scholarly journals Tenecteplase versus alteplase for acute ischemic stroke thrombolysis: a systematic review and meta-analysis

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.

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.


2018 ◽  
Vol 11 (1) ◽  
pp. 14-19 ◽  
Author(s):  
Mohammad Ismail ◽  
Xavier Armoiry ◽  
Noam Tau ◽  
François Zhu ◽  
Udi Sadeh-Gonik ◽  
...  

BackgroundThe effectiveness of mechanical thrombectomy (MT) in acute ischemic stroke due to large vessel occlusion is time-dependent. While only stroke centers with endovascular capabilities perform MT, many patients who had a stroke initially present to the closest primary stroke centers capable of administering earlier intravenous thrombolysis, and then require to be transferred to a comprehensive stroke center for MT.PurposeTo compare the outcomes of this care pathway (drip and ship (DS)) with that whereby patients are directly transferred to a comprehensive stroke center (mothership (MS)).MethodsWe performed a systematic review and meta-analysis of published studies using several electronic databases to determine whether successful reperfusion (modified Thrombolysis In Cerebral Infarction ≥2b), functional independence at 90 days (modified Rankin Scale score ≤2), symptomatic intracranial hemorrhage, and 90-day mortality differed between those who underwent MT with the DS or the MS treatment pathway. Outcomes were meta-analyzed and the results expressed as adjusted relative risk (aRR) for the primary analysis and unadjusted relative risk (uRR) for secondary analysis.ResultsEight studies including 2068 patients were selected, including one study reporting results fully adjusted for baseline characteristics. Patients undergoing MS had better functional independence than those undergoing DS (uRR=0.87, 95% CI 0.81 to 0.93; aRR=0.87, 95% CI 0.77 to 0.98). No difference was found between the treatment pathways in successful reperfusion (uRR=1.05, 95% CI 0.95 to 1.15; aRR=1.00, 95% CI 0.92 to 1.10), symptomatic intracranial hemorrhage (uRR=1.37, 95% CI 0.91 to 2.06; aRR, 1.53, 95% CI 0.79 to 2.98), and 90-day mortality (uRR=1.00, 95% CI 0.84 to 1.19; aRR=1.21, 95% CI 0.89 to 1.64).ConclusionsPatients who had an acute ischemic stroke admitted directly to a comprehensive stroke center (MS patients) with endovascular capacities may have better 90-day outcomes than those receiving DS treatment. However, major limitations of current evidence (ie, retrospective studies and selection bias) suggest a need for adequately powered studies. Multicenter randomized controlled trials are expected to answer this question.


Author(s):  
Houwei Du ◽  
Hanhan Lei ◽  
Gareth Ambler ◽  
Shuangfang Fang ◽  
Raoli He ◽  
...  

Background Whether intravenous thrombolysis before mechanical thrombectomy provides additional benefit for functional outcome in acute ischemic stroke remains uncertain. We performed a meta‐analysis to compare the outcomes of direct mechanical thrombectomy (dMT) to mechanical thrombectomy with bridging using intravenous thrombolysis (bridging therapy [BT]) in patients with acute ischemic stroke. Methods and Results We performed a literature search in the PubMed, Excerpta Medica database, and Cochrane Central Register of Controlled Trials from January 1, 2003, to April 26, 2021. We included randomized clinical trials and observational studies that reported the 90‐day functional outcome in patients with acute ischemic stroke undergoing dMT compared with BT. The 12 included studies (3 randomized controlled trials and 9 observational studies) yielded 3924 participants (mean age, 68.0 years [SD, 13.1 years]; women, 44.2%; 1887 participants who received dMT and 2037 participants who received BT). A meta‐analysis of randomized controlled trial and observational data revealed similar 90‐day functional independence (odds ratio [OR], 1.04; 95% CI, 0.90–1.19), mortality (OR, 1.03; 95% CI, 0.78–1.36), and successful recanalization (OR, 0.93; 95% CI, 0.76–1.14) for patients treated with dMT or BT. Compared with those in the BT group, patients in the dMT group were less likely to experience symptomatic intracranial hemorrhage (OR, 0.68; 95% CI, 0.51–0.91; P =0.008) or any intracranial hemorrhage (OR, 0.71; 95% CI, 0.61–0.84; P <0.001). Conclusions In this meta‐analysis of patients with acute ischemic stroke, we found no significant differences in 90‐day functional outcome or mortality between dMT and BT, but a lower rate of symptomatic intracranial hemorrhage for dMT. These findings support the use of dMT without intravenous thrombolysis bridging therapy. Registration URL: https://www.crd.york.ac.uk/prospero/ ; Unique identifier: 42021234664.


