中风治疗-血栓清除术

The new england journal of medicine

Stent-Retriever Thrombectomy after Intravenous

t-PA vs. t-PA Alone in Stroke

Jeffrey L. Saver, M.D., Mayank Goyal, M.D., Alain Bonafe, M.D.,

Hans-Christoph Diener, M.D., Ph.D., Elad I. Levy, M.D., Vitor M. Pereira, M.D.,

Gregory W. Albers, M.D., Christophe Cognard, M.D., David J. Cohen, M.D.,

Werner Hacke, M.D., Ph.D., Olav Jansen, M.D., Ph.D., Tudor G. Jovin, M.D.,

Heinrich P. Mattle, M.D., Raul G. Nogueira, M.D., Adnan H. Siddiqui, M.D., Ph.D.,

Dileep R. Yavagal, M.D., Blaise W. Baxter, M.D., Thomas G. Devlin, M.D., Ph.D.,

Demetrius K. Lopes, M.D., Vivek K. Reddy, M.D., Richard du Mesnil de Rochemont, M.D.,

Oliver C. Singer, M.D., and Reza Jahan, M.D., for the SWIFT PRIME Investigators*

ABSTRACT

BACKGROUND

Among patients with acute ischemic stroke due to occlusions in the proximal ante-rior intracranial circulation, less than 40% regain functional independence when treated with intravenous tissue plasminogen activator (t-PA) alone. Thrombectomy with the use of a stent retriever, in addition to intravenous t-PA, increases reperfu-sion rates and may improve long-term functional outcome.

METHODSThe authors’ affiliations are listed in the Appendix. Address reprint requests to Dr. Saver at the UCLA Stroke Center, 710 Westwood Plaza, Los Angeles, CA 90095, or at jsaver@mednet.ucla.edu.Drs. Saver and Goyal contributed equally to this article.

*A complete list of investigators in the

Solitaire with the Intention for Throm-

bectomy as Primary Endovascular Treat-

ment (SWIFT PRIME) trial is provided in

the Supplementary Appendix, available at

http://wendang.chazidian.com.

This article was published on April 17,

2015, at http://wendang.chazidian.com.

DOI: 10.1056/NEJMoa1415061Copyright © 2015 Massachusetts Medical Society.We randomly assigned eligible patients with stroke who were receiving or had re-ceived intravenous t-PA to continue with t-PA alone (control group) or to undergo endovascular thrombectomy with the use of a stent retriever within 6 hours after symptom onset (intervention group). Patients had confirmed occlusions in the proxi-mal anterior intracranial circulation and an absence of large ischemic-core lesions. The primary outcome was the severity of global disability at 90 days, as assessed by means of the modified Rankin scale (with scores ranging from 0 [no symptoms] to 6 [death]).

RESULTS

The study was stopped early because of efficacy. At 39 centers, 196 patients under-went randomization (98 patients in each group). In the intervention group, the median time from qualifying imaging to groin puncture was 57 minutes, and the rate of substantial reperfusion at the end of the procedure was 88%. Thrombectomy with the stent retriever plus intravenous t-PA reduced disability at 90 days over the entire range of scores on the modified Rankin scale (P<0.001). The rate of func-tional independence (modified Rankin scale score, 0 to 2) was higher in the inter-vention group than in the control group (60% vs. 35%, P<0.001). There were no significant between-group differences in 90-day mortality (9% vs. 12%, P = 0.50) or symptomatic intracranial hemorrhage (0% vs. 3%, P = 0.12).

CONCLUSIONS

In patients receiving intravenous t-PA for acute ischemic stroke due to occlusions in the proximal anterior intracranial circulation, thrombectomy with a stent retriever within 6 hours after onset improved functional outcomes at 90 days. (Funded by Covidien; SWIFT PRIME ClinicalTrials.gov number, NCT01657461.)

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Intravenous tissue plasminogen acti-METHODSvator (t-PA) administered within 4.5 hours after the onset of acute ischemic stroke im-TRIAL DESIGN

