scholarly journals Endovascular thrombectomy without versus with intravenous thrombolysis in acute ischemic stroke: a non-inferiority meta-analysis of randomized clinical trials

2021 ◽  
pp. neurintsurg-2021-017667
Author(s):  
Chun-Hsien Lin ◽  
Jeffrey L Saver ◽  
Bruce Ovbiagele ◽  
Wen-Yi Huang ◽  
Meng Lee

ObjectiveTo conduct a meta-analysis of randomized trials to comprehensively compare the effect of endovascular thrombectomy (EVT) versus intravenous thrombolysis (IVT) plus EVT on functional independence (modified Rankin Scale (mRS) 0–2) after acute ischemic stroke due to large vessel occlusions (AIS-LVO).MethodsWe searched Pubmed, EMBASE, CENTRAL, and clinicaltrials.gov from January 2000 to February 2021 and abstracts presented at the International Stroke Conference in March 2021 to identify trials comparing EVT alone versus IVT plus EVT in AIS-LVO. Five non-inferiority margins established in the literature were assessed: −15%, −10%, −6.5%, −5%, and −1.3% for the risk difference for functional independence at 90 days.ResultsFour trials met the selection criteria, enrolling 1633 individuals, with 817 participants randomly assigned to EVT alone and 816 to IVT plus EVT. Crude cumulative rates of 90-day functional independence were 46.0% with EVT alone versus 45.5% with IVT plus EVT. Pooled results showed the risk difference of functional independence was 1% (95% CI −4% to 5%) between EVT alone versus IVT plus EVT. The lower 95% CI bound of −4% fell within the non-inferiority margins of −15%, −10%, −6.5%, and −5%, but not −1.3%. Pooled results also showed the risk difference between EVT alone versus IVT plus EVT was 1% (95% CI −3% to 5%) for mRS 0–1, and 1% (95% CI −1% to 3%) for symptomatic intracranial hemorrhage.ConclusionsThis meta-analysis suggests that EVT alone is non-inferior to IVT plus EVT for several, but not the most stringent, non-inferiority margins.

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Georgios Tsivgoulis ◽  
Aristeidis H Katsanos ◽  
Ramin Zand ◽  
Vijay K Sharma ◽  
Martin Köhrmann ◽  
...  

Background & Purpose: In a recent randomized controlled trial (RCT) of intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) antiplatelet pre-treatment (APP) was associated with adverse outcomes. We conducted a systematic review and meta-analysis of available RCTs to investigate the association of APP with outcomes of AIS patients treated with IVT. Methods: The outcome events of interest included symptomatic intracranial hemorrhage (sICH), complete recanalization (CR), 3-month favorable functional outcome (FFO, mRS-score: 0-1), functional independence (FI, mRS-score: 0-2), and mortality. Both unadjusted and adjusted (for baseline stroke severity and age) analyses were performed using random effects methodology. Results: We included 8 RCTs (5,332 total patients, 34% with APP). In unadjusted analyses (Figure 1), APP was associated with higher likelihood of sICH (OR=2.01, 95%CI: 1.53-2.63) and death (OR=1.59, 95%CI: 1.24-2.03; 1C) and lower likelihood of 3-month FI (OR=0.69, 0.56-0.85). No association was detected between APP and 3-month FFO (OR=0.79, 95%CI: 0.58-1.07) and CR (OR=0.64, 95%CI: 0.04-11.66). In adjusted analyses (Figure 2), APP was related to higher odds of sICH (OR=1.89, 95%CI: 1.14-3.12). There was no association between APP and 3-month FI (OR=0.94, 95%CI: 0.70-1.26) or death (OR=1.01, 95%CI: 0.55-1.86). In all analyses no evidence of heterogeneity was detected. Conclusion: Despite APP association with a higher risk of sICH after thrombolysis, three-month functional outcomes appear un-affected by APP. APP before IVT should not be used as an excuse to withhold or to lower the dose of IVT.


2021 ◽  
Vol 12 ◽  
Author(s):  
Jing Chen ◽  
Teng-Fei Wan ◽  
Tian-Ce Xu ◽  
Guo-Can Chang ◽  
Hui-Sheng Chen ◽  
...  

