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Tongqiao Huoxue Decoction for the treatment of acute ischemic stroke: A Systematic Review and meta-analysis.
Zhou, X, Shao, T, Xie, X, Ding, M, Jiang, X, Su, P, Jin, Z
Journal of ethnopharmacology. 2022;:114693
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE The aim of this study was to evaluate the efficacy and safety of Tongqiao Huoxue Decoction (TQHXT) in the treatment of acute ischemic stroke (AIS); Study Design: A total of 17 randomized controlled trials, involving 1489 AIS patients, were included for data analyses. MATERIALS AND METHODS All randomized controlled trials (RCTs) of TQHXT in the treatment of acute ischemic stroke before September 2020 were retrieved from seven electronic databases, including PubMed, Web of Science, Central, CNKI, CBM, Wanfang, and VIP. Data were analyzed by RevMan 5.3 software, and quality was evaluated by GRADEpro; Results: Results showed that, while TQHXT demonstrated undeniable positive effects in clinical effective rate, neurological deficit scores, activities of daily living (ADL) scores, and hemorheology (including HCT; fibrinogen; plasma viscosity and platelet adherence rate), adverse events (AE) require further study; and Conclusions: This study provides evidence that TQHXT is an effective treatment for acute ischemic stroke. However, due to the limited quality of the included studies, the above conclusion needs to be further verified by stricter randomized controlled, double-blind, large-sample, high-quality trials.
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Ginkgol Biloba extract as an adjunctive treatment for ischemic stroke: A systematic review and meta-analysis of randomized clinical trials.
Ji, H, Zhou, X, Wei, W, Wu, W, Yao, S
Medicine. 2020;(2):e18568
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Abstract
OBJECTIVE Ginkgo biloba extract (GBE) is widely used as an adjunctive treatment for ischemic stroke. This meta-analysis aimed to evaluate the effectiveness and safety of GBE specifically for long-term users at the convalescence stage of ischemic stroke. METHODS MEDLINE, Cochrane Central Register of Controlled Trials, Embase Database, WHO Clinical Trials Registration Platform, Chinese National Knowledge Infrastructure, Wanfang Database, and Chinese Scientific Journal Database were searched from inception to 20 September 2018. Risk ratio (RR) and mean difference (MD) with a 95% confidence interval (CI) were used as effect estimates using RevMan software (5.3; Review Manager [RevMan], Nordic Cochrane Centre, Copenhagen, Denmark). A meta-analysis was performed where data were available. A trial sequential analysis was used to control random errors for recurrence rate and the GRADE (grading of recommendations, assessment, development, and evaluations) approach was used to assess the quality of the body of evidence. The meta-analysis design was registered on PROSPERO (CRD42018110211, http://www.crd.york.ac.uk/PROSPERO). RESULTS We identified 15 randomized clinical trials involving 1829 participants. The majority of the included trials were of high risk of bias in methodological quality. For acute ischemic stroke, adding GBE to conventional therapy led to higher Barthel index scores (MD: 5.72; 95% CI: 3.11-8.33) and lower neurological function deficit scores (MD: -1.39; 95% CI: -2.15 to -0.62). For patients in their convalescence (or sequelae) stage of ischemic stroke, GBE was superior in improving dependence (MD: 7.17; 95% CI: 5.96-8.38) and neurological function deficit scores (MD: -1.15; 95% CI: -1.76 to -0.53) compared with placebo or conventional therapy, but there was no difference in vascular events (RR: 0.70; 95% CI: 0.44-1.14), recurrence rate (RR: 0.57; 95% CI: 0.26-1.25; trial sequential analysis: conclusive) and mortality (RR: 1.07; 95% CI: 0.41-2.81). CONCLUSIONS GBE appears to improve neurological function and dependence compared with conventional therapy for ischemic stroke at different stages and appears generally safe for clinical application. The lack of improvement in recurrence rate was confirmed by trial sequential analysis. Due to the generally weak evidence, further large, rigorous trials are warranted.
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Carotid Plaque Positron Emission Tomography Imaging and Cerebral Ischemic Disease.