proves outcomes.1-3 However, intravenous t-PA has In this international, multicenter, prospective, multiple constraints, including unresponsiveness randomized, open clinical trial, we compared in-of large thrombi to rapid enzymatic digestion, a travenous t-PA followed by neurovascular throm-narrow time window for administration, and the bectomy with the use of a stent retriever with risk of cerebral and systemic hemorrhage. Among intravenous t-PA alone in patients with acute is-patients with occlusions of the intracranial inter-chemic stroke. All the patients had confirmed oc-nal carotid artery or the first segment of the clusion of the intracranial internal carotid artery, middle cerebral artery (or both), intravenous t-PA the first segment of the middle cerebral artery, or results in early reperfusion in only 13 to 50%.4-7both on vessel imaging and an absence of large Neurovascular thrombectomy is a reperfusion ischemic-core lesions. Patients were randomly strategy that is distinct from pharmacologic fibri-assigned in a 1:1 ratio to one of two treatment nolysis. Endovascular mechanical treatments can groups: intravenous t-PA plus stent retriever (in-remove large, proximal clots rapidly and result in tervention group) or intravenous t-PA alone (con-higher rates of reperfusion than intravenous t-PA trol group). Using a minimization algorithm, alone. Three initial trials of endovascular thera-we balanced the numbers of patients in the two pies did not show a benefit for thrombectomy treatment groups with respect to four factors: over intravenous t-PA or supportive medical care, investigational site, baseline severity according but they were limited by the use of intraarterial to the National Institutes of Health Stroke Scale delivery of t-PA or the use of early-generation de-(NIHSS) score (≤17 vs. >17, on a scale of 0 to 42, vices with modest reperfusion efficacy (or both), with higher scores indicating greater severity), age the failure of two trials to use vessel imaging to (<70 years vs. ≥70 years), and occlusion location confirm the presence of an appropriate target oc-(middle cerebral artery vs. internal carotid artery).clusion, and the slow initiation of endovascular Details of the study design have been pub-intervention.8-10lished previously.19 The study was conducted and The Solitaire revascularization device (Covidien) reported with fidelity to the study protocol, avail-is a self-expanding stent used to retrieve thrombi able with the full text of this article at http://wendang.chazidian.com. and restore blood flow. In multicenter registries (An overview of the study procedure is provided and one randomized trial, this stent retriever, in Fig. S1 in the Supplementary Appendix, avail-as compared with early-generation mechanical able at http://wendang.chazidian.com.)thrombectomy devices, was associated with fast-The trial was approved by the institutional er and more frequent reperfusion, reduced intra-review board at each site. Enrolled patients pro-cranial hemorrhage, and improved disability vided written informed consent, or at select sites, outcome.11-15there was an exception from explicit informed We performed the Solitaire with the Intention consent in emergency circumstances.for Thrombectomy as Primary Endovascular Treat-The trial was funded by Covidien and designed ment (SWIFT PRIME) trial to establish the effi-and led by a steering committee that included cacy and safety of rapid neurovascular throm-academic investigators and representatives of the bectomy with the stent retriever in conjunction sponsor. The site investigators gathered the data, with intravenous t-PA versus intravenous t-PA alone with monitoring and database maintenance per-in patients with acute ischemic stroke. This trial formed by the sponsor. The first and subsequent was among several contemporaneous trials drafts of the manuscript were written by the launched worldwide to test new-generation strat-first and second authors, incorporating input egies for mechanical thrombectomy.16-18 Our from all the authors. The academic authors had trial was conducted in multiple countries and unrestricted access to the data, performed the health systems as a registration trial capable of data analysis with the primary and the indepen-supporting expansion of regulatory labeling. We dent study statisticians, and attest to the integ-used a uniform device procedure in the interven-rity of the trial and the completeness and accu-tion group and tested intracranial neurovascular racy of the reported data. The trial was monitored thrombectomy alone rather than in combination by an independent data and safety monitoring with cervical stenting.board.

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Stent Retriever after Intravenous t-PA vs. t-PA Alone

procedure performance. The study target for the

The study was performed at 39 centers in the time from qualifying imaging to groin puncture United States and Europe. All study centers were was within 70 minutes.

required to have performed at least 40 mechani-cal-thrombectomy procedures, including at least OUTCOME MEASURES

20 procedures with the Solitaire stent retriever, The primary study-outcome measure was disabil-annually. Entry criteria selected patients who had ity at 90 days, as assessed by means of the modi-acute ischemic stroke with moderate-to-severe fied Rankin scale, a global measure of disability neurologic deficits; had imaging-confirmed oc-on a seven-level scale, with scores ranging from clusion of the intracranial internal carotid artery, 0 (no symptoms) to 6 (death) (Fig. 1). (Details on the first segment of the middle cerebral artery, or the use of this scale are provided in the Supple-both; met the imaging eligibility requirements; mentary Appendix.)Secondary clinical efficacy outcomes were the were receiving or had received intravenous t-PA; and were able to undergo initiation of endovas-rate of death at 90 days, the rate of functional cular treatment within 6 hours after the time independence (modified Rankin scale score, ≤2) that they were last known to be well before the at 90 days, and the change in the NIHSS score onset of acute stroke symptoms. Qualifying im-at 27 hours after randomization. The technical aging had to be performed at a study hospital; im-efficacy outcomes regarding revascularization were aging was repeated for patients who were trans-substantial reperfusion, as assessed by means of ferred from outside hospitals. Detailed study catheter angiography in the intervention group inclusion and exclusion criteria are provided in and defined as a modified Thrombolysis in Ce-