Background and purpose: It is unclear whether endovascular thrombectomy alone compared with intravenous thrombolysis combination with endovascular thrombectomy can achieve similar neurological outcomes in patients with acute large vessel occlusion stroke. We aimed to perform a systematic review and meta-analysis of randomized controlled trials to compare endovascular thrombectomy alone or intravenous thrombolysis plus endovascular thrombectomy in this population.Methods: We systematically searched PubMed, Embase, and ClinicalTrials.gov. We restricted our search to randomized clinical trials that examined the clinical outcomes of endovascular thrombectomy alone vs. intravenous thrombolysis plus endovascular thrombectomy. The Cochrane risk of bias tool was used to assess study quality. Random-effects meta-analyses were used for evaluating all outcomes.Results: Total three randomized controlled trials with 1,092 individuals enrolled were included in the meta-analysis, including 543 (49.7%) who received endovascular thrombectomy alone and 549 (50.3%) who received intravenous thrombolysis plus endovascular thrombectomy. The primary outcome of 90-day functional independence (modified Rankin scale (mRS) score ≤ 2) was 44.6% (242/543) in the endovascular thrombectomy alone group vs. 42.8% (235/549) in the alteplase with endovascular thrombectomy group (odds ratio (OR), 1.08 [95% CI, 0.85–1.38]; P = 0.0539). Among pre-specified secondary outcomes, no significant between-group differences were found in excellent outcome (mRS score ≤ 1) (OR, 1.12 [95% CI, 0.85–1.47]; P = 0.418), mortality at 90 days (OR, 0.93 [95% CI, 0.68–1.29]; P = 0.673), successful reperfusion (thrombolysis in cerebral infarction 2b-3) (OR, 0.75 [95% CI, 0.54–1.05]; P = 0.099), and symptomatic intracranial hemorrhage (OR, 0.72 [95% CI, 0.45–1.15]; P = 0.171).Conclusions: Among patients with acute ischemic stroke in the anterior circulation within 4.5 h from the onset, endovascular thrombectomy alone was non-inferior to combined intravenous thrombolysis and endovascular thrombectomy.


Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Mikito Hayakawa ◽  
Masatoshi Koga ◽  
Shoichiro Sato ◽  
Shoji Arihiro ◽  
Yoshiaki Shiokawa ◽  
...  

Objective: Although intravenous thrombolysis (IVT) using alteplase for octogenarians with acute ischemic stroke becomes relatively familiar, it is unclear whether IVT for nonagenarians is a futile intervention. The purpose of this study is to clarify the efficacy and safety of IVT using low-dose alteplase (0.6 mg/kg) for nonagenarians compared with octogenarians. Methods: Stroke Acute Management with Urgent Risk-factor Assessment and Improvement (SAMURAI) rtPA registry retrospectively collected 600 consecutive acute stroke patients receiving IVT from 10 Japanese stroke centers between October 2005 and July 2008. We extracted all octogenarians (O group) and nonagenarians (N group) from the registry. We compared baseline characteristics, symptomatic intracranial hemorrhage (SICH), and 3-month outcomes between the groups. 3-month outcomes include; functional independence (FI) defined as a mRS score 0-2, good outcome (GO) as a mRS score 0-2 or same as the premorbid mRS, poor outcome (PO) defined as a mRS score 5-6, and death. Results: Twenty-five nonagenarians (mean age, 93 years) and 124 octogenarians (mean age, 84 years) were included. N group was more female-predominant (76% versus 56%, p=0.06) and premorbidly dependent (44% versus 14%, p<0.001) than O group. There were no significant differences of median baseline NIHSS score (16 versus 14, p=0.95) and Alberta Stroke Program Early CT Score (9 versus 9, p=0.36) between the groups. The rate of FI tended to be lower in N group than O group (16% versus 36%, p=0.06), otherwise, the differences of the rates of GO (28% versus 37%, p=0.39), PO (40% versus 36%, p=0.73), death (20% versus 11%, p=0.23) and SICH (0% versus 2.4%, p=1.00) were not significant between the groups. In comparison with O group, N group was not associated with 3-month clinical outcomes (FI; OR 0.61; 95% CI, 0.15-2.42, GO; 0.98; 0.31-3.07, PO; 0.63; 0.15-2.70, death; 3.18; 0.62-16.3) and SICH (0.68; 0.17-2.69) after multivariate adjustment. Conclusions: IVT using low-dose alteplase for N group resulted in less frequent achievement of FI mainly because of more premorbid dependency than O group, however, showed at least a similar safety and a potential efficacy.


