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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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Fasting blood glucose and risk of Stroke: A Dose-Response meta-analysis.
Shi, H, Ge, Y, Wang, H, Zhang, Y, Teng, W, Tian, L
Clinical nutrition (Edinburgh, Scotland). 2021;(5):3296-3304
Abstract
BACKGROUND & PURPOSE A growing number of studies have shown that fasting blood glucose is related to the risk of stroke, however, the dose-response association between fasting blood glucose and the risk of stroke is still unclear. Accordingly, we conducted a dose-response meta-analysis to evaluate the relationship between fasting blood glucose and the risk of stroke by summarizing cohort studies. METHODS PubMed and Embase databases were searched for related studies (until October 2020). Cohort studies examining the influence of fasting blood glucose on stroke risk were summarized. A dose-response relationship was determined using a random-effect model. RESULTS Eighteen cohort studies involving 2,555,666 participants were included. The pooled relative risk for the high-versus-low categories was 1.79 (95% CI: 1.68-1.91) in all people, and 1.16 (95% CI: 1.11-1.21) in non-diabetic people. In addition, there was a non-linear relationship between fasting blood glucose and stroke risk. The incidence of stroke was reduced to its lowest point when fasting blood glucose level was 70-100 mg/dL. CONCLUSION Fasting blood glucose was positively related to stroke risk, with a non-linear dose-response relationship.
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The Influence of Val66Met Polymorphism in Brain-Derived Neurotrophic Factor on Stroke Recovery Outcome: A Systematic Review and Meta-analysis.
Liu, X, Fang, JC, Zhi, XY, Yan, QY, Zhu, H, Xie, J
Neurorehabilitation and neural repair. 2021;(6):550-560
Abstract
Background and purpose. A single nucleotide polymorphism at nucleotide 196 (G/A) in the human brain-derived neurotrophic factor (BDNF) gene produces an amino acid substitution (valine to methionine) at codon 66(Val66Met). It is unclear whether carriers of this substitution may have worse functional outcomes after stroke. We aimed to explore the distribution of Val66Met polymorphism and evaluate the effect of different genotypes on stroke functional recovery. Methods. Several databases were searched using the keywords BDNF or brain-derived neurotrophic factor, codon66, G196A, rs6265, or Val66Met, and stroke. Results. A total of 25 articles were relevant to estimate the distribution of alleles; 5 reports were applied in the meta-analysis to assess genetic differences on recovery outcomes. The genetic model analysis showed that the recessive model should be used; we combined data for AA versus GA+GG (GG-Val/Val, GA-Val/Met, AA-Met/Met). The results showed that stroke patients with AA might have worse recovery outcomes than those with GA+GG (odds ratio = 1.90; 95% CI: 1.17-3.10; P = .010; I2 = 69.2%). Overall, the A allele may be more common in Asian patients (48.6%; 95% CI: 45.8%-51.4%, I2 = 54.2%) than Caucasian patients (29.8%; 95% CI: 7.5%-52.1%; I2 = 99.1%). However, in Caucasian patients, the frequency of the A allele in Iranians (87.9%; 95% CI: 83.4%-92.3%) was quite higher than that in other Caucasians (18.7%; 95% CI: 16.6%-20.9%; I2 = 0.00%). Conclusion. Val66Met AA carriers may have worse rehabilitation outcomes than GA+GG carriers. Further studies are needed to determine the effect of Val66Met polymorphism on stroke recovery and to evaluate this relationship with ethnicity, sex, age, stroke type, observe duration, stroke severity, injury location, and therapies.
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Gliflozins for the prevention of stroke in diabetes and cardiorenal diseases: A meta-analysis of cardiovascular outcome trials.
