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Clinical Neurology and Neurosurgery Jan 2024Acute ischemic stroke (AIS) is a leading cause of death and disability. AIS is caused by an embolus or thrombus that restricts blood flow to the brain tissue. Despite... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Acute ischemic stroke (AIS) is a leading cause of death and disability. AIS is caused by an embolus or thrombus that restricts blood flow to the brain tissue. Despite intravenous thrombolysis and endovascular thrombectomy, a substantial number of patients do not achieve effective reperfusion. Argatroban, a direct thrombin inhibitor, can potentially improve neurological outcomes in AIS patients. However, there are conflicting results in the medical literature regarding the efficacy and safety of argatroban in this context.
OBJECTIVE
This study aims to evaluate the efficacy and safety of argatroban as monotherapy or adjunct therapy for acute ischemic stroke.
METHODS
Five major databases (PubMed, Embase, Scopus, Web of Science, and Cochrane Library) were searched for randomized controlled trials (RCTs) that compared the efficacy and safety of using argatroban alone or in combination with recombinant tissue plasminogen activator (r-TPA) in the management protocol of the AIS. We used Review Manager Software (RevMan 5.4.1) for data analysis.
RESULTS
We included 1393 patients from eight RCTs (of them, 726 were treated with argatroban alone or combined with r-TPA, while 667 received the placebo, standard therapy (standard treatments based on current guidelines including antihypertensive, antiplatelet agents, and statins) or endovascular r-TPA). Neither argatroban vs control nor argatroban with r-TPA vs r-TPA showed significant difference regarding the activity in daily living; (SMD= 1.69, 95% CI [-0.23, 3.61]; p = 0.09), (SMD= 0.99, 95% CI [-0.88, 2.86]; p = 0.30), respectively. Also, there was no significant difference in the National Institutes of Health Stroke Scale (NIHSS) score at seven days, the number of patients achieving modified Rankin Scale (mRS) of 0-1 or 0-2 at 90 days (p > 0.05). Argatroban did not significantly increase the risk of adverse events or symptomatic intracranial hemorrhage (ICH), or major systemic bleeding compared to control or r-TPA (p > 0.05) CONCLUSIONS: Argatroban does not demonstrate superior efficacy compared to placebo or standard therapy in terms of ADL, NIHSS and mRS outcomes. Importantly, argatroban does not significantly increase the incidence of adverse events, including symptomatic ICH and systemic bleeding.
Topics: Humans; Arginine; Brain Ischemia; Fibrinolytic Agents; Intracranial Hemorrhages; Ischemic Stroke; Pipecolic Acids; Stroke; Sulfonamides; Thrombolytic Therapy; Tissue Plasminogen Activator; Treatment Outcome
PubMed: 38176219
DOI: 10.1016/j.clineuro.2023.108097 -
Angiology Mar 2024Pulmonary embolism (PE) is the third-leading cause of cardiovascular mortality and the second-leading cause of death in cancer patients. The clinical efficacy of... (Review)
Review
Pulmonary embolism (PE) is the third-leading cause of cardiovascular mortality and the second-leading cause of death in cancer patients. The clinical efficacy of thrombolysis for acute PE has been proven, yet the therapeutic window seems narrow, and the optimal dosing for pharmaceutical reperfusion therapy has not been established. Higher doses of systemic thrombolysis inevitably associated with an incremental increase in major bleeding risk. To date, there is no high-quality evidence regarding dosing and infusion rates of thrombolytic agents to treat acute PE. Most clinical trials have focused on thrombolysis compared with anticoagulation alone, but dose-finding studies are lacking. Evidence is now emerging that lower-dose thrombolytic administered through a peripheral vein is efficacious in accelerating thrombolysis in the central pulmonary artery and preventing acute right heart failure, with reduced risk for major bleeding. The present review will systematically summarize the current evidence of low-dose thrombolysis in acute PE.