2021 ◽  
pp. 174749302110473
Author(s):  
Jin Pyeong Jeon ◽  
Chih-Hao Chen ◽  
Fon-Yih Tsuang ◽  
Jianming Liu ◽  
Michael D Hill ◽  
...  

Background. The impact of renal impairment (RI) on the outcomes of patients with acute ischemic stroke (AIS) treated with endovascular thrombectomy (EVT) was relatively limited and contradictory. We performed a systematic review and meta-analysis to investigate this. Aims. We registered a protocol on September 2020 and searched MEDLINE, EMBASE, and Google Scholar accordingly. RI was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2. Predefined outcomes included functional independence (defined as a modified Rankin Scale of 0, 1, or 2) at 3 months, successful reperfusion, mortality, and symptomatic intracerebral hemorrhage (sICH). Summary of review. Eleven studies involving 3453 patients were included. For the unadjusted outcomes, RI was associated with fewer functional independence (odds ratio (OR), 0.49; 95% confidence interval (CI), 0.39–0.62) and higher mortality (OR, 2.55; 95% CI, 2.03–3.21). RI was not associated with successful reperfusion (OR, 0.80; 95% CI 0.63–1.00) and sICH (OR, 1.41; 95% CI, 0.95–2.10). For the adjusted outcomes, results derived from a multivariate meta-analysis were consistent with the respective unadjusted outcomes: functional independence (OR, 0.59; 95% CI, 0.45–0.77), mortality (OR, 2.23, 95% CI, 1.45–3.43), and sICH (OR, 1.34; 95% CI, 0.85–2.10). Conclusions. We presented the first systematic review to demonstrate that RI is associated with fewer functional independence and higher mortality. Future EVT studies should publish complete renal eGFR data to facilitate prognostic studies and permit eGFR to be analyzed in a continuous variable. Systematic Review Registration: PROSPERO CRD42020191309


2019 ◽  
Vol 12 (3) ◽  
pp. 266-270 ◽  
Author(s):  
Eric S Sussman ◽  
Blake Martin ◽  
Michael Mlynash ◽  
Michael P Marks ◽  
David Marcellus ◽  
...  

IntroductionMultiple randomized trials have shown that endovascular thrombectomy (EVT) leads to improved outcomes in acute ischemic stroke (AIS) due to large vessel occlusion (LVO). Elderly patients were poorly represented in these trials, and the efficacy of EVT in nonagenarian patients remains uncertain.MethodsWe performed a retrospective cohort study at a single center. Inclusion criteria were: age 80–99, LVO, core infarct <70 mL, and salvageable penumbra. Patients were stratified into octogenarian (80–89) and nonagenarian (90–99) cohorts. The primary outcome was the ordinal score on the modified Rankin Scale (mRS) at 90 days. Secondary outcomes included dichotomized functional outcome (mRS ≤2 vs mRS ≥3), successful revascularization, symptomatic intracranial hemorrhage (ICH), and mortality.Results108 patients met the inclusion criteria, including 79 octogenarians (73%) and 29 nonagenarians (27%). Nonagenarians were more likely to be female (86% vs 58%; p<0.01); there were no other differences between groups in terms of demographics, medical comorbidities, or treatment characteristics. Successful revascularization (TICI 2b–3) was achieved in 79% in both cohorts. Median mRS at 90 days was 5 in octogenarians and 6 in nonagenarians (p=0.09). Functional independence (mRS ≤2) at 90 days was achieved in 12.5% and 19.7% of nonagenarians and octogenarians, respectively (p=0.54). Symptomatic ICH occurred in 21.4% and 6.4% (p=0.03), and 90-day mortality rate was 63% and 40.9% (p=0.07) in nonagenarians and octogenarians, respectively.ConclusionsNonagenarians may be at higher risk of symptomatic ICH than octogenarians, despite similar stroke- and treatment-related factors. While there was a trend towards higher mortality and worse functional outcomes in nonagenarians, the difference was not statistically significant in this relatively small retrospective study.


2021 ◽  
Vol 26 (4) ◽  
pp. 671-683
Author(s):  
YinQin Hu ◽  
YangBo Hou ◽  
Zhen Chen ◽  
Qian Xiao ◽  
Huixia Chen ◽  
...  

