scholarly journals Efficacy and Safety of rt-PA Intravenous Thrombolysis in Patients with Wake-up Stroke: A Meta-Analysis

Author(s):  
Hongfa Liu ◽  
Jianghong Luo ◽  
Fang Zhang ◽  
Ziliang Zhang ◽  
Wei Gu ◽  
...  

Abstract Background Recombinant tissue plasminogen activator (rt-PA) is one of the most effective therapies for patients with acute ischemic stroke. However, wake-up stroke (WUS) is typically excluded from intravenous thrombolytic therapy because the time of symptom onset is unclear. Therefore, we aimed to assess the efficacy and safety of rt-PA intravenous thrombolysis in patients with WUS by meta-analysis. Methods We completed a systematic literature search of PubMed, Embase, the Cochrane Library, and SinoMed and included relevant studies of WUS patients covering rt-PA thrombolysis and nonthrombolysis (published from January 1, 2000, to February 28, 2021, with no language restrictions). Primary outcomes included safety outcomes and functional outcomes. Safety outcomes was measured according to the incidence of symptomatic intracranial hemorrhage (SICH) and mortality within 90 days. Efficacy outcomes was measured based on 90-day modified Rankin Scale (mRS) score. We assessed pooled data using either a random-effects model (when P < 0.10, I2 > 50%) or a fixed-effects model (when P > 0.10, I2 < 50%). Results Nine studies with 913 patients were included in the meta-analysis. All patients had ischemic stroke confirmed by computed tomography or magnetic resonance imaging. The incidence of mRS 0–2 was significantly higher in the rt-PA thrombolysis group compared with the nonthrombolysis group. And rt-PA thrombolytic WUS patients did not differ significantly from nonthrombolytic WUS patients in terms of 90-day mortality. However, the rate of SICH was also significantly higher in the rt-PA thrombolysis group than that in the nonthrombolysis group. Conclusions Patients with WUS who received rt-PA thrombolysis had a significant positive effect within 90 days. In addition, although there is no significant increase in mortality, we need to be aware of the risk of intracranial hemorrhage transformation associated with rt-PA thrombolysis despite no obvious increase in mortality. The safety of rt-PA intravenous thrombolysis should be closely monitored in patients with WUS.

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Danfeng Zhang ◽  
Yan Dong ◽  
Ya Li ◽  
Jigang Chen ◽  
Junyu Wang ◽  
...  

Cerebrolysin was reported to be effective in the neurological improvement of patients with acute ischemic stroke (AIS) in experimental models, while data from clinical trials were inconsistent. We performed a meta-analysis to explore the efficacy and safety of cerebrolysin for AIS. PubMed, EMBASE, and Cochrane Library were searched for randomized controlled trials, which intervened within 72 hours after the stroke onset. We investigated the efficacy and safety outcomes, respectively. Risk ratios and mean differences were pooled with fixed-effects model or random-effects model. Seven studies were identified, involving 1779 patients with AIS. The summary results failed to demonstrate significant superiority of cerebrolysin in the assessment of efficacy outcomes of mRS and BI. Similarly, administration of cerebrolysin had neutral effects on safety outcomes compared with placebo, including mortality and SAE. However, the number of included studies was small, especially in the analysis of efficacy outcomes, which might cause publication bias and inaccurate between-studies variance in the meta-analysis. Conclusively, although it seemed to be safe, routine use of cerebrolysin to improve the long-term rehabilitation after stroke could not be supported by available evidence.


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 ◽  
Vol 121 (8) ◽  
pp. 841-848 ◽  
Author(s):  
Shuo Zhang ◽  
Fengxiao Zhang ◽  
Meng Du ◽  
Kun Huang ◽  
Cheng Wang

AbstractFe therapy can be effective in heart failure patients both with and without anaemia. However, the role of Fe therapy in such patients is still uncertain. In this review, the aim was to evaluate the efficacy and safety of Fe therapy in adult patients with heart failure who have reduced ejection fraction (HFrEF). Multiple databases (PubMed, Medline, EMBASE, the Cochrane Library and Clinical Trials) were searched up to December 2017 and the reference lists of relevant articles obtained from the search were reviewed. Data extracted from randomised control trials (RCT) selected for the review were pooled using a fixed effects model or a random effects model, according to heterogeneity between trials. Nine RCT were included in this meta-analysis which included a total of 789 patients who received Fe therapy and who in turn were compared with 585 controls. There was significant improvement in the 6-min walk test (19·05 m, 95 % CI 10·48, 27·62) and peak VO2/kg (0·93 ml/kg per min, 95 % CI 0·16, 1·69) in the Fe supplementation arm. With Fe therapy, fewer patients were hospitalised for heart failure (OR: 0·42, 95 % CI 0·27, 0·65), but no relationship was found for total re-hospitalisation (OR: 0·70, 95 % CI 0·32, 1·51) or mortality (OR: 0·70, 95 % CI 0·38, 1·28). Fe therapy has the potential to improve exercise tolerance, reduce re-hospitalisations for patients with HFrEF having Fe deficiency. In addition, Fe supplementation was found to be safe, with no increased rate of adverse events.


