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Real-world setting comparison of bridging therapy versus direct mechanical thrombectomy for acute ischemic stroke: A meta-analysis
Bin Qina,b,c,1, Tao Weia,b,1, Wen Gaoa,b,1, Hui-xun Qina,b, Yu-Ming Lianga,b, Cheng Qina,b, Hong Chena,b, Ming-Xiu Yanga,b,
Corresponding author
lzrmyyymx@126.com

Corresponding author.
a Department of Neurology, Liuzhou People's Hospital, Liuzhou, Guangxi, China
b Liuzhou Key Laboratory of Epilepsy Prevention and Research, Liuzhou, Guangxi, China
c Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0001" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0008">Introduction</span><p id="para0008" class="elsevierStylePara elsevierViewall">Stroke is becoming increasingly significant as a major public health concern&#46; It continues to hold its position as the second highest cause of death globally&#44; and when considering death and disability together&#44; it ranks as the third highest cause worldwide&#46; In terms of the number of cases&#44; the burden of stroke has noticeably risen&#44; as evidenced by the latest Global Burden of Diseases stroke burden estimates for 2019&#46;<a class="elsevierStyleCrossRef" href="#bib0001"><span class="elsevierStyleSup">1</span></a> Approximately 70 &#37; of strokes worldwide occur as ischaemic strokes&#44; and the proportion in the United States is higher&#44; at about 85 &#37;&#8211;87 &#37;&#59; of which&#44; Large-Vessel Occlusion &#40;LVO&#41; accounts for half of them&#46;<a class="elsevierStyleCrossRef" href="#bib0002"><span class="elsevierStyleSup">2</span></a> Patients with Acute Ischaemic Stroke &#40;AIS&#41; caused by LVO usually have bigger infarct sizes&#44; more disabling symptoms&#44; and high mortality rates and poor outcomes&#46;<a class="elsevierStyleCrossRef" href="#bib0003"><span class="elsevierStyleSup">3</span></a> Fortunately&#44; reperfusion therapies have improved the clinical outcomes of many patients with AIS&#44; preventing death and disability&#46; However&#44; the treatment of patients with AIS depends on the time since stroke onset&#44; the severity of neurologic deficit&#44; and the results of neuroimaging&#46; Treatment options for AIS need to be understood in order to ensure prompt treatment and improve clinical outcomes&#46;</p><p id="para0009" class="elsevierStylePara elsevierViewall">Intravenous Thrombolysis &#40;IVT&#41; has been proven to be safe and effective in improving the clinical prognosis of patients with AIS&#46; However&#44; by incorporating its narrow therapeutic time window&#44; there are a number of limitations that prevent its wider development and use&#46;<a class="elsevierStyleCrossRef" href="#bib0004"><span class="elsevierStyleSup">4</span></a> The low rate of early reperfusion among patients with LVO also limits IVT&#39;s efficacy&#46;<a class="elsevierStyleCrossRef" href="#bib0004"><span class="elsevierStyleSup">4</span></a> Thus&#44; for patients with AIS caused by an anterior circulatory LVO&#44; Mechanical Thrombectomy &#40;MT&#41; has become the standard treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">5</span></a> One proposal is that administering IVT before MT &#40;known as Bridging Therapy &#91;BT&#93;&#41; could decrease the duration of successful MT by altering the characteristics of the blood clot&#44; enhancing its responsiveness to mechanical intervention&#44; and eliminating any remaining thrombotic material&#46; This suggestion takes into account the distinctions between IVT and MT regarding procedures&#44; time frame&#44; and canalization mechanism&#46; Therefore&#44; for patients with AIS who are eligible for both IVT and MT&#44; current guidelines recommend BT&#46; However&#44; IVT has inherent unfavorable effects despite its substantial efficacy as a reperfusion strategy&#46; The use of IVT may delay the start of MT and increase the risk of Symptomatic Intracranial Haemorrhage &#40;sICH&#41;&#44; and IVT can also lead to distal migration due to thrombus fragmentation as well as higher procedure costs of procedures&#46;<a class="elsevierStyleCrossRef" href="#bib0006"><span class="elsevierStyleSup">6</span></a> In light of these opposing factors&#44; investigators have questioned whether pre-treatment with IVT is beneficial in the long run&#46;</p><p id="para0010" class="elsevierStylePara elsevierViewall">Over several years&#44; meta-analyses of observational studies comparing BT with direct MT have suggested that BT has a greater benefit&#46;<a class="elsevierStyleCrossRefs" href="#bib0007"><span class="elsevierStyleSup">7-9</span></a> Nevertheless&#44; pooling observational study datasets without properly matching statistical techniques may produce flawed conclusions&#46; On the other hand&#44; several groups have performed Randomised Controlled Trials &#40;RCTs&#41; to examine the efficacy and safety of BT in patients with LVO compared with direct MT&#46; The results of these RCTs and their meta-analyses showed that direct MT had comparable consequences to BT in terms of efficacy and safety outcomes for patients with AIS due to LVO&#46;<a class="elsevierStyleCrossRef" href="#bib0004"><span class="elsevierStyleSup">4</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">10-14</span></a> which was inconsistent with the aforementioned meta-analyses of observational studies&#46; A recent individual participant data meta-analysis of RCTs also did not establish non-inferiority of direct MT compared with BT&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">15</span></a> However&#44; several methodological factors confound the interpretation of the results&#44; including not meeting the pre-specified margins of noninferiority and terminating early&#46; Moreover&#44; it is important to remember that RCTs are limited in their ability to generalize to larger and often more representative populations of patients&#44; healthcare providers&#44; and settings where concomitant disorders&#44; medications&#44; and adherence to treatment may differ significantly&#46;<a class="elsevierStyleCrossRefs" href="#bib0016"><span class="elsevierStyleSup">16-18</span></a> In addition to inappropriate physician decisions&#44; lack of professional equipment&#44; and other factors might also contribute to the reduction of the therapeutic effect of MT in real-world practice&#46;<a class="elsevierStyleCrossRef" href="#bib0019"><span class="elsevierStyleSup">19</span></a> Real-world evidence&#44; such as electronic health records&#44; claims data&#44; and disease registries&#44; complements clinical trial evidence derived from RCTs&#46;<a class="elsevierStyleCrossRef" href="#bib0016"><span class="elsevierStyleSup">16</span></a> More recently&#44; several reports were published comparing the safety and efficacy of BT with direct MT in real-world settings&#44; such as national patient samples&#44; multinational&#44; and nationwide registries&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">20-23</span></a> However&#44; these reports differ significantly in terms of data sources and methods of analysis&#46;</p><p id="para0011" class="elsevierStylePara elsevierViewall">Therefore&#44; the authors performed a meta-analysis of the available real-world evidence from nationwide or health organization registry databases focusing on the efficacy and safety of BT compared with direct MT in patients with AIS due to LVO&#46;</p></span><span id="sec0002" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0009">Methods</span><p id="para0012" class="elsevierStylePara elsevierViewall">The authors followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis &#40;PRISMA&#41; statement guidelines when writing this report&#44; and the study was registered in the PROSPERO database &#40;CRD42023421973&#41;&#46;</p><span id="sec0003" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0010">Patient and public involvement</span><p id="para0013" class="elsevierStylePara elsevierViewall">There was no patient or public involvement&#44; and ethical approval was not required for this study&#46;</p></span><span id="sec0004" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0011">Search strategy and eligibility criteria</span><p id="para0014" class="elsevierStylePara elsevierViewall">The authors searched PubMed&#44; Cochrane Library&#44; Embase&#44; and Web of Science until 01 February 2023 using the terms &#8220;stroke&#8221; AND &#8220;thrombectomy OR endovascular&#8221; AND &#8220;thrombolysis OR alteplase OR bridging therapy&#8221; AND &#8220;real world&#8221; OR &#8220;observational&#8221; OR &#8220;registry&#8221; OR &#8220;cohort&#8221; &#40;Table S1 in the Supplementary File&#41;&#46; The references of previous reviews and included studies of this meta-analysis were manually screened to avoid missing any eligible studies that were not previously identified&#46; The authors included all studies