列研究[J]. 第三军医大学学报, 2021,43(2):124-130.
Shuai LIU, Wenjie ZI, Zhongming QIU, et al. Safety and efficacy of early endovascular therapy combined with butylphthalide for acute basilar artery occlusion: a multicenter, prospective cohort study[J]. Journal of Third Military Medical University, 2021, 43(2): 124-130.
刘帅, 资文杰, 邱忠明, 等. 急性基底动脉闭塞患者早期血管内治疗联用丁苯酞的多中心、前瞻性队列研究[J]. 第三军医大学学报, 2021,43(2):124-130. DOI： 10.16016/j.1000-5404.202008058.
Shuai LIU, Wenjie ZI, Zhongming QIU, et al. Safety and efficacy of early endovascular therapy combined with butylphthalide for acute basilar artery occlusion: a multicenter, prospective cohort study[J]. Journal of Third Military Medical University, 2021, 43(2): 124-130. DOI： 10.16016/j.1000-5404.202008058.
摘要
目的
2
探讨急性基底动脉闭塞患者早期血管内治疗联用丁苯酞的有效性及安全性。
方法
2
连续性纳入2014年1月至2019年5月在陆军军医大学第二附属医院及46家分中心的急性基底动脉闭塞早期接受血管内治疗患者，依据是否使用丁苯酞药物治疗，将其分为丁苯酞组和对照组，比较90 d良好功能预后发生率、48 h内症状性颅内出血(symptomatic intracranial hemorrhage
sICH)和90 d病死率。采用二元Logistic回归探讨丁苯酞与90 d功能预后、sICH发生率及90 d病死率的相关性，校正因素包括年龄、血压、发病到穿刺时间、mTICI血流分级、糖尿病、基线NIHSS评分、后循环Alberta卒中项目早期CT评分、闭塞部位等混杂因素。
结果
2
最终共纳入患者645例，丁苯酞组232例，对照组413例。丁苯酞组90 d良好功能预后比例显著高于对照组[39.2%(91/232)
vs
28.1%(116/413)；χ
2
=8.454，
P
=0.005
]
；丁苯酞组患者sICH发生率明显低于对照组[1.7%(4/232)
vs
10.2%(41/403)，χ
2
=15.965，
P
<
0.001
]
；丁苯酞组90 d病死率显著低于对照组[34.1%(79/232)
vs
52.8%(218/413)，χ
2
=20.983，
P
<
0.001
]
。使用丁苯酞治疗是90 d良好功能预后(
OR
: 1.646，95%
CI
1.091~2.483，
P
=0.018)、降低sICH发生率(
OR
: 0.164，95%
CI
：0.056~0.475，
P
=0.001)及90 d病死率(
OR
: 0.424，95%
CI
: 0.278~0.647，
P
<
0.001)的独立保护因素。
结论
2
早期血管内治疗联用丁苯酞可显著改善急性基底动脉闭塞患者的90 d功能预后，降低sICH风险及病死率。
Abstract
Objective
2
To investigate the efficacy and safety of early endovascular therapy (EVT) combined with butylphthalide (NBP) in the patients with acute basilar artery occlusion (BAO).
Methods
2
From January 2014 to May 2019
645 acute BAO patients (from the Second Affiliated Hospital of Army Medical University and other 46 comprehensive stroke centers in China) who underwent EVT were enrolled into this study. According to receiving NBP treatment or not
the patients were divided into simple EVT group (control group
n
=413) and EVT+NBP group (NBP group
n
=232). Safety and efficacy were evaluated and compared between the 2 groups
with symptomatic intracerebral hemorrhage (sICH) within 48 h and 90-day all cause mortality as evaluation criteria for safety
and the modified Rankin Scale (mRS) score and the modified Thrombolysis in Cerebral Infarction (mTICI) for efficacy. Binary Logistic regression was used for multi-factor analysis
with calibration factors of age
blood pressure
time from onset to puncture
mTICI grade
diabetes mellitus
baseline NIHSS score
pc-ASPECTS score
ASITN/SIR grade and occlusion sites
etc.
Results
2
At 90 d after treatment
the NBP group had a higher rate of mRS low score (≤3) than the control g
roup [39.2% (91/232)
vs
28.1% (116/413)
Chi
-square=8.454
P
=0.005
]
indicating better functional prognosis. The incidence of sICH [1.7% (4/232)
vs
10.2% (41/403)
Chi
-square=15.965
P
<
0.001
]
and 90-day mortality [34.1% (79/232)
vs
52.8% (218/413)
Chi
-square=20.983
P
<
0.001
]
were both significantly lower in the NBP group when compared to the control group. Logistic regression analysis indicated that NBP was an independent protective factor for good functional prognosis at 90 d (
OR
=1.646
95%
CI
: 1.091~2.483
P
=0.018)
reduced incidence of sICH (
OR
=0.164
95%
CI
: 0.056~0.475
P
=0.001) and lower mortality at 90 d (
OR
=0.424
95%
CI
: 0.278~0.647
P
<
0.001).
