Time to Reperfusion and Treatment Effect for Acute Ischemic Stroke A Randomized Clinical Trial

被引：202

作者：

Fransen, Puck S. S. ^{[1
,2
]}

Berkhemer, Olvert A. ^{[1
,3
]}

Lingsma, Hester F. ^{[4
,44
,45
]}

Beumer, Debbie ^{[5
]}

van den Berg, Lucie A. ^{[6
]}

Yoo, Albert J. ^{[7
,46
]}

Schonewille, Wouter J. ^{[8
]}

Vos, Jan Albert ^{[9
]}

Nederkoorn, Paul J. ^{[6
]}

Wermer, Marieke J. H. ^{[10
]}

van Walderveen, Marianne A. A.

Staals, Julie ^{[5
]}

Hofmeijer, Jeannette ^{[11
,51
]}

van Oostayen, Jacques A. ^{[12
]}

Nijeholt, Geert J. Lycklama a ^{[13
]}

Boiten, Jelis ^{[14
]}

Brouwer, Patrick A. ^{[2
]}

Emmer, Bart J. ^{[2
]}

de Bruijn, Sebastiaan F. ^{[15
]}

van Dijk, Lukas C.

Kappelle, L. Jaap ^{[17
]}

Lo, Rob H. ^{[18
]}

van Dijk, Ewoud J. ^{[16
,19
,35
]}

de Vries, Joost ^{[20
]}

de Kort, Paul L. M. ^{[21
]}

van den Berg, J. S. Peter ^{[22
]}

van Hasselt, Boudewijn A. A. M. ^{[23
,36
]}

Aerden, Leo A. M. ^{[24
]}

Dallinga, Rene J. ^{[25
,38
]}

Visser, Marieke C. ^{[26
]}

Bot, Joseph C. J. ^{[27
,39
]}

Vroomen, Patrick C. ^{[28
]}

Eshghi, Omid ^{[29
]}

Schreuder, Tobien H. C. M. L. ^{[30
]}

Heijboer, Roel J. J. ^{[31
,37
]}

Keizer, Koos ^{[32
]}

Tielbeek, Alexander V. ^{[33
,34
]}

den Hertog, Heleen M.

Gerrits, Dick G. ^{[40
,52
]}

van den Berg-Vos, Renske M. ^{[48
]}

Karas, Giorgos B. ^{[49
,50
]}

Steyerberg, Ewout W. ^{[4
]}

Flach, H. Zwenneke ^{[24
,41
]}

Marquering, Henk A. ^{[3
,42
,43
,53
]}

Sprengers, Marieke E. S. ^{[3
]}

Jenniskens, Sjoerd F. M. ^{[47
,54
]}

Beenen, Ludo F. M.

van den Berg, Rene

Koudstaal, Peter J. ^{[1
]}

van Zwam, Wim H.

机构：

[1] Erasmus MC, Univ Med Ctr Rotterdam, Dept Neurol, Room H643,POB 2040, NL-3000 CA Rotterdam, Netherlands

[2] Erasmus MC, Univ Med Ctr Rotterdam, Dept Radiol, Rotterdam, Netherlands

[3] Acad Med Ctr, Dept Radiol, Amsterdam, Netherlands

[4] Erasmus MC, Univ Med Ctr Rotterdam, Dept Publ Hlth, Rotterdam, Netherlands

[5] Maastricht Univ, Med Ctr, Dept Neurol, Cardiovasc Res Inst Maastricht, Maastricht, Netherlands

