Efficacy and safety of Argatroban in patients with acute ischemic stroke: a systematic review and meta-analysis
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ABSTRACT:
SUBMITTER: Cheng Y
PROVIDER: S-EPMC10909846 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:BackgroundPending results from double-blind, multicenter, parallel-group, randomized trials, the benefit and safety of the novel plasminogen activator, desmoteplase remain undetermined. The aim of this meta-analysis was to help evaluate desmoteplase's efficacy and safety.MethodsA thorough search was performed of the Cochrane Library, PubMed, and Embase from the inception of electronic data to March 2017, and double-blind, multicenter, parallel-group, randomized trials were chosen. We conducted a meta-analysis of studies investigating intravenous desmoteplase treatment of acute ischemic stroke patients 3 to 9 hours after symptom onset. Asymptomatic intracerebral hemorrhage, good clinical outcome at 90 days, and reperfusion 4 to 8 hours posttreatment were variables assessing efficacy; symptomatic intracerebral hemorrhage and death rates were measures of safety.ResultsSix trials involving 1071 patients thrombolyzed >3 hours postonset were included (600 received intravenous desmoteplase, 471 placebo). Desmoteplase was associated with increased reperfusion (odds ratio [OR] 1.57; 95% confidence interval [CI], 1.10-2.24; P = .01 vs control) and showed a tendency to increase asymptomatic intracerebral hemorrhage (OR 1.25; 95% CI, 0.97-1.62; P = .09 vs control), whereas there was no increase in symptomatic intracerebral hemorrhage and death rate with desmoteplase. However, there was no difference in the clinical response at 90 days (OR 1.14; 95% CI, 0.88-1.49; P = .31 vs control). Subgroup analysis showed that desmoteplase 90 μg/kg (OR 1.53; 95% CI, 1.07-2.21; P = .02 vs control) and 125 μg/kg (OR 4.07; 95% CI, 1.16-14.24; P = .03 vs control) were associated with an increase in reperfusion. Also, we found desmoteplase 90 μg/kg showed a tendency to increase asymptomatic intracerebral hemorrhage (OR 1.25; 95% CI, 0.95-1.63; P = .11 vs control).ConclusionIntravenous desmoteplase is associated with a favorable reperfusion efficacy and acceptable safety in ischemic stroke treatment >3 hours after symptom onset. Well-designed randomized controlled trials with larger patient cohorts and a moderate dose of drugs are needed to further evaluate the true efficacy of desmoteplase in stroke patients.Trial registrationURL: http://www.crd.york.ac.uk/PROSPERO; PROSPERO registration number: CRD42016037667).
| S-EPMC5419907 | biostudies-literature
Project description:Current treatment options for acute ischemic stroke, including intravenous thrombolysis (IVT) and mechanical thrombectomy, have undoubtedly revolutionized stroke care. The need for additional treatment options has brought into the light direct thrombin inhibitors (DTIs) and, specifically, argatroban as a promising candidate. However, there is uncertainty regarding the safety of adding argatroban to IVT, mainly due to the increased hemorrhagic risk. In this study, we performed a systematic review and meta-analysis examining the safety and efficacy of argatroban as an add-on treatment for IVT. The following databases were searched from inception until the 14th of May 2023: Pubmed/MEDLINE, ClinicalTrials.gov, the EU Clinical Trials Register, EMBASE/Scopus, and the Cochrane Library. Only randomized clinical trials (RCTs) enrolling patients with acute ischemic stroke who underwent IVT evaluating the add-on use of any DTIs were selected for the systematic review and further meta-analysis. The PRISMA guidelines were followed at all stages. Four studies with argatroban were included in the final analysis. Analysis of risk ratio and relative risk shows that the add-on therapy with argatroban seems to be effective and favors a good clinical outcome (mRS 0-2) at 90 days, similar to that of alteplase. All studies showed a low pooled incidence of symptomatic intracerebral hemorrhage (5%), parenchymal hematoma (3%), and other major bleeding (1%). Argatroban as an add-on treatment to IVT seems not to be associated with excessive bleeding risk; however, its efficacy remains unproven. According to this synopsis of the currently available evidence, it is premature to use argatroban as an add-on to IVT treatment outside the current clinical trial setting.
