You are here

Article Text

Article menu

Download PDFPDF

Ischemic Stroke
Original research
Mechanical thrombectomy performs similarly in real world practice: a 2016 nationwide study from the Czech Republic
  1. Ondrej Volny1,2,
  2. Antonin Krajina3,
  3. Silvie Belaskova2,
  4. Michal Bar4,
  5. Petra Cimflova3,5,
  6. Roman Herzig6,
  7. Daniel Sanak7,
  8. Ales Tomek8,
  9. Martin Köcher9,
  10. Miloslav Rocek10,
  11. Radek Padr10,
  12. Filip Cihlar11,
  13. Miroslava Nevsimalova12,
  14. Lubomir Jurak13,
  15. Roman Havlicek14,
  16. Martin Kovar15,
  17. Petr Sevcik16,
  18. Vladimir Rohan16,
  19. Jan Fiksa17,
  20. Bijoy K Menon18,
  21. Robert Mikulik1,2
  1. 1 Department of Neurology, St Anne’s University Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic
  2. 2 International Clinical Research Centre, Stroke Research Program, St Anne’s University Hospital, Brno, Czech Republic
  3. 3 Department of Radiology, Charles University, Faculty of Medicine and University Hospital, Hradec Kralove, Czech Republic
  4. 4 Department of Neurology, University Hospital Ostrava, Faculty of Medicine, University Ostrava, Ostrava, Czech Republic
  5. 5 Department of Medical Imaging, St Anne’s University Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic
  6. 6 Department of Neurology, Charles University, Faculty of Medicine and University Hospital, Hradec Kralove, Czech Republic
  7. 7 Department of Neurology, Palacky University Medical School, Olomouc, Czech Republic
  8. 8 Department of Neurology, Charles University, 2nd Medical Faculty, Prague, Czech Republic
  9. 9 Department of Radiology, University Hospital and Palacky, University Medical School, Olomouc, Czech Republic
  10. 10 Department of Radiology, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Usti nad Labem, Czech Republic
  11. 11 Department of Radiology, Masaryk Hospital, Usti nad Labem, Czech Republic
  12. 12 Department of Neurology, Hospital Ceske Budejovice, Statutory City, Czech Republic
  13. 13 Neurocentre, Regional Hospital Liberec, Liberec, Czech Republic
  14. 14 Department of Neurology, Military University Hospital, Prague, Canada
  15. 15 Department of Neurology, Na Homolce Hospital, Prague, Czech Republic
  16. 16 Department of Neurology, Faculty of Medicine in Pilsen, Charles University in Prague, Pilsen, Czech Republic
  17. 17 Department of Neurology, Charles University, First Faculty of Medicine and General University Hospital, Prague, Czech Republic
  18. 18 Departments of Clinical Neurosciences, Radiology, and Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Canada
  1. Correspondence to Dr Ondrej Volny, Department of Neurology, St. Anne’s University Hospital and Faculty of Medicine, Masaryk University, 53 Pekarska, 602 00 Brno, Czech Republic; 214565{at}mail.muni.cz

Abstract

Background Randomized clinical trials have proven mechanical thrombectomy (MT) to be a highly effective and safe treatment in acute stroke. The purpose of this study was to compare neurothrombectomy data from the Czech Republic (CR) with data from the HERMES meta-analysis.

Methods Available nationwide data for the CR from 2016 from the Safe Implementation of Treatments in Stroke–Thrombectomy (SITS-TBY) registry for patients with terminal internal carotid artery (ICA) and/or middle cerebral artery (MCA) occlusions were compared with data from HERMES. CR and HERMES patients were comparable in age, sex, and baseline National Institutes of Health Stroke Scale scores.

Results From a total of 1053 MTs performed in the CR, 845 (80%) were reported in the SITS-TBY. From these, 604 (72%) were included in this study. Occlusion locations were as follows (CR vs HERMES): ICA 22% versus 21% (P=0.16), M1 MCA 62% versus 69% (P=0.004), and M2 MCA 16% versus 8% (P<0.0001). Intravenous thrombolysis was given to 76% versus 83% of patients, respectively (P=0.003). Median onset to reperfusion times were comparable: 232 versus 285 min, respectively (P=0.66). A modified Thrombolysis in Cerebral Infarction score of 2b/3 was achieved in 74% (433/584) versus 71% (390/549) of patients, respectively (OR 1.17, 95% CI 0.90–1.5, P=0.24). There was no statistically significant difference in the percentage of parenchymalhematoma type 2 (OR 1.12, 95% CI 0.66–1.90, P=0.68). A modified Rankin Scale score of 0–2 at 3 months was achieved in 48% (184/268) versus 46% (291/633) of patients, respectively (OR 0.92, 95% CI 0.71–1.18, P=0.48).