Background: Intravenous thrombolysis is the preferred clinical treatment for acute ischemic stroke. Alteplase is an intravenous thrombolytic drug used in clinical practice. Recently, studies have shown the efficacy of another intravenous thrombolytic drug, tenecteplase, and have reported that the risk of bleeding is low. However, at present, Chinese and international research has yielded controversial results regarding the efficacy and risks of tenecteplase. Therefore, this systematic review and meta- analysis of the efficacy and safety of tenecteplase were performed. Methods: PubMed, the Cochrane Library, MEDLINE, the Wanfang Database and CNKI were searched for all studies on the thrombolytic treatment of acute ischemic stroke. All studies published in English prior to March 2021 were retrieved. The studies were screened and selected based on the inclusion and exclusion criteria. Then, the data were extracted and recorded by trained researchers. RevMan 5.4 statistical software was used to analyze the data on the 24h recanalization rate, early neurological improvement (24h reduction in the National Institutes of Health Stroke Scale [NIHSS] score of at least 8 points or 24 h NIHSS score of 0~1 point), mRS score at 90 days, intracranial hemorrhage, symptomatic intracranial hemorrhage and mortality in the tenecteplase group and alteplase group. Results: A total of 565 related studies were identified through the initial searches in each database. The citations of meta-analyses and related reviews were screened for additional eligible articles. Eventually, 9 high-quality English-language articles that included 2149 patients with acute ischemic stroke (including 1035 in the tenecteplase group and 1046 in the alteplase group)were included in this meta-analysis. The meta-analysis results were as follows: (1) Efficacy: The 24 h recanalization rate with regard to vascular recanalization was significantly better in the tenecteplase group than in the alteplase group(OR = 1.83, 95% CI: 1.23~2.72, z = 2.97, P = 0.003). There was significantly greater improvement in early neurological function in the tenecteplase group than in the alteplase group (OR= 1.34, 95% CI: 1.11~1.63, Z=3.00, P =0.003). There were no significant differences in 90-day mRS scores between the two groups (mRS score =0-1, OR = 1.20, 95% CI: 0.99~1.46, z = 1.82, p = 0.07; mRS score =0-2, OR = 1.17, 95% CI: 0.94~1.45, z = 1.38, p = 0.17). However, the subgroup analysis showed that the 90-day mRS score of the 0.25 mg/kg tenecteplase group was significantly different from that of groups treated with other doses of tenecteplase (OR = 1.48, 95% CI: 1.01~2.03, z = 2.03, p = 0.04). (2) Safety: The incidences of any intracranial hemorrhage (OR = 0.91, 95% Ci: 0.55~1.49, z = 0.39, p = 0.70), symptomatic intracranial hemorrhage (OR = 1.21, 95% CI: 0.63~2.32, z = 0.56 P = 0.57), and mortality (OR = 0.85, 95% CI: 0.57~1.26, z = 0.82, p = 0.41) were not significantly different between the tenecteplase and alteplase groups. Conclusions: Tenecteplase can significantly increase the 24-hour vascular recanalization rate and improve the neurological prognosis of patients with acute ischemic stroke and it does not increase the risk of intracranial hemorrhage or mortality.


2019 ◽  
Author(s):  
Massimo Gamba ◽  
Nicola Gilberti ◽  
Enrico Premi ◽  
Angelo Costa ◽  
Michele Frigerio ◽  
...  

Abstract Background and Purpose endovascular therapy (ET) is the standard of care for anterior circulation acute ischemic stroke (AIS) caused by large vessel occlusion (LVO). The role of adjunctive intravenous thrombolysis (IVT) in these patients is still unclear. The present study aims to test whether IVT plus ET (CoT, combined therapy) provides additional benefits over direct ET for anterior circulation AIS by LVO. Methods we performed a single center retrospective observational study of patients with AIS caused by anterior circulation LVO, referred to our center between January 2014 and January 2017 and treated with ET. The patients were divided in 2 groups based on the treatment they received: CoT and, if IVT contraindicated, direct ET. We compared functional recovery (modified Rankin at 3-months follow-up), recanalization rate (thrombolysis in cerebral infarction [TICI] score) and time, early follow-up infarct volume (EFIV) (for recanalized patients only) as well as safety profile, defined as symptomatic intracerebral hemorrhage (sICH) and 3-month mortality, between groups. Results 145 subjects were included in the study, 70 in direct ET group and 75 in CoT group. Patients who received CoT presented more frequently a functional independence at 3-months follow-up compared to patients who received direct ET (mRS score 0-1: 48.5% vs 18.6%; P<0.001. mRS score 0-2: 67.1% vs 37.3%; P<0.001), higher first-pass success rate (62.7% vs 38.6%, P<0.05), higher recanalization rate (84.3% vs 65.3%; P=0.009) and, in recanalized subjects, smaller EFIV (16.4ml vs 62.3ml; P=0.003). The safety profile was similar for the 2 groups. In multivariable regression analysis, low baseline NIHSS score (P<0.05), vessel recanalization (P=0.05) and CoT (P=0.03) were indipendent predictors of 3-month favorable outcome. Conclusions CoT appears more effective than ET alone for anterior circulation AIS with LVO, with similar safety profile.