[6] Acad Med Ctr, Dept Neurol, Amsterdam, Netherlands

[7] Texas Stroke Inst, Plano, TX USA

[8] St Antonius Hosp, Dept Neurol, Nieuwegein, Netherlands

[9] St Antonius Hosp, Dept Radiol, Nieuwegein, Netherlands

[10] Leiden Univ, Med Ctr, Dept Neurol, Leiden, Netherlands

[11] Rijnstate Hosp, Dept Neurol, Arnhem, Netherlands

[12] Rijnstate Hosp, Dept Radiol, Arnhem, Netherlands

[13] Med Ctr Haaglanden, Dept Radiol, The Hague, Netherlands

[14] Med Ctr Haaglanden, Dept Neurol, The Hague, Netherlands

[15] Haga Hosp, Dept Neurol, The Hague, Netherlands

[16] Haga Hosp, Dept Radiol, The Hague, Netherlands

[17] Univ Med Ctr Utrecht, Dept Neurol, Utrecht, Netherlands

[18] Univ Med Ctr Utrecht, Dept Radiol, Utrecht, Netherlands

[19] Radboud Univ Nijmegen, Med Ctr, Dept Neurol, Nijmegen, Netherlands

[20] Radboud Univ Nijmegen, Med Ctr, Dept Neurosurg, Nijmegen, Netherlands

[21] St Elizabeth Hosp, Dept Neurol, Tilburg, Netherlands

[22] Isala Klin, Dept Neurol, Zwolle, Netherlands

[23] Isala Klin, Dept Radiol, Zwolle, Netherlands

[24] Reinier Graaf Gasthuis, Dept Neurol, Delft, Netherlands

[25] Reinier Graaf Gasthuis, Dept Radiol, Delft, Netherlands

[26] Vrije Univ Amsterdam Med Ctr, Dept Neurol, Amsterdam, Netherlands

[27] Vrije Univ Amsterdam Med Ctr, Dept Radiol, Amsterdam, Netherlands

[28] Univ Groningen, Univ Med Ctr Groningen, Dept Neurol, Groningen, Netherlands

[29] Univ Groningen, Univ Med Ctr Groningen, Dept Radiol, Groningen, Netherlands

[30] Atrium Med Ctr, Dept Neurol, Heerlen, Netherlands

[31] Atrium Med Ctr, Dept Radiol, Heerlen, Netherlands

[32] Catharina Hosp, Dept Neurol, Eindhoven, Netherlands

[33] Catharina Hosp, Dept Radiol, Eindhoven, Netherlands

[34] Med Spectrum Ctr Groningen, Dept Neurol, Eindhoven, Netherlands

[35] Catharina Hosp, Dept Radiol, Eindhoven, Netherlands

[36] Haga Hosp, Dept Radiol, The Hague, Netherlands

[37] Isala Klin, Dept Radiol, Zwolle, Netherlands

[38] Atrium Med Ctr, Dept Radiol, Heerlen, Netherlands

[39] Reinier Graaf Gasthuis, Dept Radiol, Delft, Netherlands

[40] Vrije Univ Amsterdam Med Ctr, Dept Radiol, Amsterdam, Netherlands

[41] Med Spectrum Twente, Dept Radiol, Enschede, Netherlands

[42] Erasmus MC Univ, Med Ctr Rotterdam, Dept Neurol & Radiol, Rotterdam, Netherlands

[43] Erasmus MC, Univ Med Ctr Rotterdam, Dept Radiol, Rotterdam, Netherlands

[44] Acad Med Ctr, Dept Radiol, Amsterdam, Netherlands

[45] Acad Med Ctr, Dept Biomed Engn & Phys, Amsterdam, Netherlands

[46] Erasmus MC, Univ Med Ctr, Dept Publ Hlth, Rotterdam, Netherlands

[47] Texas Stroke Inst, Plano, TX USA

[48] Radboud Univ Nijmegen, Med Ctr, Dept Radiol, Nijmegen, Netherlands

[49] St Lucas Andreas Hosp, Dept Neurol, Amsterdam, Netherlands

[50] St Lucas Andreas Hosp, Dept Radiol, Amsterdam, Netherlands

来源：

JAMA NEUROLOGY | 2016年 / 73卷 / 02期

关键词：

INTRAVENOUS T-PA; ENDOVASCULAR TREATMENT; ANGIOGRAPHIC REPERFUSION; THROMBECTOMY; THERAPY; INTERVENTION; COMPLEXITY; OUTCOMES;