| S-EPMC10816854 | biostudies-literature
Project description:Background: Acute ischemic stroke (AIS) is a leading cause of death and disability worldwide. This study aimed to evaluate the efficacy and safety of anisodine hydrobromide (Ani) injection in the treatment of AIS. Methods: Randomized controlled trials (RCTs) based on Ani injection for the treatment of AIS were retrieved from both Chinese and English databases. The retrieval period was from the databases' inception to May 2023. The Cochrane Collaboration Risk of Bias Tool was used to assess the methodological quality. The outcome indicators were analyzed using RevMan 5.3 software. Results: We included the findings of 11 RCTs encompassing 1,337 patients with AIS. Our meta-analysis revealed that Ani injection supplementation significantly reduced the National Institutes of Health Stroke Scale [MD = -1.53, 95%CI = (-1.94, -1.12), p < 0.00001], modified Rankin Scale [MD = -0.89, 95%CI = (-0.97, -0.81), p < 0.00001], and the relative time to peak [SMD = -0.81, 95%CI = (-1.08, -0.55), p < 0.00001] significantly. Additionally, Ani injection significantly increased the Barthel Index [MD = 10.65, 95%CI = (4.30, 17.00), p = 0.001], relative cerebral blood volume [SMD = 0.28, 95%CI = (0.02, 0.53), p = 0.03], and clinical efficacy [RR = 1.2, 95%CI = (1.08, 1.34), p = 0.001]. No statistically significant difference in the rate of adverse events was observed between the Ani injection supplemental group and the control group. Conclusion: Based on currently published evidence, Ani injection was found to be effective and safe in improving AIS outcome. Nevertheless, limitations of the included RCTs still exist, and thus, more multi-center, large-sample, high-quality RCTs are required to further verify the efficacy and safety of Ani injection in patients with AIS. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023427591], identifier [PROSPERO 2023 CRD42023427591].
| S-EPMC10684921 | biostudies-literature
Project description:BackgroundEarly rehabilitation after acute ischemic stroke (AIS) contributes to functional recovery. However, the optimal time for starting rehabilitation remains a topic of ongoing investigation. This article aims to shed light on the safety and efficacy of very early rehabilitation (VER) initiated within 48 h of stroke onset.MethodsA systematic search in PubMed, Embase, Cochrane Library, and Web of Science databases was conducted from inception to January 20, 2024. Relevant literature on VER in patients with AIS was reviewed and the data related to favorable and adverse clinical outcomes were collected for meta-analysis. Subgroup analysis was conducted at different time points, namely at discharge and at three and 12 months. Statistical analyses were performed with the help of the Meta Package in STATA Version 15.0.ResultsA total of 14 randomized controlled trial (RCT) studies and 3,039 participants were included in the analysis. VER demonstrated a significant association with mortality [risk ratio (RR) = 1.27, 95% confidence interval (CI) (1.00, 1.61)], ability of daily living [weighted mean difference (WMD) = 6.90, 95% CI (0.22, 13.57)], and limb motor function [WMD = 5.02, 95% CI (1.63, 8.40)]. However, no significant difference was observed between the VER group and the control group in adverse events [RR = 0.89, 95% CI (0.79, 1.01)], severity of stroke [WMD = 0.52, 95% CI (-0.04, 1.08)], degree of disability [RR = 1.06, 95% CI (0.93, 1.20)], or recovery of walking [RR = 0.98, 95% CI (0.94, 1.03)] after stroke. Subgroup analysis revealed that VER reduced the risk of adverse events in the late stage (at three and 12 months) [RR = 0.86, 95% CI (0.74, 0.99)] and degree of disability at 12 months [RR = 1.28, 95% CI (1.03, 1.60)], and improved daily living ability at 3 months [WMD = 4.26, 95% CI (0.17, 8.35)], while increasing severity of stroke during hospitalization [WMD = 0.81, 95% CI (0.01, 1.61)].ConclusionVER improves activities of daily living (ADLs) and lowers the incidence of long-term complications in stroke survivors. However, premature or overly intense rehabilitation may increase mortality in patients with AIS during the acute phase. PROSPERO registration number: CRD42024508180.Systematic review registrationThis systematic review was registered with PROSPERO (https://www.crd.york.ac.uk/PROSPERO/). PROSPERO registration number: CRD42024508180.