Topics: Humans; Thrombolytic Therapy; Pulmonary Embolism; Fibrinolytic Agents; Hemorrhage; Treatment Outcome; Acute Disease
PubMed: 37060258
DOI: 10.1177/00033197231167062 -
Thrombosis Research Jan 2024The efficacy of intracoronary (IC) antithrombotic therapy, which may best prevent the no-reflow phenomenon during percutaneous coronary intervention (PCI), remains... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The efficacy of intracoronary (IC) antithrombotic therapy, which may best prevent the no-reflow phenomenon during percutaneous coronary intervention (PCI), remains unclear. Therefore, we compared the efficacy and safety of different IC antithrombotic agents.
MATERIALS AND METHODS
This systematic review and network meta-analysis of randomized controlled trials (RCTs) compared IC fibrinolytic agents (recombinant tissue plasminogen activators [rtPAs] and non-rtPAs) or glycoprotein IIb/IIIa inhibitors (small molecules and monoclonal antibodies) with placebo by searching the relevant studies published before September 21, 2022. Bayesian network meta-analyses were performed using random-effects models.
RESULTS
Twenty-five RCTs with 4546 patients were included. Non-rtPAs and small molecules were significantly more effective in achieving thrombolysis in myocardial infarction (TIMI) grade 3 flow than placebo (odds ratio [OR] 2.28, 95 % credible intervals [CrI] 1.24-4.13; OR 2.06, 95 % CrI 1.17-3.46). Moreover, these agents' efficacy was observed in other microcirculation-related outcomes, including TIMI myocardial perfusion grade 3, complete ST-segment resolution, and corrected TIMI frame counts. Within 6 months, small molecules were associated with both an improved left ventricular ejection fraction (MD 3.90, 95 % CrI 0.48-7.46) and major adverse cardiac events (MACE) reduction (OR 0.36, 95 % CrI 0.20-0.61). Non-rtPAs demonstrated a reduced MACE incidence within 6 months (OR 0.51, 95 % CrI 0.31-0.81). The results were consistent in the subgroup with a total ischemic time > 6 h. No significant differences in mortality or bleeding events were observed.
CONCLUSIONS
IC non-rtPAs and small molecules may be effective for adjunctive therapy to PCI, particularly in patients with longer ischemia periods.
Topics: Humans; ST Elevation Myocardial Infarction; Fibrinolytic Agents; Platelet Aggregation Inhibitors; Network Meta-Analysis; Percutaneous Coronary Intervention; Myocardial Infarction; Treatment Outcome
PubMed: 38041878
DOI: 10.1016/j.thromres.2023.11.022 -
Journal of Clinical Neuroscience :... Sep 2023
Meta-Analysis
Topics: Humans; Urokinase-Type Plasminogen Activator; Ischemic Stroke; Stroke; Brain Ischemia
PubMed: 37419762
DOI: 10.1016/j.jocn.2023.06.020 -
Diabetes, Obesity & Metabolism Jul 2024To conduct a meta-analysis of randomized controlled trials (RCTs) to assess the effect of sodium-glucose cotransporter-2 (SGLT2) inhibitors on inflammatory biomarkers. (Meta-Analysis)
Meta-Analysis
AIMS
To conduct a meta-analysis of randomized controlled trials (RCTs) to assess the effect of sodium-glucose cotransporter-2 (SGLT2) inhibitors on inflammatory biomarkers.
METHODS
Medline, Embase and the Cochrane Library were searched for RCTs investigating the effect of SGLT2 inhibitors on inflammatory biomarkers, adipokine profiles and insulin sensitivity.
RESULTS
Thirty-eight RCTs were included (14 967 participants, 63.3% male, mean age 62 ± 8.6 years) with a median (interquartile range) follow-up of 16 (12-24) weeks. Meta-analysis showed that SGLT2 inhibitors significantly improved adiponectin, interleukin-6, tumour necrosis factor receptor-1 (vs. placebo alone: standardized mean difference [SMD] 0.34 [95% confidence interval {CI} 0.23, 0.45], mean difference [MD] -0.85 pg/mL [95% CI -1.32, -0.38], SMD -0.13 [95% CI -0.20, -0.06], respectively), leptin and homeostatic model assessment of insulin resistance index (vs.
CONTROL
SMD -0.20 [95% CI -0.33, -0.07], MD -0.83 [95% CI -1.32, -0.33], respectively). There were no significant changes in C-reactive protein (CRP), tumour necrosis factor-α, plasminogen activator inhibitor-1, fibroblast growth factor-21 or monocyte chemoattractant protein-1.
