Acute Ischemic Stroke In China Research Articles

Tenecteplase thrombolytic therapy for acute ischaemic stroke in China: a real-world, multicentre, retrospective, controlled study

Background and aimsTenecteplase (TNK) offers logistical advantages in stroke thrombolytic therapy with its single bolus administration compared with alteplase. We aim to investigate the real-world evidence regarding its safety and effectiveness in China.MethodsWe conducted a retrospective study on patients receiving alteplase or TNK for acute ischaemic stroke (AIS) within 4.5 hours of onset between 1 March 2019 and 1 October 2023, from 18 stroke centres in China. Using propensity score matching (PSM), TNK-treated patients were matched 1:1 with alteplase-treated patients. The primary outcome was the rate of symptomatic intracranial haemorrhage (sICH) within 72 hours post-thrombolysis. Secondary outcomes comprised the rate of parenchymal haemorrhage type 2, any intracranial haemorrhage, any systematic bleeding and mortality at 90 days, as well as 24-hour National Institutes of Health Stroke Scale (NIHSS), early neurological improvement at 24 hours, modified Rankin Scale (mRS) shift, percentage of mRS 0–1 and mRS 0–2 at 90 days.ResultsWe identified 1113 patients with AIS who received TNK and 2360 patients who received alteplase. Following PSM, 1113 TNK-treated patients with AIS were matched to 1113 patients treated with alteplase. No significant differences were observed in rates of sICH (1.8% vs 1.98%, p=0.864) or other safety outcomes. Moreover, TNK-treated patients demonstrated a lower rate of any intracranial haemorrhage (OR: 0.51, 95% CI: 0.31 to 0.86, p=0.012). A higher proportion of patients achieving early neurological improvement at 24 hours (OR: 1.76, 95% CI: 1.48 to 2.09, p=0.000), better 90-day mRS (OR: 0.67, 95% CI: 0.57 to 0.79, p=0.000) as well as higher percentages of 90-day mRS 0–1 (OR: 1.27, 95% CI: 1.05 to 1.54, p=0.012) and mRS 0–2 (OR: 1.41, 95% CI: 1.14 to 1.75, p=0.001) compared with alteplase.ConclusionsThrombolysis with TNK is not associated with an increased risk of sICH, and may result in better early neurological improvement and 90-day functional outcomes compared with alteplase in patients with AIS.

Glycated albumin levels are associated with adverse stroke outcomes in patients with acute ischemic stroke in China.

Glycated albumin (GA) is a biomarker monitoring glycemia 2-4 weeks before stroke onset. This study was designed to explore the association between GA levels with poststroke outcomes in patients with acute ischemic stroke or transient ischemic attack (TIA). Participants with ischemic stroke or TIA who had a baseline GA measurement were included in the Third China National Stroke Registry study. The effect of GA on stroke recurrence, poor functional outcomes, and combined vascular events was examined during the 1-year follow-up period. Multivariate Cox and logistic regression models were performed to evaluate the association. Discrimination tests were used to examine the incremental predictive value of GA when incorporating it into the conventional model. A total of 3861 participants were enrolled. At the 3-month follow-up, the elevated GA level was associated with an increased risk of poor functional outcomes (adjusted odds ratio [OR], 1.45; 95% confidence interval [CI], 1.01-2.09). A similar increase was observed for stroke recurrence (adjusted hazard ratio [HR], 1.56; 95% CI, 1.09-2.24), poor functional outcomes (adjusted OR, 1.62; 95% CI, 1.07-2.45), and combined vascular events (adjusted HR, 1.55; 95% CI, 1.09-2.20) at the 1-year follow-up. In nondiabetic patients, the association between GA and poor functional outcomes was more pronounced (adjusted OR, 1.62; 95% CI, 1.05-2.50). Adding GA into the conventional model resulted in slight improvements in predicting poor functional outcomes (net reclassification improvement [NRI]: 12.30% at 1 year). This study demonstrated that elevated GA levels in serum were associated with stroke adverse outcomes, including stroke recurrence, poor functional outcomes, and combined vascular events, in patients with ischemic stroke or TIA.

