靜脈注射阿替普酶治療晚期影像學指導的腦卒中療效顯著
作者：
小柯機器人發布時間：2020/11/9 22:16:45
德國漢堡大學埃彭多夫附屬醫院Götz Thomalla團隊研究了靜脈注射阿替普酶治療晚期影像學指導的發病時間不明的腦卒中的療效。2020年11月8日，該研究發表在《柳葉刀》雜誌上。
患有中風且發病時間未知的患者此前被排除在溶栓治療之外。為了確定當使用影像學生物標誌物鑑定出可挽救的組織時，靜脈使用阿替普酶治療此類患者是否安全有效，研究組針對2020年9月21日之前發布的試驗，對單個患者的數據進行了系統回顧和薈萃分析。
研究組檢索灌注-擴散MRI、灌注CT或具有彌散加權成像流體衰減返轉恢復（DWI-FLAIR）不匹配，發病時間未知的中風成人患者，接受靜脈注射阿替普酶與標準治療或安慰劑的隨機試驗。主要結局為90天時的功能預後良好（改良Rankin量表[mRS]為0-1），表明無殘障。次要結局為90天時mRS向更好的功能結局和獨立結局（mRS 0–2）轉變。
在249個確定的摘要中，有四項試驗符合研究組的納入標準：WAKE-UP、EXTEND、THAWS和ECASS-4。這四項試驗提供了843位患者的個人數據，其中429位（51％）接受阿替普酶治療，414位（49％）接受安慰劑或標準治療。阿替普酶組420例患者中有199例（47％）預後較好，對照組409例患者中有160例（39％），組間差異顯著，且各研究間異質性較低。
阿替普酶組的患者向更好的功能結局和獨立結局轉變的可能性顯著高於對照組。阿替普酶組中有90名（21％）患者嚴重殘疾或死亡（mRS評分4-6），而對照組中有102名（25％），差異不顯著。阿替普酶組死亡27例（6％），對照組死亡14例（3％），差異顯著。阿替普酶組有症狀性顱內出血的發生率顯著高於對照組，分別為3％與不到1%。
研究結果表明，對於患有DWI-FLAIR或灌注不匹配的中風發作時間不明的患者，靜脈使用阿替普酶90天後的功能預後顯著優於安慰劑或標準治療。
附：英文原文
Title: Intravenous alteplase for stroke with unknown time of onset guided by advanced imaging: systematic review and meta-analysis of individual patient data
Author: Gtz Thomalla, Florent Boutitie, Henry Ma, Masatoshi Koga, Peter Ringleb, Lee H Schwamm, Ona Wu, Martin Bendszus, Christopher F Bladin, Bruce C V Campbell, Bastian Cheng, Leonid Churilov, Martin Ebinger, Matthias Endres, Jochen B Fiebach, Mayumi Fukuda-Doi, Manabu Inoue, Timothy J Kleinig, Lawrence L Latour, Robin Lemmens, Christopher R Levi, Didier Leys, Kaori Miwa, Carlos A Molina, Keith W Muir, Norbert Nighoghossian, Mark W Parsons, Salvador Pedraza, Peter D Schellinger, Stefan Schwab, Claus Z Simonsen, Shlee S Song, Vincent Thijs, Danilo Toni, Chung Y Hsu, Nils Wahlgren, Haruko Yamamoto, Nawaf Yassi, Sohei Yoshimura, Steven Warach, Werner Hacke, Kazunori Toyoda, Geoffrey A Donnan, Stephen M Davis, Christian Gerloff, Boris Raul Acosta, Karen Aegidius, Christian Albiker, Anna Alegiani, Miriam Almendrote, Angelika Alonso, Katharina Althaus, Pierre Amarenco, Hemasse Amiri, Bettina Anders, Adriana Aniculaesei, Jason Appleton, Juan Arenillas, Christina Back, Christian Bhr, Jürgen Bardutzky, Flore Baronnet-Chauvet, Rouven Bathe-Peters, Anna Bayer-Karpinska, Juan L. Becerra, Christoph Beck, Olga Belchí Guillamon, Amandine Benoit, Nadia Berhoune, Daniela Bindila, Julia Birchenall, Karine Blanc-Lasserre, Miguel Blanco Gonzales, Tobias Bobinger, Ulf Bodechtel, Eric Bodiguel, Urszula Bojaryn, Louise Bonnet, Benjamin Bouamra, Paul Bourgeois, Florent Boutitie, Lorenz Breuer, Ludovic Breynaert, David Broughton, Raf Brouns, Sébastian Brugirard, Bart Bruneel, Florian Buggle, Serkan Cakmak, Ana Calleja, David Calvet, David Carrera, Hsin-Chieh Chen
Issue&Volume: 2020-11-08
Abstract: Background
Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers.
Methods
We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0–1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0–2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4–6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903.
Findings
Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10–2·03]; p=0·011), with low heterogeneity across studies (I 2=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05–1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06–2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4–6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52–1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·03–4·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [<1%], adjusted OR 5·58 [1·22–25·50]; p=0·024).
Interpretation
In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death.
DOI: 10.1016/S0140-6736(20)32163-2
Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32163-2/fulltext