satisfying the following criteria&#58; &#40;1&#41; Observational studies that compared BT with direct MT in adult patients with AIS due to LVO&#44; and to ensure that the highest quality datasets were included&#44; only nationwide or health organization registry databases were eligible&#46;<a class="elsevierStyleCrossRef" href="#bib0016"><span class="elsevierStyleSup">16</span></a> &#40;2&#41; At least one outcome of interest must have been reported in the included studies&#59; and &#40;3&#41; When the included studies used the same data source with overlapping study periods&#44; the authors only included the study with the longest study period unless the study periods did not overlap or unless the study included data from another source&#46; Studies were excluded if they &#40;1&#41; were post hoc analyses of RCTs and &#40;2&#41; were case reports&#44; reviews&#44; or studies with incomplete data&#46;</p></span><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0012">Study selection&#44; data extraction&#44; study outcomes&#44; and assessment of bias</span><p id="para0015" class="elsevierStylePara elsevierViewall">Two investigators &#40;BQ and WG&#41; independently screened the titles and abstracts&#44; and full-text articles were reviewed and evaluated&#46; Any discrepancies or uncertainties were resolved through consensus or discussion with a third investigator &#40;MXY&#41;&#46; Two investigators &#40;BQ and TW&#41; independently extracted the following data using a standardized form&#58; first author&#44; publication date&#44; study location&#44; demographic characteristics&#44; vessel occlusion sites&#44; functional outcomes&#44; sICH&#44; mortality&#44; and other detailed characteristics of the included studies&#46; Disagreements were resolved by consensus or discussion with a third investigator &#40;MXY&#41;&#46;</p><p id="para0016" class="elsevierStylePara elsevierViewall">The primary efficacy outcomes were the proportion of patients who achieved excellent functional outcomes &#40;modified Rankin Scale &#91;mRS&#93; score 0&#8211;1&#41; at 90 days and favorable discharge disposition &#40;to the home with or without services&#41;&#46; Secondary efficacy outcomes were the proportion of patients who achieved favorable functional outcomes &#40;mRS score 0&#8211;2&#41; at 90 days and successful reperfusion on postprocedural angiography &#40;defined as Thrombolysis in Cerebral Infarction score &#8805;2b&#41;&#46; Safety outcomes were based on the rates of sICH and mortality at 90 days&#46; sICH was defined according to the Heidelberg Bleeding Classification&#44; Safe Implementation of Thrombolysis in Stroke-Monitoring Study &#40;SITS-MOST&#41; criteria&#44; European Cooperative Acute Stroke Study II criteria &#40;ECASS-II&#41;&#44; and ECASS-III criteria&#46;</p><p id="para0017" class="elsevierStylePara elsevierViewall">The authors used the Risk of Bias in Non-randomised Studies of Interventions &#40;ROBINS-I&#41; tool&#46;<a class="elsevierStyleCrossRef" href="#bib0024"><span class="elsevierStyleSup">24</span></a> to assess the quality of the studies included&#46; The tool evaluates the specific outcomes of each study in seven domains related to the intervention being studied&#46; The level of bias risk in each domain was classified as low&#44; moderate&#44; serious&#44; critical&#44; or no information&#46; Two investigators &#40;BQ and TW&#41; independently evaluated each eligible study&#44; and any disagreements were resolved through discussion with a third investigator &#40;MXY&#41;&#46;</p></span><span id="sec0006" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0013">Data analysis</span><p id="para0018" class="elsevierStylePara elsevierViewall">Pooled Odds Ratios &#40;ORs&#41; with 95 &#37; Confidence Intervals &#40;CIs&#41; were calculated for each outcome between patients receiving BT and those receiving direct MT using random-effects models&#46; For the primary efficacy and safety outcomes &#40;excellent functional outcome at 90 days&#44; favorable discharge disposition&#44; rates of sICH&#44; and mortality at 90 days&#41;&#44; the authors also calculated the pooled adjusted OR &#40;multiple regression or matching analyses&#41; when reported&#46; The authors used the logarithmic-adjusted OR and the corresponding standard errors to calculate the pooled adjusted OR in a random-effects analysis&#46; Logarithmic ORs were calculated with lnOR&#59; standard errors were calculated using &#40;upper CI &#8211; lower CI&#41;&#47;3&#46;92&#46; The heterogeneity between studies was evaluated using the p-value of the &#967;<span class="elsevierStyleSup">2</span> statistics&#46; The I<span class="elsevierStyleSup">2</span> statistics were used to quantify the heterogeneity between studies&#46; Mild&#44; moderate&#44; and high heterogeneity were identified as I<span class="elsevierStyleSup">2</span> values of around 25 &#37;&#44; 50 &#37;&#44; and 75 &#37; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">25</span></a> In addition&#44; the authors performed a sensitivity analysis by limiting the studies to those on AIS attributable to anterior circulation occlusion for the primary efficacy and safety outcomes&#46; All statistical tests were two-sided&#44; with a significance threshold of <span class="elsevierStyleItalic">p</span> &#8804; 0&#46;05&#46; A funnel plot of the reported effect estimates was used to assess for risk of publication bias&#59; in addition&#44; egger&#39;s regression test was employed to evaluate the presence of publication bias&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">25</span></a> All data were analyzed with Review Manager &#40;RevMan&#41; &#40;version 5&#46;4&#59; the Cochrane Collaboration&#44; 2020&#41;&#46;</p></span></span><span id="sec0007" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0014">Results</span><span id="sec0008" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0015">Study selection and characteristics</span><p id="para0019" class="elsevierStylePara elsevierViewall">A total of 4939 records were searched using electronic databases&#44; of which 1186 were excluded because they were duplicates&#46; After retrieving 51 articles for full-text review&#44; 39 articles were excluded because of inappropriate article types &#40;6 RCTs and 15 systematic reviews and meta-analyses&#41;&#44; no nationwide or health insurance claims databases&#44; and no reported interest outcomes&#46; Twelve studies were eventually included after qualitative and quantitative analysis&#44; containing 86&#44;695 patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">20-23</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRefs" href="#bib0026"><span class="elsevierStyleSup">26-33</span></a> The PRISMA flowchart of the study inclusion process can be seen in <a class="elsevierStyleCrossRef" href="#fig0001">Fig&#46; 1</a>&#46;</p><elsevierMultimedia ident="fig0001"></elsevierMultimedia><p id="para0020" class="elsevierStylePara elsevierViewall">The main characteristics of the studies included in this meta-analysis are summarised in <a class="elsevierStyleCrossRef" href="#tbl0001">Table 1</a>&#46; A total of 41&#44;284 patients &#40;47&#46;6 &#37;&#41; in the BT group and 45&#44;411 patients &#40;52&#46;4 &#37;&#41; in the direct MT group were included in the quantitative analysis&#46; Mean&#47;median age was similar between groups &#40;68&#46;5 years for BT and 69&#46;7 years for direct MT&#41;&#46; Female patients accounted for 50 &#37; of cases&#46; Most studies used alteplase as a thrombolytic agent&#44; except for one study that used alteplase and Tenecteplase&#46; The mean&#47;median baseline NIHSS score ranged from 11 to 18 points and was predominantly 16 to 18 points&#46; A total of 7&#47;12 of the included studies included only patients with anterior circulation AIS&#46;</p><elsevierMultimedia ident="tbl0001"></elsevierMultimedia></span><span id="sec0009" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0016">Risk of bias and publication bias</span><p id="para0021" class="elsevierStylePara elsevierViewall">The risk of bias for each individual study using the ROBINS-I tool and across all studies was an overall variable as seen in Table S2 in the Supplementary File&#46; Most studies had a low-to-moderate risk of bias&#46; Visual inspection of the funnel plots and calculation of the Egger test results should not be reported because no more than 10 studies reported each main outcome&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0017">Primary efficacy outcomes</span><p id="para0022" class="elsevierStylePara elsevierViewall">Excellent functional outcome data were available in seven of the included studies&#46; The BT group had statistically significant higher odds for excellent functional outcome &#40;mRS score 0&#8211;1&#41; at 90 days compared with the direct MT group &#40;OR &#61; 1&#46;48&#44; 