Cost-effectiveness of endovascular treatment for acute ischemic stroke in China: evidence from Shandong Peninsula

BackgroundRecently, the endovascular treatment (EVT) of acute ischemic stroke has made significant progress in many aspects. Intravenous thrombolysis (IVT) is usually recommended before endovascular treatment in clinical practice, but the value of the practice is controversial. The latest meta-analysis evaluation was that the effect of EVT versus EVT plus IVT did not differ significantly. The cost-effectiveness analysis of EVT plus IVT needs further analysis. This study assesses the health benefits and economic impact of EVT plus IVT in Shandong Peninsula of China.MethodWe followed a cross-section design using the Chinese-Shandong Peninsula public hospital database between 2013 and 2023. The real-world costs and health outcomes were collected through the Hospital Information System (HIS) and published references. We calculated incremental cost-effectiveness ratios (ICERs) from the perspective of Chinese healthcare using the complex decision model to compare the costs and effectiveness between EVT versus EVT + IVT. One-way and Monte Carlo probabilistic sensitivity analyses were performed to assess the robustness of the economic evaluation model.ResultsEVT alone had a lower cost compared with EVT + IVT whether short-term or long-term. Until 99% dead of AIS patients, the ICER per additional QALY was RMB696399.30 over the willingness-to-pay (WTP) threshold of 3× gross domestic product (GDP) per capita in Shandong. The probabilistic sensitivity analysis of 3 months, 1 year and long-term horizons had a 97.90%, 97.43% and 96.89% probability of cost-effective treatment under the WTP threshold (1×GDP). The results of the one-way sensitivity analysis showed that direct treatment costs for EVT alone and EVT + IVT were all sensitive to ICER.ConclusionsEVT alone was more cost-effective treatment compared to EVT + IVT in the Northeast Coastal Area of China. The data of this study could be used as a reference in China, and the use of the evaluation in other regions should be carefully considered.

Impact of remote ischemic postconditioning on acute ischemic stroke in China: a systematic review and meta-analysis of randomized controlled trials

ObjectiveAcute ischemic stroke (AIS) is a significant health burden in China, affecting a sizable portion of the population. Conventional pharmacological treatments frequently fall short of desirable outcomes. Therefore, exploring alternative therapies is crucial. Remote ischemic postconditioning (RIPostC) is a noninvasive and cost-effective adjunctive therapy. This study aimed to investigate the efficacy and safety of RIPostC as an adjunctive therapy for AIS to inform clinical practice.MethodsA comprehensive search was conducted across the PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), WanFang, Weipu (VIP), and China Biology Medicine disc (CBM) databases up to October 2023. All included studies underwent bias risk assessment using the Cochrane risk-of-bias assessment tool. The primary outcome measure was the National Institute of Health Stroke Scale (NIHSS), with secondary outcomes including the Barthel index (BI), D-dimer, C-reactive protein (CRP), fibrinogen (FIB), brain-derived neurotrophic factor (BDNF), modified Rankin scale (mRS), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) levels. The data were analyzed using fixed-effects and random-effects models in Review Manager, with mean differences (MDs) and 95% confidence intervals (CIs) calculated for each outcome. The grading of recommendations, assessment, development, and evaluations (GRADE) approach was used to evaluate the level of evidence for each outcome measure.ResultsThis meta-analysis included 38 studies, encompassing 4334 patients. Compared with the control group, the RIPostC group had significantly lower NIHSS scores, serum CRP, D-dimer, IL-6, TNF-α, and FIB levels, and increased BDNF levels. Moreover, it improved the patient’s BI and mRS scores. According to the GRADE approach, the quality of evidence for mRS was deemed “moderate,” while the NIHSS, BI, and CRP were rated as “low” quality. IL-6, TNF-α, FIB, D-dimer, and BDNF received “very low” quality ratings.ConclusionThe findings suggest that RIPostC activates endogenous protective mechanisms, providing benefits to patients with AIS.

Correlation between plasma lipoprotein-associated phospholipase A2 levels and risk of ischaemic stroke recurrence by gender in the Chinese population