Conclusions Data on efficacy, safety, and logistics of MT from the CR were similar to data from the HERMES collaboration.

  • stroke
  • thrombectomy

https://doi.org/10.1136/neurintsurg-2017-013534

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    Introduction

    Recent randomized trials have demonstrated that mechanical thrombectomy (MT) with second generation neurothrombectomy devices represents a highly effective and safe treatment for patients with acute ischemic stroke due to occlusion(s) in the anterior cerebral circulation.1–5 Data from the HERMES meta-analysis have proven the degree of benefit of this procedure to be substantial; for every 100 patients treated, 38 will have a less disabled outcome than those who receive the best possible medical treatment (intravenous thrombolysis (IV tPA)), and 20 more will achieve functional independence (defined as a modified Rankin Scale score of <2).6

    Nevertheless, several limitations have emerged concerning the methodological background of the HERMES trial, including the fact that all of the data from this study came from high volume comprehensive stroke centers with the highest expertise in endovascular treatment of acute ischemic stroke in the world.

    In order to confirm the broad applicability of MT into real world clinical practice and to establish the treatment effect of MT at a national level, we compared the available neurothrombectomy data from the Czech Republic (CR), prospectively collected in the Safe Implementation of Treatments in Stroke–Thrombectomy (SITS-TBY) registry, with data from the HERMES meta-analysis.

    We hypothesized that the safety and effectiveness of MT in real world clinical practice at a nationwide level were comparable with the results of the randomized controlled trials.

    Methods

    Nationwide data from the CR for the year 2016 were collected from the Safe Implementation of Treatments in Stroke–Thrombectomy (SITS-TBY) registry. SITS is a non-profit, free to use, research driven, independent, international collaboration founded in the Karolinska Institute, Sweden. SITS was set up as an initiative to provide safe implementation of stroke treatments in routine clinical practice. It offers a platform for collecting high quality stroke data in over 1600 stroke centers. The registry is internet based, which allows rapid data entry and retrieval, and allows centers to compare their own treatment results on both a national and global scale.

    Data concerning patients with pretreatment modified Rankin Scale (mRS) scores of <2 and occlusions in the terminal internal carotid artery (ICA) and/or the middle cerebral artery (MCA) treated with second generation neurothrombectomy devices, with or without IV tPA (if eligible), were compared with data from the HERMES meta-analysis.

    Demographic details, vascular risk factors, and National Institutes of Health Stroke Scale (NIHSS) scores (range 0–42, with higher scores indicating severe stroke) were collected for each patient. There was no upper age limit. All patients underwent non-contrast cranial CT followed by CT angiography (CTA) from the aortic arch to the vertex to document large vessel occlusions. Treatment decisions were made in comprehensive stroke centers in accordance with the current European guidelines.7

    Outcomes included: NIHSS score at 24 hours after stroke onset, median change in NIHSS score from baseline to 24 hours, parenchymal hematoma type 2 according to SITS-MOST criteria and achievement of a mRS score of 0–2 at 90 days after stroke onset. Technical efficacy was assessed by counting the number of cases where a modified Thrombolysis in Cerebral Infarction (mTICI) scale score of 2b or 3 was achieved (corresponding to reperfusion of at least 50% of the affected vascular territory). Reported times included: onset to reperfusion time, onset to groin time, and groin to reperfusion time.

    Ethics approval was obtained from the local institutional review boards and written informed consent was obtained from all patients.

    Statistical analysis

    Categorical variables are presented as absolute values and percentages, and continuous variables as mean (SD) if symmetrically distributed, or otherwise as median (IQR).

    We used the Mann–Whitney test to compare continuous and ordinal variables because we did not have access to the raw HERMES data. We used the χ2 test to compare categorical variables. In order to determine whether it was possible to use the above mentioned tests and that the effects were not due to chance alone, we first calculated the intra-cluster correlation coefficient (ICC) for data from each center using Proc Mixed.

    All the tests were two sided and significance was defined as a P value of 0.05. Statistical analyses were obtained using SAS 9.3 software (SAS Institute, Cary, North Carolina, USA).