| S-EPMC11534803 | biostudies-literature
Project description:BackgroundThe novel coronavirus disease 2019 (COVID-19) has rapidly spread worldwide and created a tremendous threat to global health. Growing evidence suggests that patients with COVID-19 have more severe acute ischemic stroke (AIS). However, the overall efficacy and safety of recanalization therapy for AIS patients infected by the SARS-CoV-2 virus is unknown.MethodsThe PRISMA guideline 2020 was followed. Two independent investigators systematically searched databases and ClinicalTrials.gov to identify relevant studies published up to 31 March 2022. AIS patients who received any recanalization treatments were categorized into those with COVID-19 and those without COVID-19. The main efficacy outcomes were patients' functional independence on discharge and successful recanalization, and the safety outcomes were in-hospital mortality and symptomatic intracranial hemorrhage. Subgroup analyses were implemented to assess the influence of admission National Institutes of Health Stroke Scale and different recanalization treatments on the outcomes. STATA software 12.0 was used for the statistical analysis.ResultsThis systematic review and meta-analysis identified 10 studies with 7,042 patients, including 596 COVID-19 positive patients and 6,446 COVID-19 negative patients. Of the total patients, 2,414 received intravenous thrombolysis while 4,628 underwent endovascular thrombectomy. COVID-19 positive patients had significantly lower rates of functional independence at discharge [odds ratio (OR) 0.30, 95% confidence interval (CI) 0.15 to 0.59, P = 0.001], lower rates of successful recanalization (OR 0.40, 95% CI 0.24 to 0.68, P = 0.001), longer length of hospital stay (weighted mean difference 5.09, 95% CI 1.25 to 8.94, P = 0.009) and higher mortality rates (OR 3.38, 95% CI 2.43 to 4.70, P < 0.0001). Patients with COVID-19 had a higher risk of symptomatic intracranial hemorrhage than the control group, although the difference did not reach statistical significance (OR 2.34, 95% CI 0.99 to 5.54, P = 0.053).ConclusionsCompared with COVID-19 negative AIS patients who received recanalization treatments, COVID-19 positive patients turned out to have poorer outcomes. Particular attention needs to be paid to the treatments for these COVID-19 patients to decrease mortality and morbidity. Long-term follow-up is necessary to evaluate the recanalization treatments for AIS patients with COVID-19.Systematic review registrationhttps://inplasy.com/inplasy-2022-4-0022/, identifier: INPLASY202240022.
| S-EPMC9468325 | biostudies-literature
Project description:Background: Xingnaojing injection (XNJ) is derived from a traditional Chinese prescription named Angong Niuhuang pill. As an adjuvant treatment widely used in acute ischemic stroke (AIS), XNJ has proven to be effective with certain clinical evidence. The aim of this study is to collect the latest evidence and evaluate efficacy and safety of XNJ for emergency treatment of AIS. Methods: We searched seven literature databases and two clinical trial registries from their inception to November 14, 2021 for randomized controlled trials (RCTs) examining the efficacy of XNJ for AIS. Two reviewers independently selected relevant trials, extracted data, and assessed the risk of bias. We pooled data into a meta-analysis using RevMan 5.4 software. Results: Thirty-eight RCTs were included in this review, with a total of 3,677 participants. XNJ plus conventional treatments (CTs) showed a significant advantage, compared with CTs alone, in improving functional independence at 14 days (RR = 1.70, 95% CI = 1.03 to 2.81, p = 0.04), neurological function (MD NIHSS < 6h = -3.81, 95% CI = -5.25 to -2.38, p < 0.00001; MD NIHSS < 24h = -3.75, 95% CI = -4.92 to -2.59, p < 0.00001; MD NIHSS < 72h = -3.74, 95% CI = -5.48 to -2.00, p < 0.0001; MD NIHSS < 14d = -1.97, 95% CI = -3.25 to -0.69, p = 0.003), and activities of daily living on the Barthel index (MD BI-14day = 9.97, 95% CI = 9.29 to 10.65, p < 0.00001; MD BI-30day = 10.04, 95% CI = 5.82, to 14.26, p < 0.00001). In addition, the results showed that XNJ plus CTs was superior to CTs alone in reducing IL-6, TNF-α, hs-CRP, and MMP-9. Regarding safety of XNJ, the incidence of adverse reactions in the XNJ group was lower than that in the control group (RR = 0.57, 95% CI = 0.38 to 0.87, p = 0.009). The certainty of evidence was evaluated as low or very low for all. Conclusion: XNJ appears to be effective and safe for emergency treatment of AIS. The first 72 h after the onset of stroke, in particular the first 6 hours, may be the optimum initiation time. However, further high-quality RCTs are warranted to determine an appropriate initiation time. Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=233211], identifier [CRD42021233211].