ABSTRACT Objective To investigate the correlation between gender differences in plasma lipoprotein phospholipase A2 (Lp-PLA2) levels and the risk of recurrent stroke in patients with acute ischaemic stroke in China. Methods We conducted a prospective follow-up study that included baselineLp-PLA2 levels and NIH Stroke Scale (NIHSS) scores in patients with ischaemic stroke upon admission. The diagnostic efficacy of the baseline Lp-PLA2 level for stroke recurrence was evaluated. And Kaplan‒Meier method was used to analyse the difference in the risk of recurrent stroke between these two groups among males and females. A paired t test was used to analyse the difference in Lp-PLA2 levels in male and female patients after follow-up. Results Baseline plasma Lp-PLA2 was higher in men and women with recurrent stroke than in those without recurrent stroke. The correlation between baseline Lp-PLA2 and neurological impairment was higher in female than male stroke patients (R = 0.338 and 0.253, respectively). Although weakly correlated with neurological impairment, baseline Lp-PLA2 was more effective in predicting recurrent stroke (AUC = 0.705 in men, 0.788 in women). A Cox model was used to compare the risk of stroke between the high- and low-Lp-PLA2 groups (OR = 3.98 in men, 2.61 in women). According to the follow-up time of 6 months as the node, Lp-PLA2 will give different risk indicators. Conclusion Elevated plasma Lp-PLA2 is an independent risk factor for recurrent ischaemic stroke but is not strongly associated with the degree of cerebral damage. The predictive value of baseline Lp-PLA2 for stroke recurrence risk was higher in females than in males.

Assessment of rehabilitation following acute ischaemic stroke in China: a registry-based retrospective observational study

ObjectivesThis study aimed to describe the frequency, determinants and outcomes for assessment of patients who had an acute ischaemic stroke (AIS) for rehabilitation during hospitalisation in China.DesignA registry-based retrospective observational...

Geographic differences in pharmacotherapy patterns and outcomes of acute ischemic stroke in China

BackgroundVast economic and healthcare status discrepancies exist among regions in China, contributing to different treatment patterns. This study was aimed to investigate the current status of pharmacotherapy for acute ischemic stroke (AIS) and outcomes in China and explore the geographic variation in stroke care.MethodsThis study was a multicenter prospective registry study, which collected the data of patients with AIS from 80 hospitals in 46 cities in 2015–2017 across China. Poor functional outcome defined as a modified Rankin Scale score of 3–6 was assessed at 3 and 12 months. Multivariate logistic regression was used.ResultsAmong 9973 eligible patients, the number of receiving intravenous thrombolysis (IVT), antiplatelet agents, anticoagulants, statin and human urinary kallidinogenase was 429 (4.3%), 9363 (93.9%), 1063 (10.7%), 6828 (74.7%) and 5112 (51.2%), respectively. Multivariable analysis showed IVT use in northeastern was significantly more frequent than in eastern region (OR = 3.17, 95% CI, 2.53–3.99), while the antiplatelets agents use were less frequent (OR = 0.46, 95%CI: 0.38–0.57). The proportions of poor outcomes at 3 and 12 months were 20.7% and 15.8%, respectively. Multivariate analysis showed AIS patients from northeastern and central region had significantly lower risk of poor outcome at month 3 and 12 than those from eastern region (all P < 0.05).ConclusionsThere was a low IVT use and a high antiplatelet agent and statin use for AIS in China. The pharmacotherapy and prognosis of AIS had variation by geographic region.Trial registrationThis study was registered with ClinicalTrials.gov (NCT02470624).

A retrospective study on the prevalence and risk factors of neurogenic lower urinary tract dysfunction for acute ischemic stroke in China: A case-control study.

This study identified risk factors for neurogenic lower urinary tract dysfunction (NLUTD) in patients with acute ischemic stroke (AIS) through multidimensional analysis of the medical records of patients, aiming to reduce the incidence of NLUTD, improve prognosis, and facilitate rehabilitation. In this case-control study, patients with AIS were recruited from two tertiary general hospitals in Shenzhen, China, from March 2021 to October 2023. Patients were divided into NLUTD and non-NLUTD groups based on the presence and absence of NLUTD, respectively. Comparative analysis was performed using the Mann-Whitney U and chi-square tests, with significant variables being included in logistic regression analysis. Of the 652 participants enrolled in this study, 119 participants (18.3%) developed NLUTD. Bivariate analysis showed that 39 of 54 screened factors exhibited a significant correlation (p<0.05) with the incidence of NLUTD after AIS. Significant variables identified through logistic regression analysis included Glasgow coma scale (GCS) and National Institutes of Health Stroke Scale (NIHSS) scores, anemia, aphasia, pneumonia, brainstem involvement, multiple lesions, urine clarity (CLA), random venous blood glucose (GLU) and hemoglobin (HGB) levels, and white blood cell (WBC) count. A total of 11 risk factors for NLUTD were identified in this study. This finding provides valuable guidance for reducing the incidence of NLUTD after AIS and improving the quality of life of patients.

