缺血性卒中血栓切除术前使用替奈普酶和阿替普酶的比较 - NEJM医学前沿
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缺血性卒中血栓切除术前使用替奈普酶和阿替普酶的比较
Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke


Bruce C.V. Campbell ... 心脑血管疾病 • 2018.04.26
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• 替奈普酶是急性缺血性卒中的优选溶栓药吗

替奈普酶——缺血性卒中桥接治疗的新武器

 

王伊龙

首都医科大学附属北京天坛医院

 

目前为止,阿替普酶是唯一一种被批准的治疗急性缺血性卒中的静脉溶栓药物,但是,科学家们探索新型溶栓药物的脚步始终没有停止。此前有一些研究显示出了有更长半衰期的替奈普酶可以通过推注1次给药,更快捷,再通率可能更高1,2,而2018年4月26日发表在《新英格兰医学杂志》上的EXTEND-IA TNK研究又提供了新的证据3

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摘要


背景

缺血性卒中血管内血栓切除术前可静脉输注阿替普酶用于溶栓。替奈普酶比阿替普酶的纤维蛋白特异性更强且活性持续时间更长,通过静脉推注给药,可能增加血管再灌注的发生率。

 

方法

本研究对缺血性卒中患者进行随机分组,这些患者有颈内动脉、基底动脉或大脑中动脉闭塞并适合接受血栓切除术,随机分配这些患者在症状发生后4.5小时内接受替奈普酶(剂量为0.25 mg/kg;最大剂量为25 mg)或阿替普酶(剂量为0.9 mg/kg;最大剂量为90 mg)治疗。主要结局是在初始血管造影评估时,受累缺血区域再灌注大于50%或没有可取出的血栓。研究检验了替奈普酶的非劣效性,其次是优效性。次要结局包括90日时的改良Rankin量表评分(量表范围从0 [无神经功能缺损] ~6分 [死亡])。安全性结局是死亡和有症状的脑内出血。

 

结果

本研究共纳入了202例患者,其中101例接受替奈普酶治疗,101例接受阿替普酶治疗。主要结局在接受替奈普酶和阿替普酶治疗的患者中发生率分别为22%和10%(发生率差异,12个百分点;95%置信区间[CI],2~21;发生率比,2.2;95% CI,1.1~4.4;非劣效性P=0.002;优效性P=0.03)。替奈普酶治疗组的90日功能性结局优于阿替普酶组(中位改良Rankin量表评分,2 分vs. 3分;常用比值比,1.7;95% CI,1.0~2.8;P=0.04)。每组有1%的患者出现有症状的脑内出血。

 

结论

缺血性卒中患者在症状发生后4.5小时内治疗时,在血栓切除术前进行替奈普酶治疗的再灌注率和功能结局优于阿替普酶(由澳大利亚国家健康与医学研究委员会等资助;EXTEND-IA TNK在ClinicalTrials.gov注册号为NCT02388061)。





作者信息

Bruce C.V. Campbell, Ph.D., Peter J. Mitchell, M.Med., Leonid Churilov, Ph.D., Nawaf Yassi, Ph.D., Timothy J. Kleinig, Ph.D., Richard J. Dowling, M.B., B.S., Bernard Yan, M.B., B.S., Steven J. Bush, M.B., B.S., Helen M. Dewey, M.D., Vincent Thijs, M.D., Rebecca Scroop, M.B., B.S., Marion Simpson, M.B., B.S., et al., for the EXTEND-IA TNK Investigators*
From the Departments of Medicine and Neurology, Melbourne Brain Centre (B.C.V.C., N.Y., B.Y., T.Y.W., D.G.S., E.R., H.Z., P.S., G.S., M.W.P., S.M.D.), and the Department of Radiology (P.J.M., R.J.D., S.J.B., P.M.D.), Royal Melbourne Hospital, and the Florey Institute of Neuroscience and Mental Health (L.C., N.Y., V.T., H.A., H.M., C.F.B., G.A.D.), University of Melbourne, Parkville, VIC, the Departments of Neurology (T.J.K.) and Radiology (R.S.), Royal Adelaide Hospital, and the Department of Neurology, Lyell McEwin Hospital (D.F.), Adelaide, SA, the Department of Neurosciences, Eastern Health and Eastern Health Clinical School (H.M.D., C.F.B.), and the Departments of Neurology (H.M., T.G.P.) and Radiology (W. Chong, R.V.C., L.-A.S.), Monash Medical Centre, Monash University, Clayton, VIC, the Departments of Neurology (V.T., M.S.) and Radiology (M.B., H.A.), Austin Hospital, Austin Health, Heidelberg, VIC, School of Medicine, Faculty of Health, Deakin University, Melbourne, VIC (H.A.), and the Departments of Medicine and Neurology, Melbourne Medical School, University of Melbourne and Western Health, Sunshine Hospital, St. Albans, VIC (T.W.), the Departments of Neurology (D.G.S., H.B.) and Radiology (K.R., D.L.), Princess Alexandra Hospital, and the Departments of Neurology (A.A.W., C.M.) and Radiology (A.C., K. Mitchell, J.C., K. Mahady), Royal Brisbane and Women’s Hospital and the University of Queensland, Brisbane, the Departments of Neurology (P.B.) and Radiology (H.R., L.V.), Gold Coast University Hospital, Southport, QLD, and the Department of Neurology, Priority Research Centre for Brain and Mental Health Research, John Hunter Hospital, University of Newcastle, Newcastle, NSW (T.A., F.M., C.R.L., C.G.-E., M.W.P.), the Department of Neurology, Royal North Shore Hospital and Kolling Institute, University of Sydney (M.K.), and the Department of Radiology, Royal North Shore Hospital (T.J.H., K.C.F., B.S.S.), St. Leonards, and the Department of Radiology, Westmead Hospital, Sydney (T.J.H., K.C.F., B.S.S.) — all in Australia; and the Departments of Neurology (T.Y.W., J.N.F.) and Radiology (W. Collecutt), Christchurch Hospital, Christchurch, New Zealand. Address reprint requests to Dr. Campbell at the Department of Neurology, Royal Melbourne Hospital, 300 Grattan St., Parkville, VIC 3050, Australia, or at bruce.campbell@mh.org.au. *A list of the investigators in the EXTEND-IA TNK trial is provided in the Supplementary Appendix, available at NEJM.org.