Zhao, LM, Huang, JN, Qiu, M, Ding, LL, Zhan, ZL, Ning, J
Medicine. 2021;(39):e27362
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Abstract
BACKGROUND Individual randomized trials are not powered to assess the relationship between use of sodium-glucose transporter 2 inhibitors and risk of stroke. We sought to explore this issue by a meta-analysis incorporating relevant trials including several latest trials. METHODS Cardiovascular outcome trials of gliflozins were included. Primary outcome was stroke, while secondary outcome was major adverse cardiovascular events (MACE), which was a composite of stroke, myocardial infarction, or cardiovascular death. Meta-analysis was conducted stratified by with/without chronic kidney disease (CKD), with/without heart failure (HF), and with/without atherosclerotic cardiovascular disease (ASCVD), and stratified by different gliflozins. RESULTS We included 9 trials in this meta-analysis. Compared with placebo, gliflozins significantly lowered stroke (hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.55-0.84) and MACE (HR 0.77, 95% CI 0.69-0.86) in type 2 diabetes (T2D) patients with CKD, but did not significantly affect stroke (HR 1.00, 95% CI 0.86-1.16) and MACE (HR 0.94, 95% CI 0.86-1.02) in T2D patients without CKD. Gliflozins had no significant effects on the stroke risk (HR 0.94, 95% CI 0.82-1.07) in T2D patients regardless of HF status (Psubgroup = .684) and ASCVD status (Psubgroup = .915), but significantly lowered MACE (HR 0.89, 95% CI 0.83-0.96) in T2D patients regardless of HF status (Psubgroup = .428) and ASCVD status (Psubgroup = .423). Canagliflozin (HR 0.84, 95% CI 0.69-1.01) showed the trend of a reduction in the stroke risk versus placebo, and sotagliflozin (HR 0.73, 95% CI 0.54-0.98) significantly lowered the stroke risk; whereas the other 3 gliflozins did not significantly affect that risk. Ertugliflozin (HR 0.97, 95% CI 0.85-1.11) had no significant effects on the MACE risk, whereas the other 4 gliflozins significantly lowered that risk. CONCLUSIONS Gliflozins, especially canagliflozin and sotagliflozin, should be recommended in T2D patients with CKD to prevent stroke. Most gliflozins lower the risk of MACE in T2D patients regardless of HF status and ASCVD status, whereas ertugliflozin is not observed to lower that risk.
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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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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 Intima-Media Thickness Progression as Surrogate Marker for Cardiovascular Risk: Meta-Analysis of 119 Clinical Trials Involving 100 667 Patients.
Willeit, P, Tschiderer, L, Allara, E, Reuber, K, Seekircher, L, Gao, L, Liao, X, Lonn, E, Gerstein, HC, Yusuf, S, et al
Circulation. 2020;(7):621-642
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Abstract
BACKGROUND To quantify the association between effects of interventions on carotid intima-media thickness (cIMT) progression and their effects on cardiovascular disease (CVD) risk. METHODS We systematically collated data from randomized, controlled trials. cIMT was assessed as the mean value at the common-carotid-artery; if unavailable, the maximum value at the common-carotid-artery or other cIMT measures were used. The primary outcome was a combined CVD end point defined as myocardial infarction, stroke, revascularization procedures, or fatal CVD. We estimated intervention effects on cIMT progression and incident CVD for each trial, before relating the 2 using a Bayesian meta-regression approach. RESULTS We analyzed data of 119 randomized, controlled trials involving 100 667 patients (mean age 62 years, 42% female). Over an average follow-up of 3.7 years, 12 038 patients developed the combined CVD end point. Across all interventions, each 10 μm/y reduction of cIMT progression resulted in a relative risk for CVD of 0.91 (95% Credible Interval, 0.87-0.94), with an additional relative risk for CVD of 0.92 (0.87-0.97) being achieved independent of cIMT progression. Taken together, we estimated that interventions reducing cIMT progression by 10, 20, 30, or 40 μm/y would yield relative risks of 0.84 (0.75-0.93), 0.76 (0.67-0.85), 0.69 (0.59-0.79), or 0.63 (0.52-0.74), respectively. Results were similar when grouping trials by type of intervention, time of conduct, time to ultrasound follow-up, availability of individual-participant data, primary versus secondary prevention trials, type of cIMT measurement, and proportion of female patients. CONCLUSIONS The extent of intervention effects on cIMT progression predicted the degree of CVD risk reduction. This provides a missing link supporting the usefulness of cIMT progression as a surrogate marker for CVD risk in clinical trials.