Anisodine hydrobromide injection in the treatment of acute ischemic stroke: A protocol for systematic review and meta-analysis

Background: Acute ischemic stroke (AIS) is a common disease of the central nervous system, with high mortality, and disability rates. Anisodine hydrobromide (Ani) injection has been used clinically for the treatment of AIS in China. However, no systematic review and meta-analysis have provided rigorous evidence for the clinical use of Ani injection in the treatment of AIS. This study aims to assess the efficacy and safety of Ani injection in the treatment of AIS. Methods: Following databases will be searched to identify eligible articles: CNKI, VIP, Wanfang, Chinese Biomedical Literature Database, EMBASE, PubMed, Cochrane, and Web of Science. All databases will be searched from their inception to May, 2023. RevMan software will be used for data analysis. Results: The results from meta-synthesis and descriptive analysis of National Institute of Health Stroke Scale, modified Rankin scale, Barthel Index, CT parameters, clinical efficacy rate, and adverse reactions of included articles will provide latest evidence. Conclusion: Findings of this study will provide a solid evidence-based basis for the rational and precise application of Ani injection for the treatment of AIS.

Endovascular Treatment for Acute Ischemic Stroke in China: a study protocol for a prospective, national, multi-center, registry study.

Endovascular treatment (EVT) is the standard treatment for acute ischemic stroke (AIS) patients with large vessel occlusion (LVO). Endovascular Treatment for Acute Ischemic Stroke in China (DETECT2-China) aims to evaluate real-world outcomes and safety of EVT for LVO-AIS patients in China. DETECT2-China is a prospective, national, multi-center study registered in ClinicalTrials.gov (NCT05092139). This study plans to enroll a total of 3,000 consecutive patients who received EVT for LVO. All eligible patients are adults aged 18 years or older with acute LVO who received EVT and standard medical treatment according to the Chinese stroke guidelines and local practice. The primary outcome is functional independence (modified Rankin Scale score, mRS ≤ 2) at 90 days. The secondary outcomes include (1) the proportion of patients with mRS scores of 0-1 at 90 days, (2) distribution of mRS at 90 days, (3) changes in National Institutes of Health stroke scale (NIHSS) at 24 h, 48 h, and 12 days or discharge (whichever is earlier), (4) the proportion of symptomatic intracranial hemorrhage (sICH) within 48 h, and (5) the proportion of death within 7 days. The DETECT2-China will provide real-world data about the effectiveness and safety of EVT for AIS-LVO patients in China.

Indobufen versus aspirin in patients with acute ischaemic stroke in China (INSURE): a randomised, double-blind, double-dummy, active control, non-inferiority trial

Aspirin is recommended for secondary stroke prevention in patients with moderate-to-severe ischaemic stroke but can lead to gastrointestinal intolerance and bleeding. Indobufen is used as an alternative antiplatelet agent in some countries, despite an absence of large-scale clinical trials for this indication. We tested the hypothesis that indobufen is non-inferior to aspirin in reducing the risk of new stroke at 90 days in patients with moderate-to-severe ischaemic stroke. We conducted a randomised, double-blind, double-dummy, active control, non-inferiority trial at 163 tertiary and district general hospitals in China. Eligible participants were aged 18-80 years with acute moderate-to-severe ischaemic stroke (National Institutes of Health Stroke Scale score 4-18). We randomly assigned (1:1) participants within 72 h of the onset of symptoms to receive either indobufen (100 mg tablet twice per day) or aspirin (100 mg tablet once per day) for 90 days. The randomisation sequence was computer generated centrally and stratified by local participating centres. Masked local investigators assigned the random code to patients in ascending order and provided a treatment kit corresponding to the random code. The primary efficacy outcome was new stroke and the primary safety outcome was severe or moderate bleeding, both within 90 days. This primary efficacy outcome was assessed in all randomly assigned and consenting patients and in a per-protocol group (ie, all patients finishing the treatment without major violation of the trial protocol). Safety analyses were done in the safety-analysis population (ie, all patients who received at least one dose of the study drug and had a safety assessment available). We assessed the non-inferiority of indobufen versus aspirin using the one-sided upper limit of the 95% CI of the hazard ratio (HR) with a prespecified non-inferiority margin of 1·25. This trial is registered with ClinicalTrials.gov (NCT03871517). This trial took place between June 2, 2019, and Nov 28, 2021. Of 84 093 patients screened, 5438 patients were randomly assigned to receive either indobufen (n=2715) or aspirin (n=2723), all of whom were included in the primary analyses. Median age was 64·2 years (IQR 56·1-70·6); 1921 (35·3%) were women and 3517 (64·7%) were men. Stroke occurred within 90 days in 213 (7·9%) patients in the indobufen group versus 175 (6·4%) in the aspirin group (HR 1·23, 95% CI 1·01-1·50; pnon-inferiority=0·44). Moderate or severe bleeding occurred in 18 (0·7%) patients in the indobufen group and in 28 (1·0%) in the aspirin group (0·63, 95% CI 0·35 to 1·15; p=0·13). Adverse events within 90 days occurred in 666 (24·5%) patients in the indobufen group and 679 (24·9%) patients in the aspirin group (p=0·73). In patients with acute moderate-to-severe ischaemic stroke, indobufen was not non-inferior to aspirin because the upper limit of the 95% CI was greater than 1·25. Furthermore, indobufen seemed to be inferior to aspirin in reducing the risk of recurrent stroke at 90 days because the lower limit of the 95% CI was greater than 1·00. Although moderate or severe bleeding did not differ between groups, these findings do not support the use of indobufen for secondary stroke prevention in patients with moderate-to-severe ischaemic stroke. Hangzhou Zhongmei Huadong Pharmaceutical and Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences. For the Chinese translation of the abstract see Supplementary Materials section.