Conclusion
2
Early EVT combined with NBP can significantly improve the 90-day functional prognosis
and reduce the sICH risk and mortality in the acute BAO patients.
关键词
Keywords
references
HETTS S W. Diving into a shallow pool: endovascular treatment for basilar artery occlusion[J]. Radiology, 2019, 291(3): 738-739. DOI: 10.1148/radiol.2019190375.
刘新峰, 刘鸣, 崔丽英.中国急性缺血性脑卒中早期血管内介入诊疗指南2018[J].中华神经科杂志, 2018, 51(9): 683-691.DOI: 10.3760/cma.j.issn.1006-7876.2018.09.005.
LIU X F, LIU M, CUI L Y.Chinese guidelines for the endovascular treatment of acute ischemic stroke 2018[J]. Chin J Neurol, 2018, 51(9): 683-691. DOI: 10.3760/cma.j.issn.1006-7876.2018.09.005.
POWERS W J, RABINSTEIN A A, ACKERSON T, et al . Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A guideline for healthcare professionals from the American Heart Associat ion/American Stroke Association[J ] . Stroke, 2019, 50(12): e344-e418. DOI: 10.1161/STR.0000000000000211.
VILLRINGER K, ZIMNY S, GALINOVIC I, et al . The association between recanalization, collateral flow, and reperfusion in acute stroke patients: a dynamic susceptibility contrast MRI study[J ] . Front Neurol,2019, 10: 1147. DOI: 10.3389/fneur.2019.01147.
CHENG X, WANG H, LIU C, et al . Dl-3-n-butylphthalide promotes remyelination process in cerebral white matter in rats subjected to ischemic stroke[J ] . Brain Res, 2019, 1717: 167-175. DOI: 10.1016/j.brainres.2019.03.017.
LI F, MA Q, ZHAO H, et al . L-3-n-Butylphthalide reduces ischem ic stroke injury and increases M2 microglial polarization[J ] . Metab Brain Dis, 2018, 33(6): 1995-2003. DOI: 10.1007/s11011-018-0307-2.
SUN Y, CHENG X, WANG H, et al . Dl-3-n-butylphthalide promotes neuroplasticity and motor recovery in stroke rats[J ] . Behav Brain Res, 2017, 329: 67-74. DOI: 10.1016/j.bbr.2017.04.039.
YIN W, LAN L, HUANG Z, et al . Discovery of a ring-opened derivative of 3-n-butylphthalide bearing NO/H 2 S-donating moieties as a potential anti-ischemic stroke agent[J ] . Eur J Med Chem, 2016, 115: 369-380. DOI: 10.1016/j.ejmech.2016.03.044..
WANG S, MA F, HUANG L, et al . Dl-3-n-butylphthalide (NBP): a promising therapeutic agent for ischemic stroke[J ] . CNS Neurol Disord Drug Targets, 2018, 17(5): 338-347. DOI: 10.2174/1871527317666180612125843.
ZHANG C, ZHAO S, ZANG Y, et al . The efficacy and safety of dl-3n-butylphthalide on progressive cerebral infarction: a randomized controlled STROBE study[J ] . Medicine (Baltimore), 2017, 96(30): e7257. DOI: 10.1097/md.0000000000007257.
ZHAO H, YUN W, ZHANG Q, et al . Mobilization of circulating endothelial progenitor cells by dl-3-n-butylphthalide in acute ischemic stroke patients[J ] . J Stroke Cerebrovasc Dis, 2016, 25(4): 752-760. DOI: 10.1016/j.jstrokecerebrovasdis.2015.11.018.
黄菲虹, 肖露露, 李顺, 等.丁苯酞氯化钠注射液联合介入治疗急性前循环大血管闭塞性卒中患者的疗效观察[J].中华神经科杂志, 2019, 52(7): 555-561. DOI: 10.3760/cma.j.issn.1006-7876.2019.07.007.
HUANG F H, XIAO L L, LI S, et al . The effect of butylphthalide injection combined with interventional therapy on patients with acute anterior circulation large vessel occlusive stroke[J ] . Chin J Neurol, 2019, 52(7): 555-561. DOI: 10.3760/cma.j.issn.1006-7876.2019.07.007.
ADAMS H P, BENDIXEN B H, KAPPELLE L J, et al . Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment[J ] . Stroke, 1993, 24(1): 35-41. DOI: 10.1161/01.str.24.1.35.