2021 ◽  
Vol 19 ◽  
Author(s):  
Xiaohua Xie ◽  
Jie Yang ◽  
Lijie Ren ◽  
Shiyu Hu ◽  
Wancheng Lian ◽  
...  

Background: Symptomatic intracranial hemorrhage (sICH) is a serious hemorrhagic complication after intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients. Most existing predictive scoring systems were derived from Western countries Objective: To develop a nomogram to predict the possibility of sICH after IVT in an Asian population. Methods: This retrospective cohort study included AIS patients treated with recombinant tissue plasminogen activator (rt-PA) in a tertiary hospital in Shenzhen, China, from January 2014 to December 2020. The end point was sICH within 36 hours of IVT treatment. Multivariable logistic regression was used to identify risk factors of sICH, and a predictive nomogram was developed. Area under the curve of receiver operating characteristic curves (AUC), calibration curve, and decision curve analyses were performed. The nomogram was validated by bootstrap resampling Results: Data on a total of 462 patients were collected, of whom 20 patients (4.3%) developed sICH. In the multivariate logistic regression model, the National Institute of Health stroke scale scores (NIHSS) (odds ratio [OR], 1.14; 95% confidence interval [CI], 1.06–1.23, P < 0.001), onset to treatment time (OTT) (OR, 1.02; 95% CI, 1.01–1.03, P < 0.001), neutrophil to lymphocyte ratio (NLR) (OR, 1.22; 95% CI, 1.09–1.35, P < 0.001), and cardioembolism (OR, 3.74; 95% CI, 1.23–11.39, P = 0.020) were independent predictors for sICH and were used to construct a nomogram. Our nomogram exhibited favorable discrimination ability [AUC, 0.878; specificity, 87.35%; and sensitivity, 73.81%]. Bootstrapping for 500 repetitions was performed to further validate the nomogram. The AUC of the bootstrap model was 0.877 (95% CI: 0.823–0.922). The calibration curve exhibited good fit and calibration. The decision curve revealed good positive net benefits and clinical effects Conclusion: The nomogram consisted of the predictors NIHSS, OTT, NLR, and cardioembolism could be used as an auxiliary tool to predict the individual risk of sICH in Chinese AIS patients after IVT. Further external verification among more diverse patient populations is needed to demonstrate the accuracy of the model’s predictions.


2019 ◽  
Vol 21 (9) ◽  
pp. 1181-1188 ◽  
Author(s):  
Peng Zhang ◽  
Zhen-Ni Guo ◽  
Xin Sun ◽  
Yingkai Zhao ◽  
Yi Yang