Table S1 in the Supplementary Appendix.To identify patients with salvageable tissue, at trial launch the entry criteria regarding imaging selection required patients to have a target-mis-match penumbral profile, with a small core of tissue that was likely to be irreversibly injured and a large region of hypoperfused tissue that was likely to be salvageable. Penumbral imaging analysis was performed with the use of RAPID (iSchemaView), an operator-independent image-postprocessing system.20 After the enrollment of the first 71 patients, these criteria were revised to use a small-to-moderate core-infarct strategy (Table S1 in the Supplementary Appendix) to ac-commodate study sites with limited perfusion-imaging capability and to ensure accelerated treat-ment delivery. Study sites with advanced imaging capability were still encouraged to obtain pen-umbral imaging and to exclude patients who did not meet the target-mismatch profile.PATIENTS AND PARTICIPATING CENTERS

INTERVENTION

In the intervention group, neurovascular throm-bectomy was performed with the use of the Soli-taire FR (Flow Restoration) or Solitaire 2 device. Concomitant stenting of the cervical internal ca-rotid artery was not permitted, although angioplas-ty could be performed to permit intracranial access.A studywide continuous quality-improvement program emphasized the speed and quality of the neurointerventional workflow, including rapid pa-tient transfer to the neuroangiography suite and n engl j med http://wendang.chazidian.com3

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rebral Infarction score of 2b (50 to 99% reperfu-sion) or 3 (complete reperfusion)21; and successful reperfusion at 27 hours in the two study groups, which was defined as reperfusion of 90% or more of the initial perfusion-lesion volume, as assessed by means of perfusion imaging (com-puted tomography [CT] or magnetic resonance imaging [MRI]) at 27 hours after randomiza-tion. Prespecified safety outcomes were all seri-ous adverse events through study completion and symptomatic intracranial hemorrhage at 27 hours after randomization.

CLINICAL AND RADIOLOGIC ASSESSMENT

Clinical assessments were performed at baseline, 27 hours after randomization, 7 to 10 days (or at discharge if earlier), 30 days, and 90 days. Clini-cal evaluations included the score on the modi-fied Rankin scale for assessing global disability and the NIHSS score for assessing neurologic deficit. Entry and outcome neurovascular images were assessed in a blinded manner by staff at the core imaging laboratories (iSchemaView for pen-umbral and volumetric imaging and Synarc for

parenchymal and angiographic imaging).

4

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Stent Retriever after Intravenous t-PA vs. t-PA Alone

* Plus–minus values are means ±SD. There were no significant differences between the two groups. One patient in the group that received intravenous tissue plasminogen activator (t-PA) alone requested the deletion of all data. Three additional patients in the group that received intravenous t-PA alone (1 patient who died and 2 who withdrew) are missing some baseline data owing to early study exit, including data on the prestroke modified Rankin Scale score, the hospital site of intravenous t-PA administration, and site of intracranial-artery occlusion for all 3 patients, and data on sex, race, and ethnic group for 1. Data on race and ethnic group were missing for all 13 patients in France owing to national regulations. Data regarding the location of the arterial occlusion were missing for 7 patients be-cause the core laboratory considered that imaging could not be assessed with complete reliability. Two patients were deemed by the core laboratory to not have occlusions in the internal carotid artery or the first or second segment of the middle cerebral artery. A total of 37 patients did not have baseline penumbral imaging performed, after a protocol amendment making penumbral imaging optional. Data regarding additional baseline characteristics are shown in Table S4 in the Supplementary Appendix. NA denotes not applicable.? Race and ethnic group were self-reported.? Scores on the National Institutes of Health Stroke Scale (NIHSS) range from 0 to 42, with higher scores indicating more severe neurologic deficit.§ Scores on the modified Rankin scale for the assessment of global disability range from 0 (no symptoms) to 6 (death).¶ To convert the values for glucose to millimoles per liter, multiply by 0.05551.‖ The Alberta Stroke Program Early CT Score (ASPECTS) ranges from 0 to 10, with higher scores indicating a smaller infarct core.** The target-mismatch profile was defined as meeting the following criteria as assessed on CT perfusion or diffusion imaging and perfusion MRI: the core infarct lesion measured 50 ml or less, the volume of tissue with a time to maxi-mum delay of more than 10 seconds was 100 ml or less, and the mismatch volume was at least 15 ml and the mis-match ratio was more than 1.8:1.0.?? These occlusions were classified as first-segment occlusions by the treating site at the time of study entry but as sec-ond-segment occlusions by the core imaging laboratory.

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