CONCLUSIONS
Our analysis shows that SGLT2 inhibitors likely improve adipokine biomarkers and insulin sensitivity, but there is little evidence that SGLT2 inhibitors improve other inflammatory biomarkers including CRP.
Topics: Humans; Sodium-Glucose Transporter 2 Inhibitors; Randomized Controlled Trials as Topic; Biomarkers; Diabetes Mellitus, Type 2; Male; Inflammation; Middle Aged; Female; Insulin Resistance; Aged; C-Reactive Protein; Adiponectin; Plasminogen Activator Inhibitor 1; Interleukin-6; Leptin; Adipokines
PubMed: 38602398
DOI: 10.1111/dom.15586 -
Journal of Stroke and Cerebrovascular... Jul 2024To compare the safety and efficacy of Dual Antiplatelet Therapy (DAPT) and Intravenous (IV) Tissue Plasminogen Activator (t-PA) in minor Acute Ischemic Stroke (AIS). (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To compare the safety and efficacy of Dual Antiplatelet Therapy (DAPT) and Intravenous (IV) Tissue Plasminogen Activator (t-PA) in minor Acute Ischemic Stroke (AIS).
MATERIALS AND METHODS
Following Cochrane and PRISMA guidelines, we analyzed observational studies and clinical trials comparing DAPT and IV t-PA in patients with minor AIS. Databases included PubMed, Scopus, and Web of Science. Data extraction included study characteristics, patient demographics, and analyzed outcomes. RevMan 5.3 and OpenMetaAnalyst 2021 were used to analyze the data and assess heterogeneity, respectively. The risk of bias was determined using RoB 2.0 and the Newcastle-Ottawa scale.
RESULTS
This meta-analysis included five studies with 3,978 DAPT-treated patients and 2,224 IV t-PA-treated patients. We found no significant differences in achieving modified Rankin scale (mRS) scores of 0-1 (OR 1.11, 95 % CI: 0.79, 1.55, p = 0.56) and 0-2 (OR 0.90, 95 % CI: 0.61, 1.31, p = 0.57), as well as combined mRS scores (OR 1.05, 95 % CI: 0.82, 1.34, p = 0.72). Similarly, there were no significant disparities between the two treatment groups in NIHSS score change from baseline (MD 0.32, 95 % CI: -0.35, 0.98, p = 0.35) and in mortality rates (OR 0.87, 95 % CI: 0.26, 2.93, p = 0.83). Notably, in comparison to the IV t-PA group, the DAPT group exhibited a significantly lower incidence of bleeding (OR 0.31, 95 % CI: 0.14, 0.69, p = 0.004) and symptomatic intracranial hemorrhage (sICH) (OR 0.10, 95 % CI: 0.04, 0.26, p < 0.00001).
CONCLUSIONS
Our meta-analysis found no significant differences in efficacy between DAPT and IV t-PA. However, DAPT demonstrated a significantly lower risk of sICH and bleeding compared with IV t-PA.
Topics: Humans; Ischemic Stroke; Tissue Plasminogen Activator; Fibrinolytic Agents; Platelet Aggregation Inhibitors; Treatment Outcome; Dual Anti-Platelet Therapy; Thrombolytic Therapy; Risk Factors; Male; Female; Aged; Middle Aged; Risk Assessment; Disability Evaluation; Administration, Intravenous; Recovery of Function; Observational Studies as Topic; Aged, 80 and over
PubMed: 38561167
DOI: 10.1016/j.jstrokecerebrovasdis.2024.107704 -
Turkish Neurosurgery Feb 2024Extraventricular drainage (EVD) combined with fibrinolytics may prove effective in reducing morbidity and mortality rates associated with intraventricular cerebral...
INTRODUCTION
Extraventricular drainage (EVD) combined with fibrinolytics may prove effective in reducing morbidity and mortality rates associated with intraventricular cerebral hemorrhage (IVH). This efficacy is primarily attributed to increased drainage capacity and a decreased risk of EVD obstruction when fibrinolytics are employed. This systematic review and meta-analysis aimed to determine the effectiveness of thrombolytics in this context.