 

参考文献

1. Powers WJ, Rabinstein AA, Ackerson T, et al. 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. Stroke 2018;49(3):e46-e110.

2. Goyal M, Menon BK, van Zwam WH, et al. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet 2016;387:1723-1731.

3. Campbell BC, Mitchell PJ, Kleinig TJ, et al. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med 2015;372:1009-1018.

4. Saver JL, Goyal M, Bonafe A, et al. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med 2015;372:2285-2295.

5. Goyal M, Demchuk AM, Menon BK, et al. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med 2015;372:1019-1030.

6. Tanswell P, Modi N, Combs D, Danays T. Pharmacokinetics and pharmacodynamics of tenecteplase in fibrinolytic therapy of acute myocardial infarction. Clin Pharmacokinet 2002;41:1229-1245.

7. Van De Werf F, Adgey J, Ardissino D, et al. Single-bolus tenecteplase compared with front-loaded alteplase in acute myocardial infarction: the ASSENT-2 double-blind randomised trial. Lancet 1999;354:716-722.

8. Parsons M, Spratt N, Bivard A, et al. A randomized trial of tenecteplase versus alteplase for acute ischemic stroke. N Engl J Med 2012;366:1099-1107.

9. Huang X, Cheripelli BK, Lloyd SM, et al. Alteplase versus tenecteplase for thrombolysis after ischaemic stroke (ATTEST): a phase 2, randomised, open-label, blinded endpoint study. Lancet Neurol 2015;14:368-376.

10. Logallo N, Novotny V, Assmus J, et al. Tenecteplase versus alteplase for management of acute ischaemic stroke (NOR-TEST): a phase 3, randomised, open-label, blinded endpoint trial. Lancet Neurol 2017;16:781-788.

11. Hansson L, Hedner T, Dahlöf B. Prospective randomized open blinded end-point (PROBE) study: a novel design for intervention trials: Prospective Randomized Open Blinded End-Point. Blood Press 1992;1:113-119.

12. Campbell BC, Mitchell PJ, Churilov L, et al. Tenecteplase versus alteplase before endovascular thrombectomy (EXTEND-IA TNK): a multicenter, randomized, controlled study. Int J Stroke 2018;13:328-334.

13. Campbell BCV, Majoie CBLM, Hill MD, et al. CT perfusion imaging profiles and response to endovascular reperfusion in pooled analysis of randomized trials of endovascular stent thrombectomy. Eur Stroke J 2016;1:Suppl:635-635. abstract.

14. Wintermark M, Albers GW, Broderick JP, et al. Acute stroke imaging research roadmap II. Stroke 2013;44:2628-2639.

15. Wahlgren N, Ahmed N, Dávalos A, et al. Thrombolysis with alteplase for acute ischaemic stroke in the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST): an observational study. Lancet 2007;369:275-282.

16. Mehta CR, Pocock SJ. Adaptive increase in sample size when interim results are promising: a practical guide with examples. Stat Med 2011;30:3267-3284.

17. Zou G. A modified Poisson regression approach to prospective studies with binary data. Am J Epidemiol 2004;159:702-706.

18. Churilov L, Arnup S, Johns H, et al. An improved method for simple, assumption-free ordinal analysis of the modified Rankin Scale using generalized odds ratios. Int J Stroke 2014;9:999-1005.

19. Howard G, Waller JL, Voeks JH, et al. A simple, assumption-free, and clinically interpretable approach for analysis of modified Rankin outcomes. Stroke 2012;43:664-669.

20. Emberson J, Lees KR, Lyden P, et al. Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials. Lancet 2014;384:1929-1935.

21. Saver JL, Goyal M, van der Lugt A, et al. Time to treatment with endovascular thrombectomy and outcomes from ischemic stroke: a meta-analysis. JAMA 2016;316:1279-1288.

22. Chia NH, Leyden JM, Newbury J, Jannes J, Kleinig TJ. Determining the number of ischemic strokes potentially eligible for endovascular thrombectomy: a population-based study. Stroke 2016;47:1377-1380.

23. Malhotra K, Gornbein J, Saver JL. Ischemic strokes due to large-vessel occlusions contribute disproportionately to stroke-related dependence and death: a review. Front Neurol 2017;8:651-651.

24. Bivard A, Huang X, Levi CR, et al. Tenecteplase in ischemic stroke offers improved recanalization: analysis of 2 trials. Neurology 2017;89:62-67.

25. Haley EC Jr, Thompson JL, Grotta JC, et al. Phase IIB/III trial of tenecteplase in acute ischemic stroke: results of a prematurely terminated randomized clinical trial. Stroke 2010;41:707-711.

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