Qixue Shuangbu decoction and acupuncture combined with Western medicine in acute severe stroke patients.

Stroke is a common and frequently occurring disease of the nervous system and one of the three major diseases leading to human death. The incidence and mortality of stroke in China increase with age. Overall, 70 % of patients with stroke have serious disability, which results in heavy burden to their families and the society. To analyze the effects of Qixue Shuangbu decoction and acupuncture combined with Western medicine on immune indexes and digestive tract function in patients with acute severe stroke. A total of 68 patients with acute severe stroke admitted to Lanzhou Second People's Hospital between March 2018 and September 2021 were selected and divided into the control and observation groups according to a random number table method. The control group was administered routine Western medicine treatment, such as dehydration, lowering intracranial pressure, anticoagulation, improving cerebral blood circulation and cerebral nerve protection according to the "Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke in China." The observation group was administered Qixue Shuangbu decoction via nasal feeding tube on the basis of the routine Western medicine treatment with simultaneous acupuncture. The two groups were compared. The acute physiology and chronic health evaluation II, organ dysfunction syndrome score, National Institutes of Health Stroke Scale, and traditional Chinese medicine syndrome scores of the two groups were significantly decreased compared with those measured before treatment, and the complements C3 and C4, and immunoglobulins (Ig) M and G were significantly increased compared with those observed before treatment (P < 0.05). After treatment, the scores of the observation group were lower than those of the control group, and the complement and Ig levels were higher than those of the control group (P < 0.05). The levels of diamine oxidase (DAO), D-lactic acid (D-LA), and calcitonin gene-related peptide (CGRP) in the two groups were significantly higher than those before treatment, while the levels of lipopolysaccharide, ubiquitin carboxyl-terminal hydrolase 1 (UCH-L1), tumor necrosis factor-α (TNF-α), interleukin (IL) -2, and IL-8 were significantly lower than those before treatment (P < 0.05). After treatment, DAO, D-LA, and CGRP were higher in the observation group than in the control group, while lipopolysaccharide, UCH-L1, TNF-α, IL-2, and IL-8 were lower than in the control group (P < 0.05). The hospitalization time of individuals in the observation group was shorter than that of the control group (P < 0.05). Qixue Shuangbu decoction and acupuncture combined with Western medicine for the treatment of acute severe stroke can regulate intestinal flora, reduce inflammation, improve intestinal mucosal barrier function and immune function related indicators, and promote recovery.