95 &#37; CI 1&#46;25&#8211;1&#46;75&#44; <span class="elsevierStyleItalic">p</span> &#60; 0&#46;00001&#59; <a class="elsevierStyleCrossRef" href="#fig0002">Fig&#46; 2</a>A&#41;&#44; with moderate heterogeneity &#40;I<span class="elsevierStyleSup">2</span> &#61; 69 &#37;&#41;&#59; and six included studies provided excellent functional outcome data of the adjusted effect estimates&#46; Similarly&#44; the BT group had statistically significant higher odds for excellent functional outcome of the adjusted effect estimates compared with the direct MT group &#40;OR&#61;1&#46;28&#44; 95 &#37; CI 1&#46;04&#8211;1&#46;57&#44; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;02&#59; Fig&#46; S1A in the Supplementary File&#41;&#46; The BT group also had higher odds for favorable discharge disposition &#40;to the home with or without services&#41; &#40;OR &#61; 1&#46;33&#44; 95 &#37; CI 1&#46;29&#8211;1&#46;38&#44; <span class="elsevierStyleItalic">p</span> &#60; 0&#46;00001&#59; <a class="elsevierStyleCrossRef" href="#fig0002">Fig&#46; 2</a>B&#41;&#44; with no statistically significant heterogeneity &#40;I<span class="elsevierStyleSup">2</span> &#61; 0 &#37;&#41;&#46; The favorable discharge disposition of the adjusted effect estimates with the BT group was also higher than the direct MT group &#40;OR &#61; 1&#46;27&#44; 95 &#37; CI 1&#46;17&#8211;1&#46;38&#44; <span class="elsevierStyleItalic">p</span> &#60; 0&#46;00001&#59; Fig&#46; S1B in the Supplementary File&#41;&#46;</p><elsevierMultimedia ident="fig0002"></elsevierMultimedia></span><span id="sec0011" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0018">Safety outcomes</span><p id="para0023" class="elsevierStylePara elsevierViewall">Mortality at 90 days was available for eight included studies&#46; Mortality at 90 days was lower in the BT group than the direct MT group &#40;OR &#61; 0&#46;62&#44; 95 &#37; CI 0&#46;56&#8211;0&#46;70&#44; <span class="elsevierStyleItalic">p</span> &#60; 0&#46;00001&#59; <a class="elsevierStyleCrossRef" href="#fig0003">Fig&#46; 3</a>A&#41;&#44; with mild heterogeneity &#40;I<span class="elsevierStyleSup">2</span> &#61; 29 &#37;&#41;&#44; and the same result was achieved for the mortality of the adjusted effect estimates &#40;OR &#61; 0&#46;73&#44; 95 &#37; CI 0&#46;65&#8211;0&#46;82&#44; <span class="elsevierStyleItalic">p</span> &#60; 0&#46;00001&#59; Fig&#46; S2A in the Supplementary File&#41;&#46; For rates for sICH&#44; however&#44; the BT group was not significantly different compared with the direct MT group &#40;5&#46;6 &#37; vs&#46; 5&#46;0 &#37;&#59; OR &#61; 1&#46;15&#44; 95 &#37; CI 0&#46;97&#8211;1&#46;37&#44; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;11&#59; <a class="elsevierStyleCrossRef" href="#fig0003">Fig&#46; 3</a>B&#41;&#46; The sICH rates of the adjusted effect estimates indicated a possible higher risk of sICH was achieved for the BT group &#40;OR &#61; 1&#46;20&#44; 95 &#37; CI 1&#46;00&#8211;1&#46;44&#44; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;05&#59; Fig&#46; S2B in the Supplementary File&#41;&#46;</p><elsevierMultimedia ident="fig0003"></elsevierMultimedia></span><span id="sec0012" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0019">Secondary efficacy outcomes</span><p id="para0024" class="elsevierStylePara elsevierViewall">For the favorable functional outcome &#40;mRS score 0&#8211;2&#41; at 90 days&#44; the BT group was superior to the direct MT group &#40;OR &#61; 1&#46;46&#44; 95 &#37; CI 1&#46;29&#8211;1&#46;66&#44; <span class="elsevierStyleItalic">p</span> &#60; 0&#46;00001&#59; <a class="elsevierStyleCrossRef" href="#fig0004">Fig&#46; 4</a>A&#41;&#44; with moderate heterogeneity &#40;I<span class="elsevierStyleSup">2</span> &#61; 58 &#37;&#41;&#46; The BT group also had higher odds of successful reperfusion on post-procedural angiography &#40;Thrombolysis in Cerebral Infarction Score &#8805; 2b&#41; &#40;OR &#61; 1&#46;22&#44; 95 &#37; CI 1&#46;06&#8211;1&#46;40&#44; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;005&#59; <a class="elsevierStyleCrossRef" href="#fig0004">Fig&#46; 4</a>B&#41;&#44; with moderate heterogeneity &#40;I<span class="elsevierStyleSup">2</span> &#61; 72 &#37;&#41;&#46;</p><elsevierMultimedia ident="fig0004"></elsevierMultimedia></span><span id="sec0013" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0020">Sensitivity analysis</span><p id="para0025" class="elsevierStylePara elsevierViewall">The sensitivity analysis&#44; by limiting the studies to those on acute ischaemic stroke attributable to anterior circulation occlusion&#44; yielded similar results to the overall analyses of the primary efficacy and safety outcomes &#40;<a class="elsevierStyleCrossRef" href="#fig0003">Fig&#46; 3</a>A&#8210;D and Table S3 in the Supplementary Files&#41;&#46; Compared with the direct MT group&#44; the BT group had significantly higher odds of excellent functional outcome at 90 days &#40;OR &#61; 1&#46;59&#44; 95 &#37; CI 1&#46;45&#8211;1&#46;75&#44; <span class="elsevierStyleItalic">p</span> &#60; 0&#46;00001&#59; Fig&#46; S3A in the Supplementary File&#41; and favorable discharge disposition &#40;OR &#61; 1&#46;32&#44; 95 &#37; CI 1&#46;27&#8211;1&#46;38&#44; <span class="elsevierStyleItalic">p</span> &#60; 0&#46;00001&#59; Fig&#46; S3B in the Supplementary File&#41;&#44; lower mortality at 90 days &#40;OR &#61; 0&#46;60&#44; 95 &#37; CI 0&#46;53&#8211;0&#46;67&#44; <span class="elsevierStyleItalic">p</span> &#60; 0&#46;00001&#59; Fig&#46; S3C in the Supplementary File&#41;&#44; and no significant difference in the sICH &#40;OR &#61; 1&#46;18&#44; 95 &#37; CI 0&#46;98&#8211;1&#46;41&#44; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;07&#59; Fig&#46; S3D in the Supplementary File&#41;&#46;</p></span></span><span id="sec0014" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0021">Discussion</span><p id="para0026" class="elsevierStylePara elsevierViewall">The present meta-analysis of real-world data showed that&#44; compared with the direct MT group&#44; the BT group had higher odds of achieving excellent functional outcomes at 90 days&#44; favorable discharge disposition&#44; favorable functional outcomes at 90 days&#44; successful reperfusion outcomes&#44; and decreased mortality at 90 days in patients with AIS due to LVO&#46; The BT group did not show a significant increase in the risk of experiencing sICH in the crude analysis&#44; however&#44; a potential higher risk of sICH was observed in the adjusted analysis&#46; In addition&#44; the present findings were similar to those of the sensitivity analysis of patients with AIS due to anterior circulation occlusion&#46;</p><p id="para0027" class="elsevierStylePara elsevierViewall">RCTs have been performed to evaluate the efficacy and safety of BT compared with direct MT in the past years&#46; Two RCTs&#44; DIRECT-MT and DEVT&#44; were conducted on Chinese individuals&#46; They showed that direct MT was non-inferior to BT with regard to the better functional outcome at 90 days&#46;<a class="elsevierStyleCrossRef" href="#bib0034"><span class="elsevierStyleSup">34</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">35</span></a> The SKIP was conducted in Japan&#44; which failed to demonstrate the noninferiority of MT alone compared with combined IVT plus MT with regard to favorable functional outcome&#44; however&#44; the point estimates of treatment effect for MT alone was nominally slightly better&#44; not worse&#44; compared with combined therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0036"><span class="elsevierStyleSup">36</span></a> Conversely&#44; two RCTs in Europe showed neither superiority nor non-inferiority&#46;<a class="elsevierStyleCrossRef" href="#bib0037"><span class="elsevierStyleSup">37</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0038"><span class="elsevierStyleSup">38</span></a> Recently&#44; the DIRECT-SAFE recruited patients from Asian &#40;China and Vietnam&#41; versus non-Asian &#40;Australia and New Zealand&#41; regions and did not show non-inferiority of direct MT compared with BT&#46;<a class="elsevierStyleCrossRef" href="#bib0039"><span class="elsevierStyleSup">39</span></a> There is no consensus to guide clinical practice for the superiority of either approach&#44; as these RCTs produced conflicting results&#46; Hence the nationwide registry-based assessment of real-world outcomes represents a meaningful and topical contribution to the growing body of literature on this topic&#46; The present study included real-world data from multiple large-sample nationwide registry databases that incorporated Asian and non-Asian populations&#44; and it showed that BT was associated with better functional outcomes in patients with AIS due to LVO&#46; Therefore&#44; these findings may provide valuable additional information concerning BT versus direct MT in patients with AIS due to LVO&#46;</p><p