    Results

    Fourteen of the 15 comprehensive stroke centers in the CR in 2016 reported data to the SITS-TBY registry. In this year, 1053 MTs were performed in the CR. The smallest number of procedures performed by one center was 17 and the largest was 136. Three centers performed more than 100 procedures, six centers performed 50–100 procedures, and six performed <50 procedures per year (17, 34, 34, 34, 43, and 46).8 A total of 845 patients were reported to the registry. Incompleteness of the data and/or patients who did not meet the inclusion criteria led to exclusion of 241 patients. Therefore, the final dataset consisted of 604 (72%) patients, representing 57% of all neurothrombectomy cases performed in 2016 in the CR (with a pretreatment mRS score of <2 and occlusion of the terminal ICA and/or MCA treated with second generation neurothrombectomy devices with or without IV tPA). Seventy per cent of these neurothrombectomies were mothership procedures and 30% were drip and ship procedures.

    CR and HERMES patients were comparable in age, sex, and baseline NIHSS. More CR patients were hypertensive and had diabetes mellitus, and fewer patients were smokers. Fewer patients in the SITS-TBY cohort were treated with IV tPA: 76% versus 83% (P=0.003). Occlusion locations were as follows (CR vs HERMES): terminal ICA 22% versus 21% (P=0.16), M1 MCA 62% versus 69% (P=0.004), and M2 MCA 16% versus 8% (P<0.0001). The median time from onset to reperfusion were comparable: 232 versus 285 min, respectively (P=0.66). The median times from groin to reperfusion time were 58 versus 63 min, respectively. Czech SITS-TBY and HERMES data are summarized in  Table 1.

    View this table:
    Table 1

    Comparison of Czech SITS-TBY and HERMES data available for demographic characteristics, past medical history, clinical and radiological characteristics, treatment details, and outcomes

    Modified TICI 2b/3 was achieved in 74% (433/584) versus 71% (390/549) of patients, respectively (CR vs HERMES; OR 1.17 (95% CI 0.90 to 1.51), P=0.24). CR and HERMES patients did not differ in median change in NIHSS score from baseline to 24 hours. There was no difference in percentage of parenchymal hematoma type 2  (5.7 vs 5.1%; OR 1.12 (95% CI 0.66 to 1.90), P=0.68). An mRS score of 0–2 at 3 months was achieved in 48% (184/268) versus 46% (291/633) of patients (OR 0.92 (95% CI 0.71 to 1.18), P=0.48) (figure 1).

    Figure 1
    Figure 1

    Modified Rankin Scale (mRS) scores at 90 days. Distribution of scores at 90 days in the HERMES (n=634) and Czech SITS-TBY (n=268) groups.

    The ICC for the mRS scores was estimated to be 0.023 and the ICC for NIHSS at 24 hours was 0.058, indicating only negligible differences among the center.

    Discussion

    Our analysis of the available national data on MT from the SITS-TBY registry confirms the applicability of neurothrombectomy in real world clinical practice.

    As two-thirds of the patients from the SITS-TBY registry had complete data, our analysis provides a relatively accurate population based snapshot of the efficacy of MT, comparable with the randomized control trials and previously published real world thrombectomy experiences. STRATIS, the largest prospective multicenter (55 US centers) non-randomized registry, including patients undergoing MT with the Solitaire device, demonstrated that this procedure can be safely and efficaciously performed in the community setting.9 Before the revelation of the STRATIS results, published data concerning MT were limited, arising from mostly single center studies with relatively low numbers of patients.10 11 One of the strengths of our study is that we included nationwide patient data from 14 comprehensive stroke centers from the year 2016 (thus after the publication of the randomized controlled trials).

    A total of 1053 MTs with second generation neurothrombectomy devices were performed in the CR in 2016. If we take into the account the estimated incidence of acute ischemic stroke in the CR (211 per 1 00 000 inhabitants according to a recent stroke epidemiology survey), then approximately 5% of all acute ischemic stroke patients were treated with MT in 2016.12 This relatively high proportion of thrombectomy patients is consistent with previously reported data on MT eligibility, reflecting the high level of organization of acute stroke care in the CR.13–15

    The Institute for Health Information and Statistics of the Czech Republic has been collecting medical information for all patients admitted to all hospitals since 1992. All medical facilities are required by law to register all admissions and discharges, and according to the Guidelines of the Czech Stroke Society, every patient with a diagnosis of stroke should be hospitalized and receive appropriate care in a specialized stroke unit. Since September 2016, the Czech Stroke Society have been monitoring MTs performed in the CR. Every 3 months they report data on the number of MTs performed per month and per center, the percentage of door to needle times <30 min in IV tPA eligible patients, and procedural times, including median onset to groin time, median door to groin time, and median groin to reperfusion. Summary data reports, including the parameters mentioned above, are sent to all stroke centers and physicians involved in stroke care (neurologists and interventional radiologists). This serves as an important tool for improving acute stroke care logistics and reducing procedural times.