Proteomic Analysis of Protective Effects of Dl-3-n-Butylphthalide against mpp + -Induced Toxicity via downregulating P53 pathway in N2A Cells

BackgroundDl-3-n-butylphthalide (NBP) is an important medial therapy for acute ischemic stroke in China. Recent studied have revealed that NBP not only rescued the loss of dopaminergic neurons in cellular and animal models of Parkinson's disease (PD), but also could improve motor symptoms in PD patients. However, the protective mechanism is not fully understood. P53 is a multifunctional protein implicated in numerous cellular processes, including apoptosis, DNA repair, mitochondrial functions, redox homeostasis, autophagy and protein aggregations. In PD, p53 integrated with various neurodegeneration-related signals inducing neuronal loss, indicating the suppression of P53 might be a promising target for PD treatment. Therefore, the purpose of the current study was to systemically screen new therapeutic targets of NBP in PD.MethodIn our study, we constructed mpp + induced N2A cells to investigate the benefit effect of NBP in PD. MTT assay was performed to evaluate the cell viability; TMT-based LC–MS/MS was applied to determine the different expressed proteins (DEPs) of NBP pretreatment; online bioinformatics databases such as DAVID, STRING, and KEGG was used to construe the proteomic data. After further analyzed and visualized the protein–protein interactions (PPI) by Cytoscape, DEPs were verified by western blot.ResultA total of 5828 proteins were quantified in the comparative proteomics experiments and 417 proteins were considered as DEPs (fold change > 1.5 and p < 0.05). Among the 417 DEPs, 140 were upregulated and 277 were downregulated in mpp + -induced N2A cells with NBP pretreatment. KEGG pathway analysis indicated that lysosome, phagosome, apoptosis, endocytosis and ferroptosis are the mainly enriched pathways. By using MCL clustering in PPI analysis, 48 clusters were generated and the subsequent KEGG analysis of the top 3 clusters revealed that P53 signaling pathway was recognized as the dominant pathway for NBP treatment.ConclusionNBP significantly relived mpp + -induced cell toxicity. The neuroprotective role of NBP was implicated with P53 signaling pathway in some extent. These findings will reinforce the understanding of the mechanism of NBP in PD and identify novel therapeutic targets.

Association of Proton Pump Inhibitor Prophylaxis on Clinical Outcome in Acute Ischemic Stroke in China: A Multicenter Retrospective Cohort Study

Overtreatment with proton pump inhibitors (PPIs) in acute ischemic stroke (AIS) patients continues to grow. We aimed to investigate the frequency of PPI prophylaxis without an appropriate indication in AIS patients in China and clarify the association between PPI prophylaxis and long-term prognosis. Based on a multicenter stroke registry database, neurological outcomes, stroke events, recurrent ischemic strokes, and all-cause death were compared between patients with and without PPI prophylaxis. A total of 4542 AIS were included, and 3335 (73.4%) received PPI prophylaxis. Patients with PPI prophylaxis were more likely to have a poor outcome at 1 year than those without PPI prophylaxis (33.3% vs. 25.8%, OR 1.321; 95% CI 1.102-1.584; p = 0.003). No significant differences were found in all-cause death, stroke event, or recurrent ischemic stroke at 1 year between the two groups. After propensity score matching, PPI prophylaxis was still independently associated with a higher rate of poor outcome (30.9% vs. 25.8%, OR 1.432; 95% CI 1.151-1.780; p = 0.001). Sensitivity analysis also showed that PPI prophylaxis increased the rate of a poor outcome in minor strokes or at different durations of PPI prophylaxis. Approximately 3/4 of AIS patients were given PPI prophylaxis during hospitalization, which was associated with a poor long-term outcome.

Cost-effectiveness of edaravone dexborneol versus edaravone for the treatment of acute ischemic stroke in China: Based on the TASTE study.

Background and purpose: The TASTE trial indicated that patients with acute ischemic stroke (AIS) using edaravone dexborneol have a significantly higher proportion of 90-day good functional outcomes (mRS 0-1) than those using edaravone. This study compared the cost-effectiveness of the aforementioned interventions in treating AIS in the Chinese setting, aiming to inform treatment decisions in clinical practice. Methods: A model combining a decision tree and a Markov model was developed to assess the cost-effectiveness of edaravone dexborneol versus edaravone for AIS over a 30-year time horizon from the Chinese healthcare system's perspective. Both efficacy and safety data were extracted from the TASTE study. Local costs and utilities were derived from publications and open-access databases; both cost and effectiveness were discounted at a rate of 5% per year. Sensitivity analyses were conducted to ensure robustness and identify the main drivers of the result. Results: Compared with edaravone, edaravone dexborneol for AIS was found to be cost-effective in the first year and highly cost-effective as the study time horizons extended. In the long term (30 years), edaravone dexborneol yielded a lifetime gain of 0.25 (0.07-0.45) quality-adjusted life years (QALYs) at an additional cost of CNY 2201.07 (-3,445.24-6,637.23), yielding an ICER of CNY 8823.41 per QALY gained under the willingness-to-pay (WTP) of 1.5 times per capita GDP (121,464 CNY). The result is robust in both deterministic and probabilistic sensitivity analysis (PSA) methods, with the advantage of the edaravone dexborneol strategy increasing over time. Specifically, the probability of edaravone dexborneol dominant dexborneol is 76.30%, 98.90%, and 99.50% over 1-, 5-, and 30-year time horizons. Conclusion: Both short- and long-term economic analyses suggest that edaravone dexborneol is highly likely to be a cost-effective alternative to treat AIS compared with edaravone in China.