id="para0028" class="elsevierStylePara elsevierViewall">Previous meta-analyses of the first three RCTs &#40;DEVT&#44; DIRECT-MT and SKIP&#41; suggested among patients with AIS due to LVO&#44; direct MT was non-inferior to BT&#46;<a class="elsevierStyleCrossRef" href="#bib0013"><span class="elsevierStyleSup">13</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">40</span></a>&#44; and similar findings were observed in the pooled analysis of the first four trials &#40;DEVT&#44; DIRECT-MT&#44; SKIP&#44; and MR CLEAN<span class="elsevierStyleGlyphsbnd"></span>NO IV&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0011"><span class="elsevierStyleSup">11</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0012"><span class="elsevierStyleSup">12</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0014"><span class="elsevierStyleSup">14</span></a> Li et al&#46;&#8217;s meta-analysis also found that direct MT had comparable consequences to BT in efficacy and safety outcomes for patients with AIS due to LVO&#46;<a class="elsevierStyleCrossRef" href="#bib0004"><span class="elsevierStyleSup">4</span></a> Unlike the above studies&#44; the present meta-analysis of real-world data found that BT is more beneficial than direct MT in patients with AIS due to LVO&#44; notably for anterior circulation occlusion&#46; However&#44; the DIRECT-MT and DEVT were performed in a Chinese population&#46; This population has a high prevalence of intracranial large-artery atherosclerotic disease&#44; which is a lower response to IVT than cardioembolic stroke&#46;<a class="elsevierStyleCrossRef" href="#bib0041"><span class="elsevierStyleSup">41</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0042"><span class="elsevierStyleSup">42</span></a> Moreover&#44; the authors of DIRECT-MT and DEVT trials also indicated given the relatively long times from hospital arrival to alteplase initiation in these trials&#44; it remains possible that IV alteplase might still be beneficial in the presence of faster delivery times&#46; The SKIP was conducted in Japan&#44; where a low dose of alteplase was used&#46;<a class="elsevierStyleCrossRef" href="#bib0036"><span class="elsevierStyleSup">36</span></a> These factors could have understated the benefits of alteplase in patients receiving BT&#46; In addition&#44; some RCTs and meta-analyses did not meet the pre-specified noninferiority margins&#44; and it is not impossible that the treatment effect of direct MT may be overestimated&#46; In comparison&#44; this study included real-world data from multiple large-sample nationwide and health insurance claims databases that incorporated Asian and non-Asian populations&#46; In order to provide more comprehensive evidence of efficacy for BT&#44; the authors also assessed the outcomes of routine discharge &#40;to home with or without services&#41;&#46; Furthermore&#44; two recent meta-analyses concerning all 6 RCTs indicate that executing MT without the use of alteplase led to worse disability outcomes at the 90 day mark&#44; however&#44; this difference was not statistically significant&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">10</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0043"><span class="elsevierStyleSup">43</span></a> Utilizing this data&#44; the European Stroke Organization-European Society for Minimally Invasive Neurological Therapy &#40;ESO-ESMINT&#41; recommended&#44; on the basis of moderate-quality evidence&#44; that alteplase continue to be used in eligible patients undergoing MT&#46;<a class="elsevierStyleCrossRef" href="#bib0043"><span class="elsevierStyleSup">43</span></a> A recent individual participant data meta-analysis of RCTs also did not establish non-inferiority of direct MT compared with BT&#44; and differences in clinical outcomes were small between the two groups&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">15</span></a> However&#44; the main limitation of the study is that the settings and inclusion criteria of the RCTs underpinning the meta-analysis inherently introduce selection bias&#46; This means that the results are only applicable to patients who present directly to healthcare centers that have the capability of providing endovascular treatment&#46; The findings of the study may not necessarily apply to patients who initially presented to primary stroke centers&#46;<a class="elsevierStyleCrossRef" href="#bib0044"><span class="elsevierStyleSup">44</span></a>&#46; The present findings from real-world data of multiple large-sample nationwide registries support the ESO-ESMINT recommendations and strengthen their validity&#46;</p><p id="para0029" class="elsevierStylePara elsevierViewall">One meta-analysis of RCTs and observational studies with 36&#44;123 patients suggested IVT&#43;MT has slightly higher rates of survival&#44; successful and complete recanalization&#44; and favorable functional outcomes as compared with direct MT&#44; but the raw data of observational studies were used to analyze instead of adjusted effect size for confounding factors<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">45</span></a> Another meta-analysis including patients with anterior circulation occlusion also showed the odds for functional independence&#44; successful reperfusion&#44; and mortality for combined RCTs and observational studies data favored the use of BT over direct MT&#46;<a class="elsevierStyleCrossRef" href="#bib0046"><span class="elsevierStyleSup">46</span></a> Recently&#44; pooled analysis of 55 eligible studies &#40;9 RCTs and 46 observational studies&#41; showed that BT did improve the prognosis for AIS patients and did not increase the risk of hemorrhagic transformation compared with direct MT&#46;<a class="elsevierStyleCrossRef" href="#bib0047"><span class="elsevierStyleSup">47</span></a> The present findings were consistent with these aforementioned meta-analyses &#40;including RCTs and observational studies&#41;&#46; However&#44; in observational studies&#44; baseline characteristics may vary between groups&#44; consequently affecting the outcomes&#46; To reduce possible imbalances between baseline characteristics&#44; the authors combined the statistically adjusted OR results from multiple regression and multivariate match analyses&#46; To ensure that the highest quality data sets are included&#46;<a class="elsevierStyleCrossRef" href="#bib0016"><span class="elsevierStyleSup">16</span></a> only nationwide or health organization registry databases were eligible in the present study&#46; Additionally&#44; the latest&#44; large-sample&#44; nationwide registries have been included in the present study&#44; such as the one maintained by the American Heart Association and American Stroke Association &#40;16&#44;357 patients&#41;<a class="elsevierStyleCrossRef" href="#bib0033"><span class="elsevierStyleSup">33</span></a> and another by the China Stroke Prevention Project Committee &#40;7674 patients&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0029"><span class="elsevierStyleSup">29</span></a>&#46; As a result&#44; this study incorporated the latest real-world data and benefited from a larger sample size &#40;86&#44;695 patients&#41;&#46; Moreover&#44; discharge-modified Rankin Scale score and non-home discharge disposition are good individual predictors of prognostic benefit for patients with AIS following treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0048"><span class="elsevierStyleSup">48</span></a> In order to provide more comprehensive evidence of efficacy for BT&#44; the authors also assessed the outcomes of routine discharge &#40;to home with or without services&#41;&#46;</p><p id="para0030" class="elsevierStylePara elsevierViewall">Although the rate of sICH was slightly higher in patients who underwent BT than in those who underwent direct MT &#40;5&#46;6 &#37; vs&#46; 4&#46;9 &#37;&#41; in the present study&#44; it was still slightly lower than that of previous observational studies on BT &#40;5&#46;8 &#37; in Lin et al&#46;&#44; 6&#46;4 &#37; in Trifan et al&#46; and 6&#46;6 &#37; in Ghaith et al&#46;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0011"><span class="elsevierStyleSup">11</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0012"><span class="elsevierStyleSup">12</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">45</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0046"><span class="elsevierStyleSup">46</span></a> In addition&#44; the real-world data showed that there was no statistically significant difference between the BT and direct MT groups in the rate of sICH in the crude analysis&#46; The present results are consistent with those of previous meta-analyses&#46;<a class="elsevierStyleCrossRef" href="#bib0011"><span class="elsevierStyleSup">11</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0012"><span