Supplementary materials: MASTRO I: Meta-Analysis and Systematic Review of thrombectomy stent retriever outcomes: comparing functional, safety and recanalization outcomes between EmboTrap, Solitaire and Trevo in acute ischemic stroke

<b>These are peer-reviewed supplementary materials for the article '</b><b>MASTRO I: Meta-Analysis and Systematic </b><b>Review of thrombectomy stent retriever </b><b>outcomes: comparing functional, safety </b><b>and recanalization outcomes between </b><b>EmboTrap, Solitaire and Trevo in acute </b><b>ischemic stroke</b><b>' published in the</b><b> </b><b><i>Journal of Comparative Effectiveness Research</i></b><b>.</b><b>Supplementary Table 1</b><b>:</b><b> </b>Search terms<b>Supplementary Table 2</b><b>:</b><b> </b>Studies excluded for potential population selection bias<b>Supplementary Table 3</b><b>: </b>Study and patient baseline characteristics at the study level<b>Supplementary Table 4</b><b>:</b><b> </b>Combined (EmboTrap, Trevo, and Solitaire) ordinal mRS scores across treatment groups.<b>Supplementary Results 1: </b>Ordinal mRS scores at 90 days<b>Supplementary Results 2: </b>Core-lab subanalysis:<b>Supplementary Results 3: </b>Prospective-only subanalysis.<b>Supplementary Table 5</b><b>:</b><b> </b>Comparison of recanalization outcomes between EmboTrap®, Trevo, and Solitaire among studies with outcomes adjudicated by a core-laboratory.<b>Supplementary Table 6</b><b>:</b><b> </b>Comparisons of functional, safety, and recanalization outcomes between EmboTrap®, Trevo, and Solitaire among prospective studies.<b>Supplementary Figure 1</b><b>:</b><b> </b>Outlier and influence analyses of rates of mRS 0-2 at 90 days<b>Supplementary Figure 2</b><b>:</b><b> </b>Forest plot of comparisons of mRS 0-2 at 90 days.<b>Supplementary Figure 3</b><b>: </b>Forest plot of comparisons of mRS 0-2 at 90 days.<b>Supplementary Figure 4</b><b>:</b><b> </b>Outlier and influence analyses of rates of mortality at 90 days<b>Supplementary Figure 5</b><b>:</b> Forest plot of comparisons of mortality at 90 days.<b>Supplementary Figure 6</b><b>:</b><b> </b>Forest plot of comparisons of mortality at 90 days<b>Supplementary Figure 7</b><b>:</b><b> </b>Outlier and influence analyses of ENT rates<b>Supplementary Figure 8</b><b>:</b> Forest plot of comparisons of ENT/distal emboli.<b>Supplementary Figure 9</b><b>:</b><b> </b>Outlier and influence analyses of sICH rates.<b>Supplementary Figure 10</b><b>:</b><b> </b>Forest plot of comparisons of sICH.<b>Supplementary Figure 11</b><b>:</b><b> </b>Forest plot of comparisons of complete or near-complete recanalization on first pass (FPR mTICI ≥2c).<b>Supplementary Figure 12</b><b>:</b><b> </b>Forest plot of comparisons of successful recanalization on first pass (mFPR mTICI ≥2b).<b>Supplementary Figure 13</b><b>:</b><b> </b>Forest plot of comparisons of final complete recanalization (TICI 3).<b>Supplementary Figure 14</b><b>:</b><b> </b>Forest plot of comparisons of final successful recanalization (mTICI ≥2b).<b>Supplementary Figure 15</b><b>:</b><b> </b>Forest plot of comparisons of complete or near-complete recanalization on first pass (FPR mTICI ≥2c) among core-lab adjudicated studies.<b>Supplementary Figure 16</b><b>:</b><b> </b>Forest plot of comparisons of successful recanalization on first pass (mFPR mTICI ≥2b) among core-lab adjudicated studies.<b>Supplementary Figure 17</b><b>:</b><b> </b>Forest plot of comparisons of final complete recanalization (TICI 3) among core-lab adjudicated studies.