Chaker, S, Al-Dasuqi, K, Baradaran, H, Demetres, M, Delgado, D, Nehmeh, S, Osborne, JR, Christos, PJ, Kamel, H, Gupta, A
Stroke. 2019;(8):2072-2079
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Background and Purpose- The clinical utility of positron emission tomography (PET) imaging in evaluating carotid artery plaque vulnerability remains unclear. Two tracers of recent interest for carotid plaque imaging are 18F-fluorodeoxyglucose (18F-FDG) and 18F-sodium fluoride (18F-NaF). We performed a systematic review and meta-analysis evaluating the association between carotid artery 18F-FDG or 18F-NaF uptake and recent or future cerebral ischemic events. Methods- A systematic review of Ovid MEDLINE, Ovid EMBASE, and the Cochrane library was conducted from inception to December 2017 for articles evaluating PET tracer uptake in recently symptomatic versus asymptomatic carotid arteries, and articles evaluating carotid uptake in relation to future ischemic events. Cerebral ischemic events were defined as ipsilateral strokes, transient ischemic attacks, or amaurosis fugax. We quantitatively pooled studies by a random-effects model when 3 or more studies were amenable for analysis. We assessed the standardized mean difference between tracer uptake in the symptomatic versus asymptomatic carotid artery using Cohen's d metric. Results- After screening 4144 unique articles, 13 prospective cohort studies assessing carotid artery 18F-FDG uptake in patients with recent cerebral ischemia were eligible for review. Eleven cohorts of 290 subjects scanned with 18F-FDG were eligible for meta-analysis. We found that carotid arteries ipsilateral to recent ischemic events had significantly higher 18F-FDG uptake than asymptomatic arteries (Cohen's d =0.492; CI=0.130-0.855; P=0.008) as well as significant heterogeneity (Cochran's Q =31.5; P=0.0005; I2=68.3%). Meta-regression was not performed due to the limited number of studies in the analysis. Only 2 studies investigating 18F-NaF PET imaging, and another 2 articles investigating ischemic event recurrence were found. Conclusions- Recent ipsilateral cerebral ischemia may be associated with increased carotid 18F-FDG uptake on PET imaging regardless of degree of carotid stenosis, although significant heterogeneity was found, and these results should be interpreted with caution. Emerging evidence suggests a similar association may be present with 18F-NaF plaque uptake. More studies are warranted to provide definitive conclusions on the utility of 18F-FDG or 18F-NaF in carotid plaque evaluation before investigating carotid PET as a diagnostic tool for cerebral ischemic events.
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Adherence to the Mediterranean diet and risk of stroke and stroke subtypes.
Chen, GC, Neelakantan, N, Martín-Calvo, N, Koh, WP, Yuan, JM, Bonaccio, M, Iacoviello, L, Martínez-González, MA, Qin, LQ, van Dam, RM
European journal of epidemiology. 2019;(4):337-349
Abstract
Several meta-analyses including a small number of cohorts showed inverse associations between the Mediterranean Diet (MedDiet) and risk of stroke. However, it remains unclear whether such a relation varies by region of the study population or by major subtypes of stroke. We searched PubMed and EMBASE databases for relevant studies and we further included unpublished results from the Singapore Chinese Health Study (N = 57,078) and the Seguimiento Universidad de Navarra (SUN) study (N = 12,670). We used a random-effects model to calculate summary relative risk (RR) with 95% confidence intervals (CI) of stroke for each 4-point increment of the MedDiet score, roughly corresponding to the difference between extreme quintiles of the MedDiet score among participants of the included studies. The final analyses included 20 prospective cohort studies involving 682,149 participants and 16,739 stroke cases. The summary RRs for each 4-point increment of the MedDiet score were 0.84 (95% CI 0.81-0.88; I2 = 11.5%) for all combined, 0.76 (95% CI 0.65-0.89) for studies in Mediterranean populations and 0.86 (95% CI 0.83-0.89) for those in non-Mediterranean populations. Lower risk of stroke associated with higher MedDiet score also was observed in the analyses stratified by study population and methodological characteristics including study risk of bias, version of the MedDiet index, and definition of moderate alcohol consumption. The MedDiet was similarly associated with lower risk of ischemic stroke (RR 0.86, 95% CI 0.81-0.91; nine studies) and hemorrhagic stroke (RR 0.83, 95% CI 0.74-0.93; eight studies). Our meta-analysis suggests that adhering to the Mediterranean diet was associated with lower risk of stroke in both Mediterranean and non-Mediterranean populations, and for both ischemic stroke and hemorrhagic stroke risk.