class="elsevierStyleSup">12</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">45</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0046"><span class="elsevierStyleSup">46</span></a> which showed that the sICH levels were comparable between the two groups&#46; A recent meta-analysis including six recent RCTs also indicated moderate-certainty evidence suggesting that there is possibly a slight increase in sICH with BT compared with direct MT &#40;5&#46;7&#37; vs&#46; 4&#46;3 &#37;&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">10</span></a> but no significant statistical difference between the two groups&#46; Taken together&#44; a slightly increased risk of sICH in patients undergoing BT was observed compared with direct MT in the present study&#44; but no significant statistical difference was observed between the two groups&#46; These findings are consistent with those of previous meta-analyses&#46; Furthermore&#44; there was no significant difference in the incidence of sICH between the two groups when the authors limited the analysis to patients with AIS due to anterior circulation occlusion&#46; Some studies have shown that IVT may increase the risk of intracranial hemorrhage&#46;<a class="elsevierStyleCrossRef" href="#bib0049"><span class="elsevierStyleSup">49</span></a> and sICH is associated with poor 90-day functional independence and higher mortality rates&#46; However&#44; these findings indicated that BT had significantly higher odds for functional outcomes at 90 days and discharge disposition outcomes&#44; and it decreased the risk of mortality at 90 days&#44; despite a slightly increased risk of sICH in patients who underwent BT&#46;</p><p id="para0031" class="elsevierStylePara elsevierViewall">The present study has some limitations&#46; First&#44; although the present meta-analysis had a large sample size and data were derived from nationwide or health insurance claims databases&#44; it also reported an adjusted effect size for confounding factors&#46; However&#44; it is limited by potential unmeasured residual confounding factors&#44; such as selective bias&#44; lack of information about patient characteristics&#44; and varied MT strategies&#44; which may explain the heterogeneity identified for several outcomes and potentially influence the reported results&#46; Second&#44; door-to-groin puncture time was not assessed in this meta-analysis owing to the lack of relevant information in most studies&#46; Nevertheless&#44; when the authors have direct evidence to inform patients of important outcomes&#44; surrogate outcomes &#40;for example&#44; door-groin puncture time&#44; successful reperfusion&#44; and any intracranial hemorrhage&#41; are less important&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">10</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">50</span></a> In addition&#44; the authors could not conduct the subgroup analysis of geographical region &#40;Asian vs&#46; non-Asian regions&#41; because of only two studies recruited patients from the Asian region and provided functional outcomes&#46; Thus&#44; this topic should be explored by more future trials&#46; Third&#44; various criteria were used to define sICH in eligible studies&#44; which might potentially influence the reported results&#46; However&#44; the lack of statistical heterogeneity in the pooled estimates of sICH suggests that these results are valid&#46; Finally&#44; alteplase was primarily used as a thrombolytic agent in the included studies&#46; Therefore&#44; Tenecteplase may be an effective thrombolytic agent&#46; In such cases&#44; additional studies are necessary to determine whether Tenecteplase and MT are more effective than direct MT alone&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0022">Conclusion</span><p id="para0032" class="elsevierStylePara elsevierViewall">The present meta-analysis of real-world data indicated that in patients with AIS due to LVO&#44; BT was associated with better excellent and favorable functional outcomes at 90 days&#44; favorable discharge disposition&#44; successful reperfusion&#44; and mortality at 90 days&#44; without significantly increasing the risk of sICH&#46; These findings support the current practice in a real-world setting and hence strengthen their validity&#46; For patients with AIS due to LVO who are eligible for both IVT and MT&#44; BT will remain the standard treatment until more data are available&#46;</p></span><span id="sec0016" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0023">Funding</span><p id="para0033" class="elsevierStylePara elsevierViewall">This research did not receive any specific grant from funding agencies in the public&#44; commercial&#44; or not-for-profit sectors&#46;</p></span><span id="sec0016a" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0023a">CRediT authorship contribution statement</span><p id="para0033a" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Bin Qin&#58;</span> Conceptualization&#44; Investigation&#44; Formal analysis&#44; Methodology&#44; Writing &#8211; original draft&#46; <span class="elsevierStyleBold">Tao Wei&#58;</span> Investigation&#44; Formal analysis&#44; Methodology&#44; Writing &#8211; review &#38; editing&#46; <span class="elsevierStyleBold">Wen Gao&#58;</span> Investigation&#44; Formal analysis&#44; Methodology&#44; Writing &#8211; review &#38; editing&#46; <span class="elsevierStyleBold">Hui-xun Qin&#58;</span> Resources&#44; Writing &#8211; review &#38; editing&#46; <span class="elsevierStyleBold">Yu-Ming Liang&#58;</span> Writing &#8211; review &#38; editing&#46; <span class="elsevierStyleBold">Cheng Qin&#58;</span> Writing &#8211; review &#38; editing&#46; <span class="elsevierStyleBold">Hong Chen&#58;</span> Writing &#8211; review &#38; editing&#46; <span class="elsevierStyleBold">Ming-Xiu Yang&#58;</span> Conceptualization&#44; Writing &#8211; review &#38; editing&#44; Supervision&#46;</p></span></span>"
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            1 => array:2 [
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              "titulo" => "Search strategy and eligibility criteria"
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              "titulo" => "Study selection&#44; data extraction&#44; study outcomes&#44; and assessment of bias"
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    "pdfFichero" => "main.pdf"
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    "fechaRecibido" => "2023-10-15"
    "fechaAceptado" => "2024-05-13"
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            0 => "Acute ischaemic stroke"
            1 => "Large-vessel occlusion"
            2 => "Intravenous thrombolysis"
            3 => "Bridging therapy"
            4 => "Real-world evidence"
            5 => "Meta-analysis"
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    "highlights" => array:2 [
      "titulo" => "Highlights"
      "resumen" => "<span id="abss0001" class="elsevierStyleSection elsevierViewall"><p id="spara006" class="elsevierStyleSimplePara elsevierViewall"><ul class="elsevierStyleList" id="celist0001"><li class="elsevierStyleListItem" id="celistitem0001"><span class="elsevierStyleLabel">&#8226;</span><p id="para0001" class="elsevierStylePara elsevierViewall">Acute ischaemic stroke is becoming a major public health concern&#46;</p></li><li class="elsevierStyleListItem" id="celistitem0002"><span class="elsevierStyleLabel">&#8226;</span><p id="para0002" class="elsevierStylePara elsevierViewall">The nationwide or health organization registry databases were included&#46;</p></li><li class="elsevierStyleListItem" id="celistitem0003"><span class="elsevierStyleLabel">&#8226;</span><p id="para0003" class="elsevierStylePara elsevierViewall">Bridging therapy remains the standard treatment until more data are available&#46;</p></li></ul></p></span>"
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    "resumen" => array:1 [