<b>Supplementary Figure 18</b><b>:</b><b> </b>Forest plot of comparisons of final successful recanalization (mTICI ≥2b) among core-lab adjudicated studies <b>Supplementary Figure 19</b><b>:</b><b> </b>Forest plot of comparisons of successful recanalization on first pass (mFPR mTICI ≥2b) among prospective studies.<b>Supplementary Figure 20</b><b>: </b>Forest plot of comparisons of final complete recanalization (TICI 3) among prospective studies.<b>Supplementary Figure 21</b><b>:</b><b> </b>Forest plot of comparisons of final successful recanalization (mTICI ≥2b) among prospective studies.<b>Supplementary Figure 22</b><b>:</b><b> </b>Forest plot of comparisons of ENT/distal emboli among prospective studies.<b>Supplementary Figure 23</b><b>:</b><b> </b>Forest plot of comparisons of sICH among prospective studies.<b>Supplementary Figure 24</b><b>:</b><b> </b>Forest plot of comparisons of mRS 0-2 at 90 days among prospective studies.<b>Supplementary Figure 25</b><b>:</b><b> </b>Forest plot of comparisons of mortality at 90 days among prospective studies.<b>Aim: </b>Stent-retriever (SR) thrombectomy has demonstrated superior outcomes in patients with acute ischemic stroke compared with medical management alone, but differences among SRs remain unexplored. We conducted a Systematic Review/Meta-Analysis to compare outcomes between three SRs: EmboTrap , Solitaire™, and Trevo. <b>Methods:</b> We conducted a PRISMA-compliant Systematic Review among English-language studies published after 2014 in PubMed/MEDLINE that reported SRs in ≥25 patients. Functional and safety outcomes included 90-day modified Rankin scale (mRS 0-2), mortality, symptomatic intracranial hemorrhage (sICH), and embolization to new territory (ENT). Recanalization outcomes included modified thrombolysis in cerebral infarction (mTICI) and first-pass recanalization (FPR). We used a random effects Meta-Analysis to compare outcomes; subgroup and outlier-influencer analysis were performed to explore heterogeneity. <b>Results:</b> Fifty-one articles comprising 9,804 patients were included. EmboTrap had statistically significantly higher rates of mRS 0-2 (57.4%) compared with Trevo (50.0%, p = 0.013) and Solitaire (45.3%, p &lt; 0.001). Compared with Solitaire (20.4%), EmboTrap (11.2%, p &lt; 0.001) and Trevo (14.5%, p = 0.018) had statistically significantly lower mortality. Compared with Solitaire (7.7%), EmboTrap (3.9%, p = 0.028) and Trevo (4.6%, p = 0.049) had statistically significantly lower rates of sICH. There were no significant differences in ENT rates across all three devices (6.0% for EmboTrap, 5.3% for Trevo, and 7.7% for Solitaire, p = 0.518). EmboTrap had numerically higher rates of recanalization; however, no statistically significant differences were found. Conclusion: The results of our Systematic Review/Meta-Analysis suggest that EmboTrap may be associated with significantly improved functional outcomes compared with Solitaire and Trevo. EmboTrap and Trevo may be associated with significantly lower rates of sICH and mortality compared with Solitaire. No significant differences in recanalization and ENT rates were found. These conclusions are tempered by limitations of the analysis including variations in thrombectomy techniques in the field, highlighting the need for multi-arm RCT studies comparing different SR devices to confirm our findings.