    A brief overview of acute stroke care management in the CR is outlined below (CR population in 2016 was 10.56 million; area: 78 866 km2).

    1. Stroke medicine is recognized as a subspecialty of neurology by the Czech Ministry of Health. A dense stroke unit network exists in the CR. There are 47 national stroke centers in the CR, including 15 neurothrombectomy/comprehensive stroke centers with a catchment area of 7 00 000 to 8 00 000 inhabitants. There are no private stroke centers.

    2. The vast majority of neurothrombectomy operators in the CR are interventional radiologists (endovascular stroke therapy is provided by angiologists in one center). Currently, there is an ongoing process by the Czech Society of Interventional Radiology to certify interventional radiologists for endovascular stroke therapy, which is supposed to be completed in 2018. Since a board certification in interventional radiology is included in the criteria, there is only one angiologist who fulfills it. In 2016, 49 physicians were trained in neurothrombectomy (1–5 per center). The total number of interventionalists in all 15 national comprehensive stroke centers was 64 (2–6 per center).

    3. Guidelines and regulatory documents issued by the Czech Ministry of Health require that every patient suspected to have acute stroke must be transported to a hospital with a stroke unit.

    4. There is only one emergency medical service in the CR. It complies with the regulations by the Czech Ministry of Health.

    5. All patients with suspected stroke must have a consultation with a stroke physician in a regional comprehensive stroke center. If there is a suspicion of a large vessel occlusion, then the patient is directly transported to the neurothrombectomy center (after a telephone consultation); otherwise he/she is transported to the nearest stroke center where CT and CTA are performed and IV tPA might be initiated. If the patient transported to stroke center is a candidate for MT, then the neurothrombectomy center is contacted and the patient is transported secondarily to this center.

    6. By law, all hospitals are required to report every hospitalization to the national registry. Reporting to the SITS-TBY registry is voluntary but recommended.

    Randomized trials have demonstrated that workflow speeds are strongly associated with better functional outcomes, thus the reduction of procedural times should be targeted in everyday clinical practice.16–18 Available onset to reperfusion and onset to groin times in our analysis (467 and 426 patients, respectively) are consistent with the HERMES meta-analysis, suggesting good prehospital and inhospital management of neurothrombectomy candidates across the CR.

    A robust predictor of functional outcome is successful reperfusion, defined as achievement of an mTICI score of 2b or 3. Among the 549 HERMES patients who underwent MT intervention and had mTICI scores documented, substantial reperfusion was achieved in 390 (71%) patients, which is consistent with our data (433 of 584 patients had mTICI scores of 2b or 3 (74%)). In terms of the effect on improvement of neurological status, the median change in NIHSS from baseline to 24 hours achieved in the Czech cohort was similar to the HERMES meta-analysis, indicating a comparable clinical effect even in the non-randomized registry. In terms of safety, the proportion of patients with symptomatic parenchymal hemorrhage type 2 was also similar (5.7 vs 5.1%). The mRS scores at 3 months as a marker of long term disability were available in only 60% of our patients. The proportion of available patients with a good clinical outcome (mRS scores of 0–2) was comparable (48 vs 46%). Nevertheless, it is important to be aware of the proportion of missing long term outcome data. On the other hand, comparable short term outcomes mentioned above (NIHSS scores at 24 hours and median change in NIHSS from baseline to 24 hours) indicate a positive effect of the procedure on early clinical outcome.