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Direct Oral Anticoagulants Versus Vitamin K Antagonists in Real-life Patients With Atrial Fibrillation. A Systematic Review and Meta-analysis.
Escobar, C, Martí-Almor, J, Pérez Cabeza, A, Martínez-Zapata, MJ
Revista espanola de cardiologia (English ed.). 2019;(4):305-316
Abstract
INTRODUCTION AND OBJECTIVES To assess the effectiveness of direct oral anticoagulants vs vitamin K antagonists in real-life patients with atrial fibrillation. METHODS A systematic review was performed according to Cochrane methodological standards. The results were reported according to the PRISMA statement. The ROBINS-I tool was used to assess risk of bias. RESULTS A total of 27 different studies publishing data in 30 publications were included. In the studies with a follow-up up to 1 year, apixaban (HR, 0.93; 95%CI, 0.71-1.20) and dabigatran (HR, 0.95; 95%CI, 0.80-1.13) did not significantly reduce the risk of ischemic stroke vs warfarin, whereas rivaroxaban significantly reduced this risk (HR, 0.83; 95%CI, 0.73-0.94). Apixaban (HR, 0.66; 95%CI, 0.55-0.80) and dabigatran (HR, 0.83; 95%CI, 0.70-0.97) significantly reduced the major bleeding risk vs warfarin, but not rivaroxaban (HR, 1.02; 95%CI, 0.95-1.10), although with a high statistical heterogeneity among studies. Apixaban (HR, 0.56; 95%CI, 0.42-0.73), dabigatran (HR, 0.45; 95%CI, 0.39-0.51), and rivaroxaban (HR, 0.66; 95%CI, 0.49-0.88) significantly reduced the risk of intracranial bleeding vs warfarin. Reduced doses of direct oral anticoagulants were associated with a slightly better safety profile, but with a marked reduction in stroke prevention effectiveness. CONCLUSIONS Data from this meta-analysis suggest that, vs warfarin, the stroke prevention effectiveness and bleeding risk of direct oral anticoagulants may differ in real-life patients with atrial fibrillation.
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A Systematic Review of Neuroprotective Efficacy and Safety of DL-3-N-Butylphthalide in Ischemic Stroke.
Xu, ZQ, Zhou, Y, Shao, BZ, Zhang, JJ, Liu, C
The American journal of Chinese medicine. 2019;(3):507-525
Abstract
DL-3-n-butylphthalide (NBP) is widely used as a neuroprotective drug for ischemic stroke in China. There is, however, no established evidence on its efficacy and safety for patients with ischemic stroke. We, therefore, conducted a systematic review and meta-analysis. Major databases were searched to identify randomized controlled trials that assessed the efficacy and safety of NBP on ischemic stroke, reporting outcomes among patients treated with NBP alone or combined with standard anti-ischemic stroke drugs vs. standard anti-ischemic stroke drugs. Continuous data were validated, extracted and synthesized of standardized mean differences (SMDs) by random effects models, while dichotomous data were validated, extracted and synthesized of relative risk (RR) by random effects models. Twelve randomized controlled trials involving 1160 patients were identified. Results suggested that NBP monotherapy is not superior to standard anti-ischemic stroke drugs based on the Barthel Index (SMD, 0.25; 95% CI - 0.14 to 0.63; P=0.21 ) and the National Institutes of Health Stroke Scale (SMD, 0.73; 95% CI - 0.14 to 1.59; P=0.10 ). In contrast, the combination of NBP and standard anti-ischemic stroke drugs appears to be superior to standard drugs alone, again based on both the Barthel index (SMD, 1.65; 95% CI 1.25 to 2.04; P<0.01 ) and National Institutes of Health Stroke Scale (SMD, 1.40; 95% CI 0.72 to 2.09; P<0.01 ). However, the use of NBP may cause adverse event on the function of the liver (RR, 3.55; 95% CI 1.19 to 10.56; P<0.05 ). The combination use of NBP and standard anti-ischemic stroke drugs is more effective than standard drugs. However, more attention should be payed to the adverse effects on liver function. Our findings provided an established evidence of NBP as a neuroprotective drug, which may improve the current guideline for treatment of ischemic stroke.