本文件为发表于《Journal of Comparative Effectiveness Research》（《比较效果研究杂志》）的论文《MASTRO I：血栓取出支架取栓术结局的Meta分析与系统评价：比较EmboTrap、Solitaire与Trevo治疗急性缺血性卒中的功能、安全性及再通结局》的同行评议补充材料。

补充表1：检索词
补充表2：因潜在人群选择偏倚被排除的研究
补充表3：研究层面的研究与患者基线特征
补充表4：各治疗组中EmboTrap、Trevo与Solitaire的改良Rankin量表（modified Rankin Scale, mRS）有序评分
补充结果1：90天改良Rankin量表有序评分
补充结果2：核心实验室亚组分析
补充结果3：仅前瞻性研究亚组分析
补充表5：经核心实验室裁定研究结局的文献中，EmboTrap®、Trevo与Solitaire的再通结局比较
补充表6：前瞻性研究中，EmboTrap®、Trevo与Solitaire的功能、安全性及再通结局比较
补充图1：90天mRS 0-2率的异常值与影响分析
补充图2：90天mRS 0-2比较的森林图
补充图3：90天mRS 0-2比较的森林图
补充图4：90天死亡率的异常值与影响分析
补充图5：90天死亡率比较的森林图
补充图6：90天死亡率比较的森林图
补充图7：新区域栓塞（ENT）率的异常值与影响分析
补充图8：ENT/远端栓塞比较的森林图
补充图9：症状性颅内出血（sICH）率的异常值与影响分析
补充图10：症状性颅内出血（sICH）比较的森林图
补充图11：首次通过完全或近完全再通（FPR mTICI≥2c）比较的森林图
补充图12：首次通过成功再通（mFPR mTICI≥2b）比较的森林图
补充图13：最终完全再通（TICI 3）比较的森林图
补充图14：最终成功再通（mTICI≥2b）比较的森林图
补充图15：经核心实验室裁定的研究中，首次通过完全或近完全再通（FPR mTICI≥2c）比较的森林图
补充图16：经核心实验室裁定的研究中，首次通过成功再通（mFPR mTICI≥2b）比较的森林图
补充图17：经核心实验室裁定的研究中，最终完全再通（TICI 3）比较的森林图
补充图18：经核心实验室裁定的研究中，最终成功再通（mTICI≥2b）比较的森林图
补充图19：前瞻性研究中，首次通过成功再通（mFPR mTICI≥2b）比较的森林图
补充图20：前瞻性研究中，最终完全再通（TICI 3）比较的森林图
补充图21：前瞻性研究中，最终成功再通（mTICI≥2b）比较的森林图
补充图22：前瞻性研究中，ENT/远端栓塞比较的森林图
补充图23：前瞻性研究中，症状性颅内出血（sICH）比较的森林图
补充图24：前瞻性研究中，90天mRS 0-2比较的森林图
补充图25：前瞻性研究中，90天死亡率比较的森林图

【研究目的】与单纯药物治疗相比，支架取栓器（stent retriever, SR）血栓切除术可改善急性缺血性卒中患者的临床结局，但不同支架取栓器之间的疗效差异尚未明确。本研究开展系统评价与Meta分析，比较EmboTrap、Solitaire™及Trevo三种支架取栓器的临床结局。

【研究方法】本研究遵循PRISMA规范开展系统评价，纳入2014年后发表于PubMed/MEDLINE的英文文献，纳入标准为研究纳入≥25名接受支架取栓术的患者。本研究的结局指标包括：功能与安全性结局（90天改良Rankin量表评分mRS 0-2、死亡率、症状性颅内出血（symptomatic intracranial hemorrhage, sICH）及新区域栓塞（embolization to new territory, ENT））、再通结局（改良脑梗死溶栓分级（modified thrombolysis in cerebral infarction, mTICI）及首次通过再通（first-pass recanalization, FPR））。本研究采用随机效应Meta分析比较各组结局，并通过亚组分析及异常值影响分析探索研究间异质性。

【研究结果】本研究共纳入51项文献，涉及9804名患者。与Trevo组（50.0%，P=0.013）及Solitaire组（45.3%，P<0.001）相比，EmboTrap组的90天mRS 0-2率（57.4%）显著更高。与Solitaire组（20.4%）相比，EmboTrap组（11.2%，P<0.001）与Trevo组（14.5%，P=0.018）的死亡率显著更低。与Solitaire组（7.7%）相比，EmboTrap组（3.9%，P=0.028）与Trevo组（4.6%，P=0.049）的症状性颅内出血率显著更低。三组的新区域栓塞率无显著统计学差异（EmboTrap组6.0%，Trevo组5.3%，Solitaire组7.7%，P=0.518）。EmboTrap组的再通率数值上更高，但未达到统计学显著性差异。

【研究结论】本系统评价与Meta分析结果显示，相较于Solitaire与Trevo，EmboTrap可能与更优的功能结局相关；相较于Solitaire，EmboTrap与Trevo可能与更低的症状性颅内出血率及死亡率相关。三组的再通率及新区域栓塞率无显著统计学差异。受限于本研究的诸多局限性（如领域内血栓切除术技术的异质性），本研究结论需谨慎解读，未来需开展多臂随机对照试验（randomized controlled trial, RCT）比较不同支架取栓器以验证本研究结果。