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.


2020 ◽  
Author(s):  
Yunzhen Hu ◽  
Chunmei Ji

Abstract Background The efficacy and safety of intravenous thrombolysis (IVT) in acute ischemic stroke with atrial fibrillation (AF) were controversial. Methods We performed a meta-analysis of all relevant studies retrieved by systematic searches of the, Embase, and Cochrane databases up to December 31, 2019. Modified Rankin Scale (mRS) scores 0–1 at 90 days, mRS 0–2 at 90 days, overall mortality, and symptomatic intracranial hemorrhage (sICH) incidence were collected as outcome measures. Fixed effects meta-analytical models were used, and between-study heterogeneity was assessed. Results A total of 8,509 patients were enrolled in eighteen studies. In AF IVT versus non-AF IVT studies, AF was associated with a significant decrease in the proportion of patients with mRS of 0–1 (24.1% vs. 34.5%; OR 0.57; 95% CI 0.50–0.65; P = 0.000), mRS of 0–2 (33.6% vs. 47.8%; OR 0.50; 95% CI 0.44–0.57; P = 0.000) and significant higher in mortality (19.4% vs. 11.5%; OR 2.05; 95% CI 1.79–2.36; P = 0.000) and sICH incidence (6.4% vs. 4.1%; OR 1.60; 95% CI 1.27–2.01; P = 0.000). In AF IVT versus AF non-IVT studies, thrombolysis carried a higher risk of sICH (5.7% vs. 1.6%; OR 3.44; 95% CI 2.04–5.82; P = 0.000) instead of a better prognosis. Subgroup analysis in prospective studies also suggested a poorer functional prognosis and higher mortality in AF patients treated IVT compared with non-IVT. Conclusion Patients with AF had worse outcomes than those without AF after thrombolytic therapy. Patients with AF had a higher incidence of sICH after thrombolysis than those without thrombolysis.


2020 ◽  
Author(s):  
xueyi sun ◽  
xianfei ding ◽  
huoyan liang ◽  
xiaojuan zhang ◽  
shaohua liu ◽  
...  

Abstract Background: Multiple studies have reported that mesenchymal stem cell (MSC) therapy has beneficial effects in experimental models of sepsis. However, this finding remains inconclusive. This study was performed to systematically determine the connection between MSC therapy and mortality in sepsis animal models by pooling and analyzing data from newly published studies. Methods: A detailed search of related studies from 2009 to 2019 was conducted in four databases, including MEDLINE, EMBASE, Cochrane Library, and Web of Science. After browsing and filtering out articles that met the inclusion criteria for statistical analysis, the inverse variance method of the fixed effects model was used to calculate the pooled odds ratios (ORs) and their 95% confidence intervals (CIs). Results: Twenty-nine animal studies, including 1,266 animals, were identified. None of the studies were judged to have a low risk of bias. The meta-analysis demonstrated that MSC therapy was related to a significantly lower mortality rate (OR 0.29, 95% CI 0.22–0.38, P <0.001). Subgroup analyses performed based on the MSC injection dose (<1.0 × 10 6 cells, OR=0.33, 95% CI 0.20–0.56, P <0.001; 1.0 × 10 6 cells, OR=0.24, 95% CI 0.16–0.35, P <0.001) and injection time (<1 hour, OR=0.24, 95% CI 0.13–0.45, P <0.001; 1 hour, OR=0.28, 95% CI 0.17–0.46, P <0.001) demonstrated that treatment with MSCs significantly reduced the mortality rate of animals with sepsis. Conclusion: This up-to-date meta-analysis showed a connection between MSC therapy and lower mortality in sepsis animal models, supporting the potential therapeutic effect of MSC treatment in future clinical trials. The results in this study contradict a previous meta-analysis with regards to the ideal dose of MSC therapy. Thus, further research is required to support these findings.


PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e10859
Author(s):  
Lili Qin ◽  
Yueqi Wang ◽  
Na Yang ◽  
Yangyu Zhang ◽  
Tianye Zhao ◽  
...  