D O I：

10.1001/jamaneurol.2015.3886

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

IMPORTANCE Intra-arterial treatment (IAT) for acute ischemic stroke caused by intracranial arterial occlusion leads to improved functional outcome in patients treated within 6 hours after onset. The influence of treatment delay on treatment effect is not yet known. OBJECTIVE To evaluate the influence of time from stroke onset to the start of treatment and from stroke onset to reperfusion on the effect of IAT. DESIGN, SETTING, AND PARTICIPANTS The Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands (MR CLEAN) was a multicenter, randomized clinical open-label trial of IAT vs no IAT in 500 patients. The time to the start of treatment was defined as the time from onset of symptoms to groin puncture (TOG). The time from onset of treatment to reperfusion (TOR) was defined as the time to reopening the vessel occlusion or the end of the procedure in cases for which reperfusion was not achieved. Data were collected from December 3, 2010, to June 3, 2014, and analyzed (intention to treat) from July 1, 2014, to September 19, 2015. MAIN OUTCOMES AND MEASURES Main outcome was the modified Rankin Scale (mRS) score for functional outcome (range, 0 [no symptoms] to 6 [death]). Multiple ordinal logistic regression analysis estimated the effect of treatment and tested for the interaction of time to randomization, TOG, and TOR with treatment. The effect of treatment as a risk difference on reaching independence (mRS score, 0-2) was computed as a function of TOG and TOR. Calculations were adjusted for age, National Institutes of Health Stroke Scale score, previous stroke, atrial fibrillation, diabetes mellitus, and intracranial arterial terminus occlusion. RESULTS Among 500 patients (58% male; median age, 67 years), the median TOG was 260 (interquartile range [IQR], 210-311) minutes; median TOR, 340 (IQR, 274-395) minutes. An interaction between TOR and treatment (P = .04) existed, but not between TOG and treatment (P = .26). The adjusted risk difference (95% CI) was 25.9% (8.3%-44.4%) when reperfusion was reached at 3 hours, 18.8% (6.6%-32.6%) at 4 hours, and 6.7% (0.4%-14.5%) at 6 hours. CONCLUSION AND RELEVANCE For every hour of reperfusion delay, the initially large benefit of IAT decreases; the absolute risk difference for a good outcome is reduced by 6% per hour of delay. Patients with acute ischemic stroke require immediate diagnostic workup and IAT in case of intracranial arterial vessel occlusion.