METHODS
A literature review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO registration number: CRD42022332152). Articles were selected from various sources, including PubMed, Trip Database, LILACS, Cochrane Library, and ScienceDirect. Clinical trials focusing on IVH treatment using EVD and/or fibrinolytics were considered. The Risk of Bias in Non-randomized Studies of Interventions (ROB 2) tool was employed for bias assessment. A fixed-effects regression model was used following heterogeneity analysis. Treatment effectiveness was evaluated based on mortality outcomes.
RESULTS
A total of 531 patients from four studies were included. The use of fibrinolytics significantly decreased IVH mortality compared with a placebo. The odds ratio (OR) for recombinant tissue plasminogen activator (rtPA) or alteplase was 0.54 [0.36; 0.82]. For urokinase (UK), the OR was 0.21 [0.03; 1.54], rendering it statistically non-significant. The overall OR was 0.52 [0.35; 0.78], and the heterogeneity I2 was 0% (indicating low heterogeneity).
CONCLUSION
While EVD alone is a common approach for managing hydrocephalus, its effectiveness is limited by potential blockages and infections. Combining EVD with UK or rtPA demonstrated improved patient outcomes. rtPA stands out as a reliable and effective option, while limited data are available regarding UK\'s effectiveness in reducing IVH mortality.
PubMed: 38874256
DOI: 10.5137/1019-5149.JTN.45919-23.1 -
Repeated intravenous thrombolysis in recurrent ischemic stroke within 3 months: a systematic review.BMC Neurology Nov 2023Repeated intravenous thrombolysis (RIVT) within 3 months is an off-guideline therapy, however, may be an effective and safe way to treat early recurrent ischemic stroke....
BACKGROUND
Repeated intravenous thrombolysis (RIVT) within 3 months is an off-guideline therapy, however, may be an effective and safe way to treat early recurrent ischemic stroke. This study was conducted to assess the potential influencing factors on the efficacy and safety of RIVT in recurrent ischemic stroke within 3 months and to explore the strategy of RIVT within 3 months.
METHODS
PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure, and Wanfang Database were searched for cases of RIVT in recurrent ischemic stroke within 3 months up to February 1, 2023. Clinical characteristics were compared and analyzed between the good-outcome and poor-outcome groups and between the symptomatic intracranial hemorrhage (sICH) and non-sICH groups respectively.
RESULTS
A total of 16 studies including 24 cases of RIVT within 3 months were retrospectively analyzed in the present study. The patients' ages ranged from 42 to 87 years (median 73.5 years) and the intervals between thrombolysis were from 0.25 to 90 days (median 9.5 days). Comparing the clinical characteristics between the good-outcome group and the poor-outcome group, no statistically significant differences were found (P > 0.05), but the differences in baseline National Institutes of Health stroke scale (NIHSS) score of the recurrent stroke (P = 0.056) and good outcome after the previous IVT (P = 0.054) nearly reached statistical significance. Comparing the data between the non-sICH group and the sICH group, statistically significant differences were found in terms of the proportion of cardiogenic embolism (P = 0.036), baseline NIHSS score in the recurrent stroke (P = 0.007) and the interval between thrombolysis (P = 0.041), but no significant difference was found by regression analysis.
CONCLUSION
In patients with recurrent ischemic stroke within 3 months, those with a good outcome after the previous IVT and a low baseline NIHSS score in the recurrent stroke may be considered for RIVT, whereas those with a high baseline NIHSS score, a short interval between thrombolysis, and cardiogenic embolism may suffer a higher risk of sICH. Due to sample size and publication bias, more studies with larger sample sizes and more rigorous designs are needed to confirm this conclusion.