Abstract Introduction The existence of the smoker’s paradox is controversial and potential mechanisms have not been explained. We aimed to explore the association between cigarette smoking and functional outcome at 3 months in patients with acute ischemic stroke who were treated with intravenous thrombolysis (IVT) or endovascular treatment (EVT). Methods This meta-analysis was conducted in accordance with the PRISMA guidelines. Studies exploring the association between smoking and good functional outcome (modified Rankin Scale score ≤ 2) following IVT or EVT were searched via the databases of PubMed, Embase, and the Cochrane Library from inception to August 8, 2018. Information on the characteristics of included studies was independently extracted by two investigators. Data were pooled using a random-effects or fixed-effects meta-analysis according to the heterogeneity of included studies. Results Among 20 identified studies, 15 reported functional outcomes following IVT, and five reported functional outcomes following EVT. Unadjusted analyses showed that smoking increased the odds of good functional outcomes with a pooled odds ratio (OR) of 1.48 (95% confidence interval [CI]: 1.36–1.60) after IVT and 2.10 (95% CI: 1.47–3.20) after EVT. Of IVT studies, only eight reported outcomes adjusted for covariates and none of the EVT studies reported adjusted outcomes. After adjustment, the relation between smoking and good functional outcome following IVT lost statistical significance (OR 1.14 [95% CI: 0.81–1.59]). Conclusion Our meta-analysis suggested that smoking was not associated with good functional outcome (mRS ≤ 2) at 3 months in patients with acute ischemic stroke who were treated with intravenous thrombolysis. Implications The existence of the smoker’s paradox is controversial. A previous letter by Plas et al. published in 2013 reported a positive result for the association between smoking and good functional outcome at 3 months in acute ischemic stroke patients who received intravenous thrombolysis (IVT). However, a major limitation of their meta-analysis was that the process of data synthesis was based on unadjusted data. Therefore, we conducted this meta-analysis to investigate the association based on adjusted data and a larger sample size. Our meta-analysis suggested that smoking was not associated with good functional outcome after adjusting for covariates.


Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Reza Bavarsad Shahripour ◽  
Benjamin Shifflett ◽  
Edward Labin ◽  
Morgan Figurelle ◽  
Anna Barminova ◽  
...  

Background: Patients with acute ischemic stroke (AIS) due to atrial fibrillation (afib) may have increased complications from intravenous thrombolysis or endovascular treatment (ET) compared to other stroke subtypes. The purpose of this study was to compare the rates of symptomatic intracranial hemorrhage (sICH) in patients with and without a history of a fib treated with IV rt-PA and/or ET. Methods: Consecutive stroke code activations were retrospectively analyzed from January 2004-June 2020 at an academic comprehensive stroke center. Patients were included if they were treated with IV rt-PA and/or ET within 24 hours of stroke onset. Patients were stratified into the six groups:1-No hx of a fib with ET only, 2-Hx of a fib with ET only, 3-No hx of a fib with IV rt-PA plus ET, 4-Hx of a fib with IV rt-PA plus ET, 5-No hx of a fib with IV rt-PA only, 6-Hx of a fib with IV rt-PA only. Primary outcome was defined as any sICH within 72 hours of treatment using the NINDS definition. Baseline demographics were compared. Chi squared was used to assess differences in sICH rates and logistic regression to compare individual groups. Analyses were both unadjusted and adjusted for baseline NIHSS, age, sex, baseline blood pressure, pre-stroke mRS, smoking status, and baseline glucose. Results: We identified 720 AIS patients who received acute treatment (IV rt-PA: n=578; ET: n=100; IV rt-PA+ET:n=18). There was a significant difference in sex (p=0.005); Hispanic ethnicity (p=0.002); current smoking (p=<0.001); current alcohol use (p=0.03), CHF (p=0.01); and age (p<0.0001) between groups. Baseline NIHSS was significantly higher in Group 4 (23, SD 8, p=<0.001).In adjusted analysis, there was no significant difference in sICH in patients with a fib after receiving IVtPA (OR 1.53, CI 0.47-4.99, p=0.48), ET (OR 0.93 , CI 0-∞, p=1.00), or both (OR 0.25,CI 0.00-9.07, p=0.45) compared to those without afib. There was no significant difference in sICH in adjusted analyses in patients with and without a fib overall (OR 0.93, CI 0-∞, p=1.00). Conclusion: In this study, atrial fibrillation did not have a significant impact on rates of sICH in AIS patients treated with IV rt-PA, ET, or both. This study supports the safety of IV rt-PA, ET, and combination therapy in the atrial fibrillation population.


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