| S-EPMC8987164 | biostudies-literature
Project description:BackgroundVinpocetine as a neuroprotective agent is effective in acute ischemic stroke in some randomized controlled trials (RCTs). Since the last systematic review has been published in 2008, which didn't find conclusive evidence favoring its use, two more RCTs have also been completed.MethodsRelevant electronic databases were searched with a suitable combination of Medical Subject Headings terms to detect publications describing RCTs exploring the safety and efficacy of vinpocetine in patients with acute ischemic stroke. The risk of bias was determined by using the Cochrane Collaboration's tool for assessing the risk of bias in RCTs after full-text review and relevant data extraction. Higgins and Thompson's I2 method was used to assess heterogeneity in studies. The presence of publication bias was assessed by Egger's test. We used a random effect model when I2 was more than 50% and a fixed-effect model for other parameters.ResultsFour placebo-controlled RCTs enrolling a total of 601 and 236 patients in vinpocetine and placebo groups, respectively, were included. The number of patients with death or significant disability was lower in the vinpocetine group than that in the placebo group at both 1 and 3 months (relative risk 0.80, 95% confidence interval [CI] 0.65-0.99 and relative risk 0.67, CI 0.48-0.92, p = 0.04 and 0.02, respectively). The degree of disability in participants at 1 month and 3 months was also lower in vinpocetine group than that in the placebo group (standardized mean difference (SMD) 0.49, 95% CI 0.03-0.95 and SMD 1.22, CI 0.23-2.24, p = 0.001 and 0.04, respectively). Change in mini-mental state examination score compared with baseline at trial enrolment was also better in the vinpocetine group than in the placebo group (pooled weighted mean difference 0.92, 95% CI 0.02-1.82, p = 0.04).ConclusionsVinpocetine has some promising efficacy in patients with ischemic stroke when used in the acute stage in reducing the disability, but presently there is not enough evidence to suggest that it also reduces case fatality. More double-blind, placebo-controlled RCTs of adequate sample size are needed before making recommendations for the routine administration of vinpocetine for all patients with acute ischemic stroke.
| S-EPMC9053840 | biostudies-literature
Project description:BackgroundEndovascular thrombectomy (EVT) is an effective therapy in acute ischemic stroke (AIS) with large vessel occlusion, especially for those who are unsuitable for intravenous thrombolysis. However, the safety and efficacy of EVT in AIS patients who receiving oral anticoagulants (OACs) is unclear, especially for the risk of symptomatic intracranial hemorrhage (sICH). METHODS: Database of PubMed, Embase, and Cochrane Library were searched from Jan 1, 2000, through the final search date of Jun 2, 2021. Eligible studies for enrollment required outcomes reported for events of sICH, mortality, functional status, and successful reperfusion. Meta-analysis was conducted to compare the outcomes difference after EVT between AIS patients with or without OACs use. The primary safety outcome was sICH after EVT, and the primary efficacy outcome was functional status at 3 months. RESULTS: One thousand nine hundred forty studies were screened for eligibility and 15 of them were included in the meta-analysis. Compared the OACs group to control arm, vitamin K antagonists (VKAs) was associated with higher risk of sICH (OR 1.49, 95% CI 1.10-2.02) and mortality (OR 1.67, 95% CI 1.35-2.06). Poor functional outcomes were noted both in the VKAs and direct oral anticoagulants (DOACs) groups (OR 0.62, 95% CI 0.54-0.71 and OR 0.61, 95% CI 0.53-0.71, respectively). No differences in successful reperfusion were observed.ConclusionsComparing with DOACs, VKAs use was associated with a higher risk of sICH and mortality after EVT. Patients who did not receive OACs exhibited more favorable outcomes. The successful reperfusion did not differ between groups. However, results for mortality and functional outcomes have to be interpreted with caution since they are based on non-randomized data and unadjusted proportions.