Topics: Humans; Infant; Fibrinolytic Agents; Tissue Plasminogen Activator; Stroke; Thrombolytic Therapy; Brain Ischemia; Retrospective Studies; Ischemic Stroke; Intracranial Hemorrhages; Cerebral Infarction; Embolism; Treatment Outcome
PubMed: 38012577
DOI: 10.1186/s12883-023-03472-4 -
Annals of Vascular Surgery Jan 2024Isolated calf muscular vein thrombosis (ICMVT) can result in pulmonary embolism, but the treatment of ICMVT remains controversial. Therefore, the purpose of the present... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Isolated calf muscular vein thrombosis (ICMVT) can result in pulmonary embolism, but the treatment of ICMVT remains controversial. Therefore, the purpose of the present study was to investigate the optimal treatment for the ICMVT by comparing the efficacy and safety of different treatments.
METHODS
A network meta-analysis was conducted to search for studies published from database inception to April 30, 2022, that compared the outcomes of 2 or more treatments for ICMVT. The primary outcomes were efficacy (resolution rate) and safety (adverse reactions). Data were extracted following predefined hierarchy and the Cochrane Collaboration risk of bias tool was used to evaluate the methodological quality of the included studies. We estimated summary odds ratios with 95% credibility intervals using Bayesian network meta-analysis with random effects.
RESULTS
A total of 16 studies were enrolled in the study. In terms of efficacy and safety, urokinase thrombolysis combined with low-molecular-weight heparin (LMWH) was most effective but had the lowest safety, while physical therapy was safest but had the lowest efficacy. More important, direct oral factor Xa inhibitors were most likely to be second most effective and safe compared with other treatments. For the duration of treatment, anticoagulant therapy for at least 3 months could effectively increase the resolution rate of ICMVT.
CONCLUSIONS
Considering both efficacy and safety, taking direct oral factor Xa inhibitors for at least 3 months was the optimal treatment compared to LMWH, urokinase thrombolysis combined LMWH, physical therapy and warfarin for patients with ICMVT.
Topics: Adult; Humans; Anticoagulants; Heparin, Low-Molecular-Weight; Factor Xa Inhibitors; Urokinase-Type Plasminogen Activator; Network Meta-Analysis; Bayes Theorem; Treatment Outcome; Thrombosis; Venous Thromboembolism
PubMed: 37802136
DOI: 10.1016/j.avsg.2023.08.015 -
Medicine Nov 2023Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory biomarker that is used to predict mortality, readmission, early discharge, and LOS, thus,... (Meta-Analysis)
Meta-Analysis
Role of soluble urokinase type plasminogen activator receptor (suPAR) in predicting mortality, readmission, length of stay and discharge in emergency patients: A systematic review and meta analysis.
BACKGROUND
Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory biomarker that is used to predict mortality, readmission, early discharge, and LOS, thus, serves as a useful tool for ED physicians. Our study aims to analyze the efficacy of suPAR in predicting these prognostic markers in ED.
METHODS
We performed a comprehensive search on 6 databases from the inception to 30th November 2022, to select the following eligibility criteria; a) observation or triage trial studies investigating the role of suPAR levels in predicting: 30 day and 90-day mortality, 30-day readmission, early discharge (within 24hr), and LOS in patients coming to AMU.
RESULTS
A total of 13 studies were included, with a population size of 35,178, of which 52.9% were female with a mean age of 62.93 years. Increased risk of 30-day mortality (RR = 10.52; 95% CI = 4.82-22.95; I2 = 38%; P < .00001), and risk of 90-day mortality (RR = 5.76; 95% CI = 3.35-9.91; I2 = 36%; P < .00001) was observed in high suPAR patients. However, a slightly increased risk was observed for 30-day readmission (RR = 1.50; 95% CI = 1.16-1.94; I2 = 54%; P = .002). More people were discharged within 24hr in the low suPAR level group compared to high suPAR group (RR = 0.46; 95% CI = 0.40-0.53; I2 = 41%; P < .00001). LOS was thrice as long in high suPAR level patients than in patients with low suPAR (WMD = 3.20; 95% CI = 1.84-4.56; I2 = 99%; P < .00001).
CONCLUSION
suPAR is proven to be a significant marker in predicting 30-day and 90-day mortality in ED patients.
Topics: Humans; Female; Middle Aged; Male; Receptors, Urokinase Plasminogen Activator; Patient Discharge; Patient Readmission; Length of Stay; Biomarkers; Prognosis
PubMed: 37960735
DOI: 10.1097/MD.0000000000035718