Somatic mutation contributing to clonal haematopoiesis is a risk factor of recurrent stroke in first-ever acute ischaemic stroke: a prospective cohort study

BackgroundSomatic mutation contributes to clonal haematopoiesis of indeterminate potential (CHIP) is related to age and associated with a higher risk of stroke and atherosclerotic cardiovascular disease. Here, we investigated the...

Cost-Effectiveness of Low-Dose Compared to Standard-Dose Alteplase for Acute Ischemic Stroke in China: A Within-Trial Economic Evaluation of the ENCHANTED Study

Introduction: The Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED) showed that a low-dose alteplase was safe but not clearly non-inferior to standard-dose alteplase in acute ischemic stroke (AIS). Given the significant cost of this medicine, we undertook a cost-effectiveness analysis to determine the probability that low-dose is cost-effective relative to standard-dose alteplase in China. Methods: For ENCHANTED participants in China with available health cost data, cost-effectiveness and cost-utility analyses were undertaken in which death or disability (modified Rankin scale scores 2–6) at 90 days and quality-adjusted life-years (QALYs) were used as outcome measures, respectively. There was adherence to standard guidelines for health economic evaluations alongside non-inferiority trials and according to a health-care payer’s perspective. The equivalence margin for cost and effectiveness was set at USD 691 and −0.025 QALYs, respectively, for the base-case analysis. Probabilistic sensitivity analyses were used to evaluate the probability of low-dose alteplase being non-inferior. Results: While the mean cost of alteplase was lower in the low-dose group (USD 1,569 vs. USD 2,154 in the standard-dose group), the total cost was USD 56 (95% confidence interval [CI]: −1,000–1,113) higher compared to the standard-dose group due to higher hospitalization costs in the low-dose group. There were 462 (95% CI: 415–509) and 410 (95% CI: 363–457) patients with death or disability per 1,000 patients in the low-dose and standard-dose groups, respectively. The low-dose group had marginally lower (0.008, 95% CI: −0.016–0.001) QALYs compared to their standard-dose counterparts. The low-dose group was found to have an 88% probability of being non-inferior based on cost-effectiveness versus the standard-dose group. Conclusions: This health economic evaluation alongside the ENCHANTED indicates that the use of low-dose alteplase does not save overall healthcare costs nor lead to a gain in QALYs in the management of Chinese patients with AIS compared to the use of standard dose. There is little justification on economic grounds to shift from standard-of-care thrombolysis in AIS.

Efficacy and safety of butylphthalide in secondary prevention of stroke: study protocol for a multicenter, real world trial based on Internet

BackgroundAs one of the leading causes of morbidity and mortality, stroke and its recurrence has attracted more and more attention. Dl-3-n-butylphthalidle(NBP) has been widely used for treating acute ischemic stroke in China and shows a great clinical effect. NBP plays a role in different pathophysiological processes in the treatment of ischemic stroke, including antioxidants, anti-inflammatory, anti-apoptotic, anti-thrombosis, and mitochondrial protection. Many randomized, double-blind, placebo-controlled, multicenter clinical trials suggest that NBP is a safe and effective treatment for ischemic stroke. To sum up, the current research is mainly focused on the short-term treatment of stroke patients with RCT (randomized controlled trial). Therefore, we designed this study to confirm the role of butylphthalide in secondary stroke prevention in the real world.MethodsThis study will be a multicenter, prospective real-world trial. We would recruit 8000 patients with ischemic stroke from 78 public hospitals in China. All participants will be allocated to one of two parallel treatment groups according to their own wills: (1) butylphthalide group: 0.2 g of butylphthalide capsules three times daily plus routine treatment (aspirin 50-300 mg/d, clopidogrel 75 mg/d, etc.); (2) control group: routine treatment (aspirin 50-300 mg/d, clopidogrel 75 mg/d, etc.). Treatment duration is 90 consecutive days or more. The primary outcome is recurrence rate of stroke within 1 month, 3 months, 6 months and 1 year in butylphthalide group and control group. The secondary outcomes included NIHSS score, the mRS score, other clinical cardiovascular events within one year (sudden death / myocardial infarction / arrhythmia / heart failure, etc.), and adverse events of patients in groups. NIHSS will be captured in the first month after discharge, and the others will be captured at the same time points as the primary end point.DiscussionThis trial will be exploring the efficacy and safety of butylphthalide in secondary prevention of ischemic stroke to expand the scope of application of butylphthalide soft capsules and provide new ideas for enriching the secondary prevention of stroke.Trial registrationChinese Clinical Trial Registry (ChiCTR). Trial registration number: ChiCTR2000034481. Registered on 6 July 2020, http://www.chictr.org.cn/showproj.aspx?proj=55800