| S-EPMC9210791 | biostudies-literature
Project description:The efficacy and safety of intravenous thrombolysis (IVT) for acute ischemic stroke (AIS) in cancer patients remained uncertain due to low level evidence in the latest guideline for AIS. The aim of this study was to assess the efficacy and safety of IVT in cancer patients with stronger evidence. We searched Medline, Embase, CENTRAL and ClinicalTrials.gov until April 2020 for studies reporting outcomes of functional independence, hemorrhagic transformation (HT), symptomatic intracranial hemorrhage (SICH), major bleeding (MB), in-hospital mortality or 3-month mortality after IVT for AIS in cancer patients. For each outcome, the odds ratio between cancer and non-cancer patients, the risk difference between gastrointestinal and other malignancy, and the proportion in cancer patients were calculated. The meta-analysis showed no significant difference between cancer and non-cancer patients in favorable outcome, HT, SICH, MB, in-hospital mortality and 3-month mortality. Furthermore, there's no significant difference between patients with gastrointestinal and other malignancy in favorable outcome, HT, SICH, MB and 3-month mortality. In race-based subgroup analysis, Asians implied greater likelihood of HT and SICH than non-Asians. Therefore, the study confirmed and strengthened the validity of the guideline with stronger evidence that cancer shouldn't be an exclusion criterion of IVT. Inconsistent with the guideline, gastrointestinal malignancy may not remain an absolute contraindication of IVT while Asians implied increased HT and SICH, which needed further exploration.
| S-EPMC7476124 | biostudies-literature
Project description:ObjectivePrevious studies suggest the benefit of dual antiplatelet therapy (DAPT) for acute ischemic stroke with large artery atherosclerosis (LAA) etiology, but there is no study about the effect of DAPT plus anticoagulant in this population.MethodsA prospective single arm trial was performed to determine the effect of DAPT combined with argatroban on acute mild to moderate ischemic stroke patients with LAA, which was compared with historical populations. The main outcome was the proportion of early neurological deterioration (END). The secondary outcomes included scores of 0 to 1 and 0 to 2 on the modified Rankin Scale (mRS) at 90 days, and changes in National Institutes of Health Stroke Scale (NIHSS) from baseline to day 7 after admission. The safety outcomes included intracranial hemorrhage at 7 days, organ hemorrhage, and all-cause mortality at 90 days.ResultsA total of 120 patients with argatroban plus DAPT were prospectively enrolled and 529 patients with only DAPT were retrospectively collected. There was no significant difference in baseline characteristics between groups. Compared with control group, combined treatment group had lower proportion of END (4.2% vs. 10.0%, adjusted p = .046), more reduction in NIHSS score from the baseline to day 7 after admission (1.06 ± 2.03 vs. 0.39 ± 1.97, adjusted p = .003), and higher proportion of mRS (0-2) at 90 days (87.5% vs. 79.2%, adjusted p = .048). No intracranial hemorrhage was found between groups.ConclusionsThis is the first report that short-term argatroban combined with DAPT seems to be safe and may effectively prevent END and improve neurological prognosis for acute mild to moderate ischemic stroke patients with LAA; however, interpretation of the conclusion required caution due to nonrandomized controlled trial with medium sample size.
| S-EPMC9304821 | biostudies-literature