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Georgios Tsivgoulis ◽  
Aristeidis H Katsanos ◽  
Dimitris Mavridis ◽  
Anne W Alexandrov ◽  
Georgios Magoufis ◽  
...  

Background & Purpose: Current AHA recommendations advocate that pretreatment with intravenous thrombolysis (IVT) should first be offered to all eligible acute ischemic stroke (AIS) patients with emergent large vessel occlusion (ELVO) before an endovascular thrombectomy (ET) procedure. Nevertheless, recent single-center observational studies question the utility of IVT pretreatment in ELVO patients eligible for systemic thrombolysis and advocate ET monotherapy. We sought to evaluate the comparative efficacy between ET and bridging therapy (IVT&ET) in AIS due to ELVO. Methods: We performed mixed-effects subgroup analyses, according to IVT pretreatment status of both functional independence [modified Rankin Scale (mRS) of 0-2)] and death/dependency (mRS of 5-6) at 90 days using available RCTs that evaluated the safety and efficacy of ET with stent-retrievers in comparison to standard therapy. We additionally performed an ordinal logistic regression analysis of individual patient data on the distribution of 3-month mRS scores (shift analysis) between the two groups. Results: We identified 7 eligible RCTs including 1764 ELVO patients (53% men), and 108 patients randomized to ET without IVT pretreatment. Patients receiving bridging therapy (BT) had lower rates (p=0.041) of 90-day death/dependency (19%, 95%CI: 14%-25%) compared to patients receiving only ET (31%, 95%CI: 21%-43%; Figure). Similarly, shift-analysis favored a trend for BT over ET in terms of better 90-day functional outcome (common OR=0.78, 95%CI: 0.53-1.10; p=0.155). Conclusion: Our findings indicate that pretreatment with IVT prior ET in ELVO patients may be associated with lower rates of three-month death/dependency and a trend towards more favorable functional outcomes. Until the results from head-to-head RCTs comparing BT to ET monotherapy become available, our findings support AHA guidelines recommending delivery of tPA to appropriate ELVO candidates undergoing ET.


2021 ◽  
pp. neurintsurg-2021-017928
Author(s):  
Jian Zhang ◽  
Shijian Chen ◽  
Shengliang Shi ◽  
Yueling Zhang ◽  
Deyan Kong ◽  
...  

ObjectiveIn this review and meta-analysis we sought to compare the efficacy and safety of direct endovascular thrombectomy (EVT) and bridging therapy for intravenous thrombolysis (IVT)-eligible patients with acute ischemic stroke caused by large vessel occlusions (AIS-LVO).MethodsWe searched Medline, Embase, and the Cochrane Library for published randomized clinical trials (RCTs) and observational studies providing outcomes of patients with IVT-eligible AIS-LVO who have undergone EVT with or without IVT. The primary outcome was the proportion of patients achieving a modified Rankin Scale (mRS) score of 0–2 at 90 days. The secondary outcomes included the rates of (1) an excellent outcome defined as an mRS score of 0 or 1 at 90 days, (2) mortality at 90 days, (3) symptomatic intracranial hemorrhage (sICH), (4) any type of intracranial hemorrhage (ICH), (5) successful recanalization, and (6) clot migration.ResultsWe included three RCTs and six observational studies (4 of which were propensity score-adjusted studies) with a total of 3133 patients. In unadjusted and adjusted analyses, no differences in the rates of mRS scores 0–2, mRS scores 0–1, mortality at 90 days, sICH or successful recanalization were detected between patients with AIS-LVO who underwent direct EVT or bridging therapy. The patients treated with direct EVT had a lower risk ratio for any type of ICH and clot migration than did the patients treated with bridging therapy.ConclusionCompared with bridging therapy, direct EVT may be equally effective and yield a lower rate of ICH and clot migration in patients with AIS.Trail registration numberPROSPERO: CRD42021236691.


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