Early neurological deterioration in acute ischemic stroke patients after intravenous thrombolysis with alteplase predicts poor 3-month functional prognosis - data from the Thrombolysis Implementation and Monitor of Acute Ischemic Stroke in China (TIMS-China)

BackgroundWe aimed to investigate the risk factors of early neurological deterioration (END) after intravenous thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) and the relationship between END and poor 3-month functional outcomes.MethodsPatients who accepted intravenous recombinant rt-PA were enrolled continuously. END was defined as an increase in National Institute of Health Stroke (NIHSS) score ≥ 4 points or death within 24 hours after intravenous thrombolysis. The modified Rankin Scale (mRS) score was recorded to evaluate the functional outcome of stroke, and the poor 3-month prognosis was defined as an mRS score ≥ of 3. Univariate and multivariate analyses were used to analyze the risk factors of END. The relation between END and 3-month functional outcome was analyzed by multivariate logistic regression analysis.ResultsA total of 1107 patients (mean age, 63.42 ± 11.33 years; 673 males) were included in the final analysis, and 81(7.32%) patients had END. In multivariate analysis, the serum glucose level was significantly associated with END; the odds ratio was 1.10 (95% CI 1.03 to 1.18, p = 0.004). The multivariate logistic analysis showed END has a notable association with the poor 3-month functional recovery even after adjusting for confounding factors; the adjusted OR was 8.25 (95% CI 3.77 to 18.03, p < 0.0001).ConclusionsThe initial serum glucose level might be an independent risk factor of END, and END might predict a poor 3-month prognosis.

Dl-3-n-butylphthalide attenuates myocardial ischemia reperfusion injury by suppressing oxidative stress and regulating cardiac mitophagy via the PINK1/Parkin pathway in rats.

BackgroundAcute myocardial infarction (AMI) is one of the leading causes of mortality worldwide. Undesirable myocardial damage may occur during reperfusion of the ischemic myocardium, and this is known as “ischemic reperfusion injury” (IRI). Currently, there are few effective drugs to alleviate IRI. Dl-3-n-butylphthalide (NBP) is recommended for the treatment of acute ischemic stroke in China. This study investigated the effects of NBP on IRI and its underlying mechanisms.MethodsThe left anterior descending (LAD) coronary arteries of rats were occluded for 30 minutes and reperfused for 6 hours to establish the ischemia/reperfusion (I/R) model. NBP was administered intraperitoneally 2 hours before modeling and immediately after reperfusion. At 6 hours after reperfusion, 2,3,5-triphenyltetrazolium chloride (TTC) staining, enzyme-linked immunosorbent assay (ELISA), oxidative stress index, myocardial injury index, hematoxylin and eosin (HE) staining, transmission electron microscopy (TEM), real-time polymerase chain reaction (PCR), immunofluorescence staining, and Western blot analyses were performed to investigate the protective effects of NBP against IRI.ResultsIn the rat I/R model, NBP remarkably reduced the myocardial infarct size, alleviated myocardial injury and oxidative stress, improved the pathological alteration of cardiomyocytes and mitochondria, and upregulated mitophagy. In addition, the study demonstrated that the protective effects of NBP against IRI involved mitophagy mediated by the PTEN-induced putative kinase protein-1 (PINK1)/Parkin signaling pathway.ConclusionsNBP was able to protect the myocardium from IRI in rats through inhibiting oxidative stress and activating mitophagy, mediated by the PINK1/Parkin pathway.