引用

页码：190 / 196

页数：7

共 20 条

[1] A Randomized Trial of Intraarterial Treatment for Acute Ischemic Stroke
Berkhemer, O. A.
Fransen, P. S. S.
Beumer, D.
van den Berg, L. A.
Lingsma, H. F.
Yoo, A. J.
Schonewille, W. J.
Vos, J. A.
Nederkoorn, P. J.
Wermer, M. J. H.
van Walderveen, M. A. A.
Staals, J.
Hofmeijer, J.
van Oostayen, J. A.
Nijeholt, G. J. Lycklama A.
Boiten, J.
Brouwer, P. A.
Emmer, B. J.
de Bruijn, S. F.
van Dijk, L. C.
Kappelle, L. J.
Lo, R. H.
Van Dijk, E. J.
de Vries, J.
de Kort, P. L. M.
van Rooij, W. J. J.
van den Berg, J. S. P.
van Hasselt, B. A. A. M.
Aerden, L. A. M.
Dallinga, R. J.
Visser, M. C.
Bot, J. C. J.
Vroomen, P. C.
Eshghi, O.
Schreuder, T. H. C. M. L.
Heijboer, R. J. J.
Keizer, K.
Tielbeek, A. V.
den Hertog, H. M.
Gerrits, D. G.
van den Berg-Vos, R. M.
Karas, G. B.
Steyerberg, E. W.
Flach, H. Z.
Marquering, H. A.
Sprengers, M. E. S.
Jenniskens, S. F. M.
Beenen, L. F. M.
van den Berg, R.
Koudstaal, P. J.
[J]. NEW ENGLAND JOURNAL OF MEDICINE, 2015, 372 (01) : 11 - 20
[2] Bracard S, 2015, 1 ANN EUR STROK ORG
[3] Endovascular Therapy after Intravenous t-PA versus t-PA Alone for Stroke
Broderick, Joseph P.
Palesch, Yuko Y.
Demchuk, Andrew M.
Yeatts, Sharon D.
Khatri, Pooja
Hill, Michael D.
Jauch, Edward C.
Jovin, Tudor G.
Yan, Bernard
Silver, Frank L.
von Kummer, Ruediger
Molina, Carlos A.
Demaerschalk, Bart M.
Budzik, Ronald
Clark, Wayne M.
Zaidat, Osama O.
Malisch, Tim W.
Goyal, Mayank
Schonewille, Wouter J.
Mazighi, Mikael
Engelter, Stefan T.
Anderson, Craig
Spilker, Judith
Carrozzella, Janice
Ryckborst, Karla J.
Janis, L. Scott
Martin, Renee H.
Foster, Lydia D.
Tomsick, Thomas A.
[J]. NEW ENGLAND JOURNAL OF MEDICINE, 2013, 368 (10) : 893 - 903
[4] Endovascular Therapy for Ischemic Stroke with Perfusion-Imaging Selection
Campbell, B. C. V.
Mitchell, P. J.
Kleinig, T. J.
Dewey, H. M.
Churilov, L.
Yassi, N.
Yan, B.
Dowling, R. J.
Parsons, M. W.
Oxley, T. J.
Wu, T. Y.
Brooks, M.
Simpson, M. A.
Miteff, F.
Levi, C. R.
Krause, M.
Harrington, T. J.
Faulder, K. C.
Steinfort, B. S.
Priglinger, M.
Ang, T.
Scroop, R.
Barber, P. A.
McGuinness, B.
Wijeratne, T.
Phan, T. G.
Chong, W.
Chandra, R. V.
Bladin, C. F.
Badve, M.
Rice, H.
de Villiers, L.
Ma, H.
Desmond, P. M.
Donnan, G. A.
Davis, S. M.
[J]. NEW ENGLAND JOURNAL OF MEDICINE, 2015, 372 (11) : 1009 - 1018
[5] Complexity of the endovascular intervention and clinical outcomes in acute ischaemic stroke
Ciccone, Alfonso
[J]. LANCET NEUROLOGY, 2014, 13 (09) : 865 - 865
[6] Ciccone A, 2013, NEW ENGL J MED, V368, P904, DOI [10.1056/NEJMoa1213701, 10.1056/NEJMc1304759]
[7] 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
Emberson, Jonathan
Lees, Kennedy R.
Lyden, Patrick
Blackwell, Lisa
Albers, Gregory
Bluhmki, Erich
Brott, Thomas
Cohen, Geoff
Davis, Stephen
Donnan, Geoffrey
Grotta, James
Howard, George
Kaste, Markku
Koga, Masatoshi
von Kummer, Ruediger
Lansberg, Maarten
Lindley, Richard I.
Murray, Gordon
Olivot, Jean Marc
Parsons, Mark
Tilley, Barbara
Toni, Danilo
Toyoda, Kazunori
Wahlgren, Nils
Wardlaw, Joanna
Whiteley, William
del Zoppo, Gregory J.
Baigent, Colin
Sandercock, Peter
Hacke, Werner
[J]. LANCET, 2014, 384 (9958) : 1929 - 1935
[8] MR CLEAN, a multicenter randomized clinical trial of endovascular treatment for acute ischemic stroke in the Netherlands: study protocol for a randomized controlled trial
Fransen, Puck S. S.
Beumer, Debbie
Berkhemer, Olvert A.
van den Berg, Lucie A.
Lingsma, Hester
van der Lugt, Aad
van Zwam, Wim H.
van Oostenbrugge, Robert J.
Roos, Yvo B. W. E. M.
Majoie, Charles B.
Dippel, Diederik W. J.
[J]. TRIALS, 2014, 15
[9] Randomized Assessment of Rapid Endovascular Treatment of Ischemic Stroke
Goyal, M.
Demchuk, A. M.
Menon, B. K.
Eesa, M.
Rempel, J. L.
Thornton, J.
Roy, D.
Jovin, T. G.
Willinsky, R. A.
Sapkota, B. L.
Dowlatshahi, D.
Frei, D. F.
Kamal, N. R.
Montanera, W. J.
Poppe, A. Y.
Ryckborst, K. J.
Silver, F. L.
Shuaib, A.
Tampieri, D.
Williams, D.
Bang, O. Y.
Baxter, B. W.
Burns, P. A.
Choe, H.
Heo, J. -H.
Holmstedt, C. A.
Jankowitz, B.
Kelly, M.
Linares, G.
Mandzia, J. L.
Shankar, J.
Sohn, S. -I.
Swartz, R. H.
Barber, P. A.
Coutts, S. B.
Smith, E. E.
Morrish, W. F.
Weill, A.
Subramaniam, S.
Mitha, A. P.
Wong, J. H.
Lowerison, M. W.
Sajobi, T. T.
Hill, M. D.
[J]. NEW ENGLAND JOURNAL OF MEDICINE, 2015, 372 (11) : 1019 - 1030
[10] Harrell FE, 2001, Regression Modeling Strategies: With Applications to Linear Models, Logistic Regression, and Survival Analysis

← 1 2 →