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Intravenous Magnesium Sulfate in Acute Stroke.
Avgerinos, KI, Chatzisotiriou, A, Haidich, AB, Tsapas, A, Lioutas, VA
Stroke. 2019;(4):931-938
Abstract
Background and Purpose- Acute stroke treatment is challenging, and stroke remains a major cause of death and disability. The purpose of this meta-analysis is to investigate the effects of postacute stroke intravenous administration of the neuroprotectant magnesium sulfate (MgSO4) on global outcome, functional outcome, and mortality 90 days poststroke (ischemic and nonischemic). Methods- We searched in Pubmed, Science Direct, CENTRAL, and ClinicalTrials.gov, up to November 11, 2017, and we conducted a systematic review and meta-analysis of randomized controlled trials. We synthesized results by using random-effects model, weighted mean differences, standardized mean differences, and odds ratios. Results- Seven randomized controlled trials (4347 patients) met our criteria. Compared with placebo, treatment did not improve functional outcome defined as Barthel Index >60 (odds ratio =1.05; 95% CI, 0.92-1.19) and >95 (odds ratio =0.95; 95% CI, 0.76-1.20), 90 days poststroke. It also did not improve global outcome measured with modified Rankin Scale (standardized mean difference =-0.01; 95% CI, -0.12 to 0.10), 90 days poststroke. In an additional subgroup meta-analysis that exclusively included ischemic stroke patients, intravenous MgSO4 resulted in lower modified Rankin Scale score (improved global outcome; weighted mean difference =-0.96; 95% CI, -1.34 to -0.58; I2=0%], 90 days poststroke. Finally, mortality stayed unaltered (odds ratio =1.10; 95% CI, 0.94-1.29). Conclusions- The findings of our meta-analysis showed that intravenous MgSO4 generally did not improve global/functional outcomes and mortality at 90 days after stroke (combined ischemic stroke and nonischemic stroke). The finding of favorable neurological outcome, selectively in ischemic stroke patients, should be viewed with extreme caution given the limited number of patients included in this subgroup meta-analysis.
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Effect of general anaesthesia on functional outcome in patients with anterior circulation ischaemic stroke having endovascular thrombectomy versus standard care: a meta-analysis of individual patient data.
Campbell, BCV, van Zwam, WH, Goyal, M, Menon, BK, Dippel, DWJ, Demchuk, AM, Bracard, S, White, P, Dávalos, A, Majoie, CBLM, et al
The Lancet. Neurology. 2018;(1):47-53
Abstract
BACKGROUND General anaesthesia (GA) during endovascular thrombectomy has been associated with worse patient outcomes in observational studies compared with patients treated without GA. We assessed functional outcome in ischaemic stroke patients with large vessel anterior circulation occlusion undergoing endovascular thrombectomy under GA, versus thrombectomy not under GA (with or without sedation) versus standard care (ie, no thrombectomy), stratified by the use of GA versus standard care. METHODS For this meta-analysis, patient-level data were pooled from all patients included in randomised trials in PuMed published between Jan 1, 2010, and May 31, 2017, that compared endovascular thrombectomy predominantly done with stent retrievers with standard care in anterior circulation ischaemic stroke patients (HERMES Collaboration). The primary outcome was functional outcome assessed by ordinal analysis of the modified Rankin scale (mRS) at 90 days in the GA and non-GA subgroups of patients treated with endovascular therapy versus those patients treated with standard care, adjusted for baseline prognostic variables. To account for between-trial variance we used mixed-effects modelling with a random effect for trials incorporated in all models. Bias was assessed using the Cochrane method. The meta-analysis was prospectively designed, but not registered. FINDINGS Seven trials were identified by our search; of 1764 patients included in these trials, 871 were allocated to endovascular thrombectomy and 893 were assigned standard care. After exclusion of 74 patients (72 did not undergo the procedure and two had missing data on anaesthetic strategy), 236 (30%) of 797 patients who had endovascular procedures were treated under GA. At baseline, patients receiving GA were younger and had a shorter delay between stroke onset and randomisation but they had similar pre-treatment clinical severity compared with patients who did not have GA. Endovascular thrombectomy improved functional outcome at 3 months both in patients who had GA (adjusted common odds ratio (cOR) 1·52, 95% CI 1·09-2·11, p=0·014) and in those who did not have GA (adjusted cOR 2·33, 95% CI 1·75-3·10, p<0·0001) versus standard care. However, outcomes were significantly better for patients who did not receive GA versus those who received GA (covariate-adjusted cOR 1·53, 95% CI 1·14-2·04, p=0·0044). The risk of bias and variability between studies was assessed to be low. INTERPRETATION Worse outcomes after endovascular thrombectomy were associated with GA, after adjustment for baseline prognostic variables. These data support avoidance of GA whenever possible. The procedure did, however, remain effective versus standard care in patients treated under GA, indicating that treatment should not be withheld in those who require anaesthesia for medical reasons. FUNDING Medtronic.