    Although cerebral and vascular imaging is done in all IV tPA and MT eligible patients in the CR before treatment decision making, Alberta Stroke Program Early CT (ASPECT) scores were not available in the SITS-TBY registry.8 There are only two randomized controlled trials on MT in acute stroke published in which baseline cerebral imaging data were not used to select patients on the basis of the size of ischemic territory, as determined by ASPECTS (THRACE and MR CLEAN).1 19 According to the current European guidelines and the results of our questionnaire survey in January 2017, we can estimate that the majority of patients treated with MT in the CR in 2016 had ASPECT scores <5 and were treated within 8 hours from stroke onset.7 8

    From a demographic standpoint, HERMES and the Czech SITS-TBY cohorts were balanced for age, sex, and history of atrial fibrillation. The groups differed in the proportions of hypertensive, diabetic, and smoking patients. Patients were comparable in the severity of admission neurological deficit assessed by NIHSS (moderate to severe stroke). HERMES and Czech SITS-TBY populations differed in clot locations in the M1 and M2 segments of the MCA, as assessed by local radiologists and referred to in the SITS-TBY registry, indicating that more interventions occurred for distal occlusions. Nevertheless, it is important to consider a challenge associated with a relatively poor standardization in distinguishing between the M1 and M2 MCA segments rated by different radiologists in our non-randomized analysis without a core laboratory rating of clot locations. The limitation of M1/M2 misclassification has been discussed in HERMES and elsewhere.6 20

    Our study had several limitations. We are aware that our comparisons with the clinical trials mentioned above are merely qualitative, as our data were based on a retrospective analysis of prospective registry data (SITS-TBY registry). As mTICI scoring was performed by the same attending interventionalist, who performed the procedure, and as clinical evaluation of disability (NIHSS and mRS) was not completely blinded, there may have been a source of bias. Additionally, there are no imaging data stored in the SITS-TBY registry for neuroimaging core laboratory re-assessment, thus the possibility for misclassification of M1/M2 segments of MCA on CTA, as discussed above, or mTICI on final run DSA, exists and limits our analysis. Another limitation is missing long term outcome data in the SITS-TBY registry.

    In conclusion, our analysis confirms the applicability of neurothrombectomy in a nationwide real world practice for a CTA proven large vessel occlusion in the anterior cerebral circulation and use of the second generation neurothrombectomy devices, and that it is a timely treatment.

    Acknowledgments

    The authors thank and are grateful to all who contribute to the SITS-TBY registry. English proofreading was done by Adam Whitley, MD.