Background Tissue inhibitor of metalloproteinase 1 (TIMP-1) has recently been shown to be dependent on or independent of Matrix metalloproteinases (MMPs) in its roles in tumorigenesis and progression. This appreciation has prompted various studies assessing the prognostic value of TIMP-1 in patients with gastrointestinal cancer, however, the conclusions were still inconsistent. The aim of this study was to assess the prognostic value of TIMP-1-immunohistochemistry (IHC) staining and pretreatment serum/plasma TIMP-1 level in gastrointestinal cancer survival as well as the association between TIMP-1 and clinicopathologic features. Methods The meta-analysis was registered in the International Prospective Register of Systematic Reviews (PROSPERO; Registration NO. CRD42020185407) and followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. A highly sensitive literature search was performed in electronic databases including PubMed, EMBASE and the Cochrane Library. Heterogeneity analysis was conducted using both chi-square-based Q statistics and the I2 test. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to assess the prognostic value of TIMP-1 using the fixed-effects model. Odds ratios (ORs) with 95% CIs were calculated to evaluate the associations between TIMP-1 and clinicopathological characteristics. The meta-analysis was conducted using STATA 12.0 software. Results A total of 3,958 patients from twenty-two studies were included in the meta-analysis. Elevated TIMP-1 levels were significantly associated with poor survival in gastrointestinal cancer (TIMP-1-IHC staining: HR = 2.04, 95% CI [1.59–2.61], I2 = 35.7%, PQ = 0.156; pretreatment serum/plasma TIMP-1 levels: HR = 2.02, 95% CI [1.80–2.28], I2 = 0%, PQ = 0.630). Moreover, clinicopathological parameter data analysis showed that elevated TIMP-1 levels were significantly associated with lymph node metastasis (N1/N2/N3 vs N0: OR = 2.92, 95% CI [1.95–4.38]) and higher TNM stages (III/IV vs I/II: OR = 2.73, 95% CI [1.23–6.04]). Conclusion Both TIMP-1-positive IHC staining and high serum/plasma TIMP-1 levels are poor prognostic factors for the survival of gastrointestinal cancer. In addition, TIMP-1 overexpression was correlated with more advanced clinicopathological features.


2020 ◽  
Vol 26 ◽  
pp. 107602962094259
Author(s):  
Xiaolin Zhu ◽  
Genmao Cao

Background: Endovascular therapy and intravenous thrombolysis with recombinant tissue plasminogen activator are the 2 most recommended treatments for acute ischemic stroke (AIS). Glycoprotein (GP) IIb-IIIa inhibitors are short-acting selective reversible antiplatelet agents that emerged as promising therapeutic agents for AIS about 10 years ago. Given the unclear safety profile and application coverage of GP inhibitors, we conducted this meta-analysis to explore the same. Methods: We used GP IIb-IIIa inhibitors, intracranial hemorrhage, and mortality as the key words on Medline, Web of Science, and the Embase databases. Randomized controlled trials, prospective literatures, and retrospective studies in English published between 1990 and 2020 were screened. The outcomes were relative risk (RR) of death and 90-day intracerebral hemorrhage (ICH). We pooled the results in 2 categories and conducted a subgroup analysis stratified by different drugs. The choice of the effects model depended on the value of I 2. Results: In all, 3700 patients from 20 studies were included. No GP IIb-IIIa inhibitors were found to have a remarkable influence on the ICH rate. The RR values of symptomatic ICH for abciximab and eptifibatide were 4.26 (1.89, 9.59) and 0.17 (0.04, 0.69), respectively. Both tirofiban and abciximab could decrease the mortality rate within 90 days. Age > 70 years, National Institutes of Health Stroke Scale > 15, and overall dose > 10 mg are risk factors for ICH events with tirofiban usage. Thrombectomy combined with tirofiban was safe for arterial reocclusion prevention. Conclusions: In stroke-related treatment, administration of GP IIb-IIIa inhibitors could be safe, but care should be taken regarding drug species and doses. Abciximab can increase the risk of symptomatic intracranial hemorrhage. Tirofiban and eptifibatide can be considered safe in low doses. Suitable patients should be selected using strict criteria.


2017 ◽  
Vol 45 (2) ◽  
pp. 399-406 ◽  
Author(s):  
Chengmao Zhou ◽  
Yu Zhu ◽  
Zhen Liu ◽  
Lin Ruan

Objective To investigate the effect of pretreatment with midazolam on myoclonus induced by etomidate injection. Methods A meta-analysis was performed using Review Manager software, version 5.2. Two researchers independently searched PubMed, Cochrane Library, and Embase® databases for randomized controlled trials involving patients who underwent etomidate induced general anaesthesia with or without midazolam pretreatment, published between 1990 and 2016. Outcome measures comprised overall myoclonus incidence rate and incidence rate classified by degree of myoclonus following etomidate injection. Data were assessed using a fixed effects model. Results Five studies, comprising 302 patients, were included for analysis. Overall incidence rate of etomidate injection-induced myoclonus was significantly lower in the pooled midazolam group versus controls (relative risk [RR] 0.34, 95% confidence interval [CI] 0.26, 0.44); Results subgrouped by degree of myoclonus showed significantly lower incidence in midazolam groups versus control groups for mild myoclonus (RR 0.56, 95% CI 0.39, 0.80); moderate myoclonus (RR 0.20, 95% CI 0.10, 0.41); and severe myoclonus (RR 0.12, 95% CI 0.04, 0.39). Conclusion Midazolam can effectively prevent etomidate-induced myoclonus, and alleviate the degree of etomidate-induced myoclonus.


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