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Adjunctive herbal medicine treatment for patients with acute ischemic stroke: A systematic review and meta-analysis.
Han, CH, Kim, M, Cho, SY, Jung, WS, Moon, SK, Park, JM, Ko, CN, Cho, KH, Kwon, S
Complementary therapies in clinical practice. 2018;:124-137
Abstract
BACKGROUND AND PURPOSE In the East-Asian countries, the combined treatment of Western medicine and herbal medicine has been widely administered. The purpose of this study was to evaluate the efficacy and safety of herbal medicine in the treatment of acute ischemic stroke. METHODS We searched the PubMed, Cochrane Central Register of Controlled Trials, EMBASE, and CNKI up to January 2017. Randomized Controlled Trials evaluating the effect of adjunctive herbal medicine on acute ischemic stroke were included. RESULTS A total of 80 studies (8057 patients) were collected. The overall methodological quality was low. In the herbal group, meta-analysis indicated a statistically significant improvement in the neurologic deficits and activity of daily living compared with the non-herbal group. Furthermore, herbal treatments were relatively safe. CONCLUSION The treatment can induce neurological improvements without side effects. However, concrete conclusions cannot be made due to the methodological problems of the included studies.
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Safety and efficacy of Cerebrolysin in early post-stroke recovery: a meta-analysis of nine randomized clinical trials.
Bornstein, NM, Guekht, A, Vester, J, Heiss, WD, Gusev, E, Hömberg, V, Rahlfs, VW, Bajenaru, O, Popescu, BO, Muresanu, D
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2018;(4):629-640
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This meta-analysis combines the results of nine ischemic stroke trials, assessing efficacy of Cerebrolysin on global neurological improvement during early post-stroke period. Cerebrolysin is a parenterally administered neuropeptide preparation approved for treatment of stroke. All included studies had a prospective, randomized, double-blind, placebo-controlled design. The patients were treated with 30-50 ml Cerebrolysin once daily for 10-21 days, with treatment initiation within 72 h after onset of ischemic stroke. For five studies, original analysis data were available for meta-analysis (individual patient data analysis); for four studies, aggregate data were used. The combination by meta-analytic procedures was pre-planned and the methods of synthesis were pre-defined under blinded conditions. Search deadline for the present meta-analysis was December 31, 2016. The nonparametric Mann-Whitney (MW) effect size for National Institutes of Health Stroke Scale (NIHSS) on day 30 (or 21), combining the results of nine randomized, controlled trials by means of the robust Wei-Lachin pooling procedure (maximin-efficient robust test), indicated superiority of Cerebrolysin as compared with placebo (MW 0.60, P < 0.0001, N = 1879). The combined number needed to treat for clinically relevant changes in early NIHSS was 7.7 (95% CI 5.2 to 15.0). The additional full-scale ordinal analysis of modified Rankin Scale at day 90 in moderate to severe patients resulted in MW 0.61 with statistical significance in favor of Cerebrolysin (95% CI 0.52 to 0.69, P = 0.0118, N = 314). Safety aspects were comparable to placebo. Our meta-analysis confirms previous evidence that Cerebrolysin has a beneficial effect on early global neurological deficits in patients with acute ischemic stroke.