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Association between caveolin-1 and stroke: a systematic review and meta-analysis.
Geng, T, Feng, L, Fang, YT, Wang, ZQ, Liu, GF
European review for medical and pharmacological sciences. 2020;(19):10054-10060
Abstract
OBJECTIVE Caveolin-1 plays critical roles in regulating signal transduction and cholesterol trafficking in cells. However, the relationship between caveolin-1 and stroke remains less reported. MATERIALS AND METHODS In this study, we reviewed information from seventeen studies to get the qualitative evidence of the influence of the caveolin-1 on stroke and collected data from three of the seventeen studies to conduct meta-analysis. The original studies classified participants into two groups with stroke group and control group, respectively. The random-effect model was used in the meta-analysis with the standardized mean difference (SMD) as the measure indicator. RESULTS Our data showed that the SMD (95% confidence intervals, CIs) between the control group and the stroke group was -0.5449 [-2.3344, 1.0000]. For the subgroup analysis, The SMD (95% confidence intervals, CIs) between the control group and the ischemic stroke group was -1.4589 [-5.0129, 2.0951], and between the control group and the hemorrhagic stroke group was 0.3438 [-0.4140, 1.1017]. CONCLUSIONS Although the differences are not statistically significant between the two groups, the high level of caveolin-1 are associated with the stroke, which may remedy the stroke. Besides, an opposite result was observed for the association of the caveolin-1 on the ischemic stroke and hemorrhagic stroke. To confirm this association, further studies are necessary.
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Impact of Different Doses of Omega-3 Fatty Acids on Cardiovascular Outcomes: a Pairwise and Network Meta-analysis.
Lombardi, M, Chiabrando, JG, Vescovo, GM, Bressi, E, Del Buono, MG, Carbone, S, Koenig, RA, Van Tassell, BW, Abbate, A, Biondi-Zoccai, G, et al
Current atherosclerosis reports. 2020;(9):45
Abstract
PURPOSE OF REVIEW Omega-3 fatty acid (O3FA) supplementation has shown conflicting evidence regarding its benefit in cardiovascular events. We performed a pairwise and network meta-analysis to elucidate the benefit of different doses of O3FA supplementation in cardiovascular prevention. RECENT FINDINGS Fourteen studies were identified providing data on 125,763 patients. A prespecified cut-off value of < 1 g per day was set for low-dose (LD) O3FA and > 1 g per day for high-dose (HD) O3FA. The efficacy outcomes of interest were total death, cardiac death, sudden cardiac death, myocardial infarction, stroke, coronary revascularization, unstable angina, and major vascular events. Safety outcomes of interest were bleeding, gastrointestinal disturbances, and atrial fibrillation events. HD treatment was associated with a lower risk of cardiac death (IRR 0.79, 95% CI [0.65-0.96], p = 0.03 versus control), myocardial infarction (0.71 [0.62-0.82], p < 0.0001 versus control and 0.79 [0.67-0.92], p = 0.003 versus LD), coronary revascularization (0.74 [0.66-0.83], p < 0.0001 versus control and 0.74 [0.66-0.84], p < 0.0001 versus LD), unstable angina (0.73 [0.62-0.86], p = 0.0001 versus control and 0.74 [0.62-0.89], p = 0.002 versus LD), and major vascular events (0.78 [0.71-0.85], p < 0.0001 versus control and 0.79 [0.72-0.88], p < 0.0001 versus LD). HD treatment was associated with increased risk for bleeding events (1.49 [1.2-1.84], p = 0.0002 versus control and 1.63 [1.16-2.3], p = 0.005 versus LD) and increased atrial fibrillation events compared to control (1.35 [1.1-1.66], p = 0.004). HD O3FA treatment was associated with lower cardiovascular events compared to LD and to control, but increased risk for bleeding and atrial fibrillation events.