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        "resumen" => "<span id="abss0002" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0003">Background and purpose</span><p id="spara007" class="elsevierStyleSimplePara elsevierViewall">Intravenous Thrombolysis &#40;IVT&#41; prior to Mechanical Thrombectomy &#40;MT&#41; for Acute Ischaemic Stroke &#40;AIS&#41; due to Large-Vessel Occlusion &#40;LVO&#41; remains controversial&#46; Therefore&#44; the authors performed a meta-analysis of the available real-world evidence focusing on the efficacy and safety of Bridging Therapy &#40;BT&#41; compared with direct MT in patients with AIS due to LVO&#46;</p></span> <span id="abss0003" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0004">Methods</span><p id="spara008" class="elsevierStyleSimplePara elsevierViewall">Four databases were searched until 01 February 2023&#46; Retrospective and prospective studies from nationwide or health organization registry databases that compared the clinical outcomes of BT and direct MT were included&#46; Odds Ratios &#40;ORs&#41; and 95 &#37; Confidence Intervals &#40;CIs&#41; for efficacy and safety outcomes were pooled using a random-effects model&#46;</p></span> <span id="abss0004" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0005">Results</span><p id="spara009" class="elsevierStyleSimplePara elsevierViewall">Of the 12 studies&#44; 86&#44;695 patients were included&#46; In patients with AIS due to LVO&#44; BT group was associated with higher odds of achieving excellent functional outcome &#40;modified Rankin Scale score 0&#8211;1&#41; at 90 days &#40;OR &#61; 1&#46;48&#44; 95 &#37; CI 1&#46;25&#8211;1&#46;75&#41;&#44; favorable discharge disposition &#40;to the home with or without services&#41; &#40;OR &#61; 1&#46;33&#44; 95 &#37; CI 1&#46;29&#8211;1&#46;38&#41;&#44; and decreased mortality at 90 days &#40;OR &#61; 0&#46;62&#44; 95 &#37; CI 0&#46;56&#8211;0&#46;70&#41;&#44; as compared with the direct MT group&#46; In addition&#44; the risk of symptomatic intracranial hemorrhage did not increase significantly in the BT group&#46;</p></span> <span id="abss0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0006">Conclusion</span><p id="spara010" class="elsevierStyleSimplePara elsevierViewall">The present meta-analysis indicates that BT was associated with favorable outcomes in patients with AIS due to LVO&#46; These findings support the current practice in a real-world setting and strengthen their validity&#46; For patients eligible for both IVT and MT&#44; BT remains the standard treatment until more data are available&#46;</p></span>"
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                  <table border="0" frame="\n
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                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><a name="en0001"></a><th class="td-with-role" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t ; entry_with_role_rowgroup " rowspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Author and year</th><a name="en0002"></a><th class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowgroup " rowspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Study duration</th><a name="en0003"></a><th class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowgroup " rowspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Countries</th><a name="en0004"></a><th class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowgroup " rowspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Data source</th><a name="en0005"></a><th class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowgroup " rowspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Study design</th><a name="en0006"></a><th class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowgroup " rowspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Occluded Vessel</th><a name="en0007"></a><th class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_colgroup " colspan="5" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">BT</th><a name="en0008"></a><th class="td-with-role" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t ; entry_with_role_colgroup " colspan="4" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Direct MT</th></tr><tr title="table-row"><a name="en0015"></a><th class="td" title="\n
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                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">N&#176; of patients&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\t\t</th><a name="en0017"></a><th class="td" title="\n
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                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Female&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0018"></a><th class="td" title="\n
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                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">NIHSS at Admission<a class="elsevierStyleCrossRef" href="#tb1fn1"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">IVT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0020"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">N&#176; of patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0021"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Age &#40;year&#41;<a class="elsevierStyleCrossRef" href="#tb1fn1"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0022"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Female&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0023"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">NIHSS at admission<a class="elsevierStyleCrossRef" href="#tb1fn1"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><a name="en0024"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Ahmed 2021&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0025"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2014 to 2019&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0026"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">European Union&#44; Norway and Iceland&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0027"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Safe Implementation of Treatment in Stroke&#8211;International Stroke Thrombectomy Register&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0028"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">P&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0029"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">AC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0030"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">3944&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0031"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">72 &#40;62&#8211;80&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0032"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">49&#46;9 &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0033"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">16 &#40;11&#8211;20&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0034"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Alteplase&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0035"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2406&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0036"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">74 &#40;64&#8211;81&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0037"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">48&#46;9 &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0038"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">16 &#40;11&#8211;20&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0039"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Casetta 2019&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0040"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2011 to 2015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0041"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Italy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0042"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">The Italian Registry of Endovascular Stroke Treatments&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0043"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">P&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0044"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">AC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0045"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">635&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0046"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">67&#46;6 &#40;14&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0047"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">50&#46;7 &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0048"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">18 &#40;14&#8211;21&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0049"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Alteplase &#40;0&#46;9 mg&#47;kg body weight&#44; maximum 90 mg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0050"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">513&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0051"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">68&#46;8 &#40;13&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0052"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">51&#46;1 &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0053"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">18 &#40;14&#8211;22&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0054"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Chalos 2019&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0055"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2014 to 