PALLESEN L P, GERBER J, DZIALOWSKI I, et al . Diagnostic and prognostic impact of pc-ASPECTS applied to perfusion CT in the basilar artery international cooperation study[J ] . J Neuroimaging, 2015, 25(3): 384-389. DOI: 10.1111/jon.12130.
SINGER O C, BERKEFELD J, NOLTE C H, et al . Collateral vessels in proximal mid dle cerebral artery occlusion: the ENDOSTROKE study[J ] . Radiology, 2015, 274(3): 851-858. DOI: 10.1148/radiol.14140951.
DARGAZANLI C, FAHED R, BLANC R, et al . Modified thrombolysis in cerebral infarction 2C/thrombolysis in cerebral infarction 3 reperfusion should be the aim of mechanical thrombectomy: insights from the ASTER trial (contact aspiration versus stent retriever for successful revascularization)[J ] . Stroke, 2018, 49(5): 1189-1196. DOI: 10.1161/strokeaha.118.020700.
VON KUMMER R, BRODERICK J P, CAMPBELL B C, et al . The Heidelberg bleeding classification: classification of bleeding events after ischemic stroke and reperfusion therapy[J ] . Stroke, 2015, 46(10): 2981-2986. DOI: 10.1161/strokeaha.115.010049.
KARSY M, BROCK A, GUAN J, et al . Neuroprotective strategies and the underlying molecular basis of cerebro-vascular stroke[J ] . Neurosurg Focus, 2017, 42(4): E3. DOI: 10.3171/2017.1.focus16522.
CHAMORRO Á, DIRNAGL U, URRA X, et al . Neuroprotection in acute stroke: targeting excitotoxicity, oxidative and nitrosative stress, and inflammation[J ] . Lancet Neurol, 2016, 15(8): 869-881. DOI: 10.1016/s1474-4422(16)00114-9.
CHEN X Q, QIU K, LIU H, et al . Application and prospects of butylphthalide for the treatment of neurologic diseases[J ] . Chin Med J (Engl), 2019, 132(12): 1467-1477. DOI: 10.1097/cm9.0000000000000289.
YAN R Y, WANG S J, YAO G T, et al . The protective effect and its mechanism of 3-n-butylphthalide pretreatment on cerebral ischemia reperfusion injury in rats[J ] . Eur Rev Med Pharmacol Sci, 2017, 21(22): 5275-5282. DOI: 10.26355/eurrev_201711_13852.
DIAO X, DENG P, XIE C, et al . Metabolism and pharmacokinetics of 3-n-butylphthalide (NBP) in humans: the role of cytochrome P450s and alcohol dehydrogenase in biotransformation[J ] . Drug Metab Dispos, 2013, 41(2): 430-444. DOI: 10.1124/dmd.112.049684.
CHONG Z Z, FENG Y P. Effects of dl-3-n-butylphthalide on production of TXB2 and 6-keto-PGF 1 alpha in rat brain during focal cerebral ischemia and reperfusion[J ] . Acta Pharmacologica Sinica, 1997, 18(6): 505-508.
TANG S C, LUO C J, ZHANG K H, et al . Effects of dl-3-n-butylphthalide on serum VEGF and bFGF levels in acute cerebral infarction[J ] . Eur Rev Med Pharmacol Sci, 2017, 21(19): 4431-4436.
CHEN N, ZHOU Z, LI J, et al . 3-n-butylphthalide exerts neuroprotective effects by enhancing anti-oxidation and attenuating mitochondrial dysfunction in an in vitro model of ischemic stroke[J ] . Drug Des Devel Ther, 2018, 12: 4261-4271. DOI: 10.2147/dddt.s189472..
ZHANG X L, DONG Y T, LIU Y, et al . Effects of dl-3-n-butylphthalide on serum lipoprotein-associated phospholipase A2 and hypersensitive C-reactive protein levels in acute cerebral infarction[J ] . Brain Behav, 2019, 9(12): e01469. DOI: 10.1002/brb3.1469.
LAN Z, XU X, XU W, et al . Discovery of 3-n-butyl-2, 3-dihydro-1H-isoindol-1-one as a potential anti-ischemic stroke agent[J ] . Drug Des Devel Ther, 2015, 9: 3377-3391. DOI: 10.2147/dddt.s84731.
李凤, 杨璟, 王攀, 等.丁苯酞对进展性脑梗死患者血清MMP-9、MMP-2及神经功能的影响[J].中国新药与临床杂志, 2019, 38(8): 477-481.
LI F, YANG J, WANG P, et al . Effects of butylphthalide on levels of serum MMP-9, MMP-2 and neurological function in patients with progressive infarction[J ] . Chin J New Drugs Clin Remedies, 2019, 38(8): 477-481.
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