    References

    1. ↵
      2. Berkhemer OA ,
      3. Fransen PS ,
      4. Beumer D , et al
      . A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med 2015;372:11–20.doi:10.1056/NEJMoa1411587
      OpenUrlCrossRefPubMedWeb of Science
    2. ↵
      2. Goyal M ,
      3. Demchuk AM ,
      4. Menon BK , et al
      . Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med 2015;372:1019–30.doi:10.1056/NEJMoa1414905
      OpenUrlCrossRefPubMed
    3. ↵
      2. Saver JL ,
      3. Goyal M ,
      4. Bonafe A , et al
      . Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med 2015;372:2285–95.doi:10.1056/NEJMoa1415061
      OpenUrlCrossRefPubMed
    4. ↵
      2. Jovin TG ,
      3. Chamorro A ,
      4. Cobo E , et al
      . Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med 2015;372:2296–306.doi:10.1056/NEJMoa1503780
      OpenUrlCrossRefPubMed
    5. ↵
      2. Campbell BC ,
      3. Mitchell PJ ,
      4. Kleinig TJ , et al
      . Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med 2015;372:1009–18.doi:10.1056/NEJMoa1414792
      OpenUrlCrossRefPubMed
    6. ↵
      2. Goyal M ,
      3. Menon BK ,
      4. 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;387:1723–31.doi:10.1016/S0140-6736(16)00163-X
      OpenUrlCrossRefPubMed
    7. ↵
      2. Wahlgren N ,
      3. Moreira T ,
      4. Michel P , et al
      . Mechanical thrombectomy in acute ischemic stroke: Consensus statement by ESO-Karolinska Stroke Update 2014/2015, supported by ESO, ESMINT, ESNR and EAN. Int J Stroke 2016;11:134–47.doi:10.1177/1747493015609778
      OpenUrlCrossRefPubMed
    8. ↵
      2. Volny O ,
      3. Bar M ,
      4. Krajina A , et al
      . A comprehensive nationwide evaluation of stroke centres in the Czech Republic performing mechanical thrombectomy in acute stroke in 2016. Cesk Slov Neurol N 2017;113:1–6.
      OpenUrl
    9. ↵
      2. Mueller-Kronast NH ,
      3. Zaidat OO ,
      4. Froehler MT , et al
      . Systematic evaluation of patients treated with neurothrombectomy devices for acute ischemic stroke: primary results of the STRATIS registry. Stroke 2017;48 2760 2768.doi:10.1161/STROKEAHA.117.016456
      OpenUrlAbstract/FREE Full Text
    10. ↵
      2. Carvalho A ,
      3. Cunha A ,
      4. Rodrigues M , et al
      . Mechanical thrombectomy in acute ischemic stroke: initial single-center experience and comparison with randomized controlled trials. J Stroke Cerebrovasc Dis 2017;26:589–94.doi:10.1016/j.jstrokecerebrovasdis.2016.11.116
      OpenUrlCrossRefPubMed
    11. ↵
      2. Nikoubashman O ,
      3. Jungbluth M ,
      4. Schürmann K , et al
      . Neurothrombectomy in acute ischaemic stroke: a prospective single-centre study and comparison with randomized controlled trials. Eur J Neurol 2016;23:807–16.doi:10.1111/ene.12944
      OpenUrl
    12. ↵
      2. Sedova P ,
      3. Brown RD ,
      4. Zvolsky M , et al
      . Incidence of hospitalized stroke in the Czech Republic: the national registry of hospitalized patients. J Stroke Cerebrovasc Dis 2017;26:979–86.doi:10.1016/j.jstrokecerebrovasdis.2016.11.006
      OpenUrl
    13. ↵
      2. Urra X ,
      3. Abilleira S ,
      4. Dorado L , et al
      . Mechanical thrombectomy in and outside the REVASCAT trial: insights from a concurrent population-based stroke registry. Stroke 2015;46:3437–42.doi:10.1161/STROKEAHA.115.011050
      OpenUrlAbstract/FREE Full Text
    14. ↵
      2. Tsivgoulis G ,
      3. Goyal N ,
      4. Mikulik R , et al
      . Eligibility for mechanical thrombectomy in acute ischemic stroke: A phase IV multi-center screening log registry. J Neurol Sci 2016;371:96–9.doi:10.1016/j.jns.2016.10.018
      OpenUrl
    15. ↵
      2. Chia NH ,
      3. Leyden JM ,
      4. Newbury J , et al
      . Determining the number of ischemic strokes potentially eligible for endovascular thrombectomy: a population-based study. Stroke 2016;47:1377–80.doi:10.1161/STROKEAHA.116.013165
      OpenUrlAbstract/FREE Full Text
    16. ↵
      2. Saver JL ,
      3. Goyal M ,
      4. van der Lugt A , et al
      . Time to treatment with endovascular thrombectomy and outcomes from ischemic stroke: a meta-analysis. JAMA 2016;316:1279–88.doi:10.1001/jama.2016.13647
      OpenUrlCrossRefPubMed
    17. ↵
      2. Sheth SA ,
      3. Jahan R ,
      4. Gralla J , et al
      . Time to endovascular reperfusion and degree of disability in acute stroke. Ann Neurol 2015;78:584–93.doi:10.1002/ana.24474
      OpenUrlCrossRefPubMed
    18. ↵
      2. Ribo M ,
      3. Molina CA ,
      4. Cobo E , et al
      . Association between time to reperfusion and outcome is primarily driven by the time from imaging to reperfusion. Stroke 2016;47:999–1004.doi:10.1161/STROKEAHA.115.011721
      OpenUrlAbstract/FREE Full Text
    19. ↵
      2. Bracard S ,
      3. Ducrocq X ,
      4. Mas JL , et al
      . Mechanical thrombectomy after intravenous alteplase versus alteplase alone after stroke (THRACE): a randomised controlled trial. Lancet Neurol 2016;15:1138–47.doi:10.1016/S1474-4422(16)30177-6
      OpenUrlCrossRefPubMed
    20. ↵
      2. Sarraj A ,
      3. Sangha N ,
      4. Hussain MS , et al
      . Endovascular therapy for acute ischemic stroke with occlusion of the middle cerebral artery M2 segment. JAMA Neurol 2016;73:1291–6.doi:10.1001/jamaneurol.2016.2773
      OpenUrl

    Footnotes

    • Contributors OV, RM, and BKM: substantial contributions to the conception or design of the work; the acquisition, analysis, and interpretation of the data; drafting the work and revising it critically for important intellectual content. SB: analysis and interpretation of the data. AK, MB, PC, RH, DS, AT, MK, MR, RP, FC, MN, LJ, RH, VR, MK, PS, and JF: data acquisition, drafting the work and revising it critically for important intellectual content.

    • Funding This work was supported by National Program of Sustainability II, Czech Republic, grant No LQ1605.

    • Competing interests None declared.

    • Ethics approval The study was approved by the local institutional review boards.

    • Provenance and peer review Not commissioned; externally peer reviewed.