2016&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0056"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Netherlands&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0057"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Multicenter Randomised Controlled Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands Registry&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0058"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">P&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0059"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">AC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0060"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1161&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0061"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">70 &#40;59&#8211;79&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0062"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">46&#46;0 &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0063"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">16 &#40;11&#8211;20&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0064"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Alteplase &#40;0&#46;9 mg&#47;kg body weight&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0065"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">324&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0066"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">72 &#40;63&#8211;80&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0067"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">47&#46;0 &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0068"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">17 &#40;13&#8211;20&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0069"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Di Maria 2018&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0070"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2012 to 2016&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0071"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">France&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0072"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Endovascular Treatment in Ischemic Stroke registry&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0073"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">P&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0074"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">AC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0075"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">976&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0076"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">67&#46;2 &#40;15&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0077"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">45&#46;7 &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0078"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">17 &#40;11&#8211;20&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0079"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0080"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">531&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0081"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">67&#46;6 &#40;15&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0082"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">48&#46;8 &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0083"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">16 &#40;11&#8211;21&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0084"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Dicpinigaitis 2022&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0085"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2015 to 2018&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0086"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">United States&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0087"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">The National Inpatient Sample &#40;inpatient care databases in the United States&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0088"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">R&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0089"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">AC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0090"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">19&#44;735&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0091"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">68&#46;9 &#40;0&#46;2&#41;<a class="elsevierStyleCrossRef" href="#tb1fn2"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0092"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">50&#46;9 &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0093"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0094"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Alteplase&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0095"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">28&#44;790&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0096"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">69&#46;7 &#40;0&#46;2&#41;<a class="elsevierStyleCrossRef" href="#tb1fn2"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0097"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">53&#46;0 &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0098"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0099"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Geng 2021&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0100"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2018 to 2019&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0101"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">China&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0102"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">China Stroke Prevention Project Committee&#8211; Direct Endovascular Thrombectomy and Bridging Thrombolysis registry&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0103"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">R&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0104"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0105"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2069&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0106"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">68 &#40;58&#8211;76&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0107"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">40 &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0108"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">16 &#40;12&#8211;20&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0109"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Alteplase&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0110"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">5605&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0111"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">67 &#40;58&#8211;75&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0112"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">40 &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0113"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">16 &#40;12&#8211;21&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0114"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Le Floch 2022&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0115"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2015 to 2022&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0116"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">France&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0117"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Endovascular Treatment in Ischemic Stroke registry&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0118"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">R&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0119"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">AC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0120"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">570&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0121"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">69&#46;5 &#40;15&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0122"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">48&#46;6 &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0123"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">11 &#40;7&#8211;17&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0124"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Alteplase or Tenecteplase&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0125"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">562&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0126"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">71&#46;8 &#40;13&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0127"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">50&#46;0 &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0128"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">12 &#40;8&#8211;18&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0129"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Leker 2018&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0130"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2014 to 2016&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0131"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Israel&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0132"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">National Acute Stroke Israeli Survey of Patients Undergoing Revascularization&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0133"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">P&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0134"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">AC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0135"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">159&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0136"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">68&#46;1 &#40;1&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0137"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">43&#46;0 &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0138"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">16&#46;0 &#40;13&#8211;19&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0139"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Alteplase&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0140"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">111&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0141"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">67&#46;4 &#40;15&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0142"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">48&#46;0 &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0143"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">16 &#40;12&#8211;20&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0144"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Minnerup 2016&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0145"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2012 to 2013&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0146"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Germany&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0147"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Register on Revascularization in Ischemic Stroke Patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0148"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">P&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0149"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">AC&#43;PC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0150"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">603&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0151"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">68&#46;3 &#40;13&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0152"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">49&#46;6 &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0153"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">15&#46;1 &#40;6&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0154"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Alteplase&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0155"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">504&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0156"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">68&#46;7 &#40;14&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0157"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">52&#46;0 &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0158"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">14&#46;3 &#40;6&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0159"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Park 2017&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0160"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2008 to 2013&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0161"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Korea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0162"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Clinical Research Center for Stroke-5th division registry&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0163"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">R&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0164"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">AC&#43;PC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0165"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">458&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0166"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">68 &#40;12&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0167"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">43 &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0168"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">15 &#40;11&#8211;19&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0169"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Alteplase &#40;0&#46;6&#47;0&#46;9 mg&#47;kg body weight&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0170"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">181&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0171"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">69 &#40;12&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0172"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">43 &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0173"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">15 &#40;10&#8211;18&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0174"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Smith 2022&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0175"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2019 to 2020&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0176"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">United States&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0177"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Get with the Guidelines-Stroke registry&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0178"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">R&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0179"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">AC&#43;PC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0180"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">10&#44;548&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0181"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">70&#46;0 &#40;59&#46;0&#8211;81&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0182"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">49&#46;1 &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0183"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">16&#46;0 &#40;11&#46;0&#8211;21&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0184"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Alteplase&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0185"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">5284&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0186"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">74&#46;0 &#40;63&#46;0&#8211;83&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0187"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">52&#46;2 &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0188"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">17&#46;0 &#40;11&#46;0&#8211;22&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0189"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Tong 2021&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0190"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2017 to 2019&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0191"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">China&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0192"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Endovascular Treatment Key Technique and Emergency Workflow Improvement of Acute Ischemic Stroke registry&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0193"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">P&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0194"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">AC&#43;PC&nbsp;\t\t\t\t\t\t\n
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Article information
ISSN: 18075932
Original language: English
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