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Meta-analysis Comparing Direct Oral Anticoagulants Versus Vitamin K Antagonists After Transcatheter Aortic Valve Implantation.
Ueyama, H, Kuno, T, Ando, T, Briasoulis, A, Fox, J, Hayashida, K, Takagi, H
The American journal of cardiology. 2020;(7):1102-1107
Abstract
Atrial fibrillation (AF) is a common co-morbidity in patients undergoing transcatheter aortic valve implantation (TAVI), but whether direct oral anticoagulants (DOACs) confer similar safety and efficacy compared with vitamin K antagonist (VKA) remains unclear in this population. The aim of our study was to investigate the safety and efficacy of DOACs compared with VKA in patients undergoing TAVI with concomitant indication of oral anticoagulation. PUBMED and EMBASE were searched through October 2019 for studies comparing DOACs versus VKA in patients undergoing TAVI with indication of oral anticoagulation. The main efficacy outcomes were all-cause mortality and stroke whereas the main safety outcome was major and/or life-threatening bleeding. Our search identified 5 eligible studies including 2,569 patients. Majority of patients had atrial fibrillation as indication of anticoagulation. There were no significant differences in all-cause mortality, major and/or life-threatening bleeding, and stroke in patients treated with DOACs versus VKA (odds ratio [OR] 1.07, 95% confidence interval [CI] [0.73 to 1.57], p = 0.72, OR = 0.85, 95% CI [0.64 to 1.12], p = 0.24, OR 1.52, 95% CI [0.93 to 2.48], p = 0.09, respectively). In conclusion, in patients undergoing TAVI with concomitant indication for oral anticoagulation, all-cause mortality, major and/or life-threatening bleeding, and stroke were similar between DOACs and VKA. Further large scale randomized controlled trials are needed to search the optimal oral anticoagulation regimen in this population.
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Cholesterol Lowering and Stroke: No Longer Room for Pleiotropic Effects of Statins - Confirmation from PCSK9 Inhibitor Studies.
Salvatore, T, Morganti, R, Marchioli, R, De Caterina, R
The American journal of medicine. 2020;(1):95-99.e6
Abstract
BACKGROUND The relationship between cholesterol levels and stroke has been much less clear than the relationship between cholesterol levels and coronary heart disease. This is likely mostly due to the inadequate power of older studies and the low intensity of cholesterol-lowering interventions available at the time. Because a reduction in stroke has been, conversely, clearly observed in trials with statins, for long "pleiotropic" effects of such drugs, unrelated to cholesterol lowering, have been invoked. In a previous analysis of all randomized trials of cholesterol-lowering treatments reporting on stroke we had, however, reached the conclusion that any cholesterol lowering is related to a significant reduction of stroke, in a relationship that appeared to exist for both statin and nonstatin cholesterol-lowering interventions. Outcome results of the FOURIER trial with evolocumab, SPIRE-1 and -2 with bococizumab, and ODYSSEY OUTCOMES trial with alirocumab now offer the opportunity of clearly confirming or confuting this concept. METHODS We here report on an updated meta-regression of the relationship of total cholesterol changes that occur with various drugs or treatments and changes in the risk of stroke compared with control. RESULTS Relative risk (RR) figure found in FOURIER, SPIRE-1/2, and ODYSSEY OUTCOMES (0.79, 0.60, and 0.79) are extremely close to the RRs of 0.79, 0.79, and 0.84, respectively, predicted by our new meta-regression. CONCLUSIONS These findings offer definitive proof that the pure total (and low-density lipoprotein) cholesterol lowering, with any available lipid-lowering intervention, reduces stroke risk proportional to the extent of cholesterol reduction, without the need of invoking "pleiotropic" effects of any such treatment.