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Outcomes and Treatment Complications of Intravenous Urokinase Thrombolysis in Acute Ischemic Stroke in China.

ABSTRACT: Background: Intravenous thrombolysis with alteplase benefits eligible patients with acute ischemic stroke. However, in some countries such as China, alteplase may be too expensive for low-income patients, and also for regions with low economic development. Urokinase is much less expensive than alteplase. This study aimed to assess the outcomes and treatment complications of urokinase in acute ischemic stroke patients, which are poorly understood. Methods: This multicenter retrospective study included acute ischemic stroke patients who received intravenous urokinase or alteplase from January 2014 to January 2018 at 21 centers in China. Outcomes and treatment complications were analyzed by univariate and multivariate analyses. Results: Among the 618 patients included in this study, 489 were treated with urokinase and 129 were treated with alteplase. Functional independence, no/minimal disability, mortality, intracranial hemorrhage (ICH), and symptomatic ICH did not significantly differ between the urokinase and alteplase groups in the univariate and multivariate analyses. However, the patients who received alteplase had a lower odds ratio (OR) of extracranial bleeding in the univariate analysis and a lower adjusted OR (aOR) in the multivariate analysis than the patients who received urokinase (OR = 0.410 [95% CI, 0.172-0.977], p = 0.038; aOR = 0.350 [95% CI, 0.144-0.854], p = 0.021). Furthermore, in patients treated with urokinase, the patients who received high-dose urokinase had a higher OR of extracranial bleeding in the univariate analysis and a higher aOR of extracranial bleeding in the multivariate analysis than patients who received low-dose urokinase (OR = 3.046 [95% CI, 1.696-5.470], p < 0.001; aOR = 3.074 [95% CI, 1.627-5.807], p = 0.001). Moreover, patients who received low-dose urokinase had similar outcomes and complications compared to patients treated with alteplase. Conclusions: Patients treated with urokinase had similar outcomes but a higher risk of extracranial bleeding compared to patients treated with alteplase. The risk of extracranial bleeding was higher in the patients treated with high-dose urokinase than in the patients treated with low-dose urokinase. Patients who received low-dose urokinase had similar outcomes and complications compared to patients treated with alteplase. In countries such as China where some acute ischemic stroke patients cannot afford alteplase, urokinase may be a good alternative to alteplase for intravenous thrombolysis.

SUBMITTER: Zhang R

PROVIDER: S-EPMC8311518 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceThe benefit of intravenous thrombolysis (IVT) for acute ischemic stroke declines with longer time from symptom onset, but it is not known whether a similar time dependency exists for IVT followed by thrombectomy.ObjectiveTo determine whether the benefit associated with IVT plus thrombectomy vs thrombectomy alone decreases with treatment time from symptom onset.Design, setting, and participantsIndividual participant data meta-analysis from 6 randomized clinical trials comparing IVT plus thrombectomy vs thrombectomy alone. Enrollment was between January 2017 and July 2021 at 190 sites in 15 countries. All participants were eligible for IVT and thrombectomy and presented directly at thrombectomy-capable stroke centers (n = 2334). For this meta-analysis, only patients with an anterior circulation large-vessel occlusion were included (n = 2313).ExposureInterval from stroke symptom onset to expected administration of IVT and treatment with IVT plus thrombectomy vs thrombectomy alone.Main outcomes and measuresThe primary outcome analysis tested whether the association between the allocated treatment (IVT plus thrombectomy vs thrombectomy alone) and disability at 90 days (7-level modified Rankin Scale [mRS] score range, 0 [no symptoms] to 6 [death]; minimal clinically important difference for the rates of mRS scores of 0-2: 1.3%) varied with times from symptom onset to expected administration of IVT.ResultsIn 2313 participants (1160 in IVT plus thrombectomy group vs 1153 in thrombectomy alone group; median age, 71 [IQR, 62 to 78] years; 44.3% were female), the median time from symptom onset to expected administration of IVT was 2 hours 28 minutes (IQR, 1 hour 46 minutes to 3 hours 17 minutes). There was a statistically significant interaction between the time from symptom onset to expected administration of IVT and the association of allocated treatment with functional outcomes (ratio of adjusted common odds ratio [OR] per 1-hour delay, 0.84 [95% CI, 0.72 to 0.97], P = .02 for interaction). The benefit of IVT plus thrombectomy decreased with longer times from symptom onset to expected administration of IVT (adjusted common OR for a 1-step mRS score shift toward improvement, 1.49 [95% CI, 1.13 to 1.96] at 1 hour, 1.25 [95% CI, 1.04 to 1.49] at 2 hours, and 1.04 [95% CI, 0.88 to 1.23] at 3 hours). For a mRS score of 0, 1, or 2, the predicted absolute risk difference was 9% (95% CI, 3% to 16%) at 1 hour, 5% (95% CI, 1% to 9%) at 2 hours, and 1% (95% CI, -3% to 5%) at 3 hours. After 2 hours 20 minutes, the benefit associated with IVT plus thrombectomy was not statistically significant and the point estimate crossed the null association at 3 hours 14 minutes.Conclusions and relevanceIn patients presenting at thrombectomy-capable stroke centers, the benefit associated with IVT plus thrombectomy vs thrombectomy alone was time dependent and statistically significant only if the time from symptom onset to expected administration of IVT was short.

Project description:In-hospital delay reduces the benefit of intravenous thrombolysis (IVT) in acute ischemic stroke (AIS), while factors affecting in-hospital delay are less well known in Chinese. We are aiming at determining the specific factors associated with in-hospital delay through a hospital based cohort. In-hospital delay was defined as door-to-needle time (DTN) ≥60 min (standard delay criteria) or ≥75% percentile of all DTNs (severe delay criteria). Demographic data, time intervals [onset-to-door time (OTD), DTN, door-to-examination time (DTE), door-to-imaging time (DTI), door-to-laboratory time (DTL) and final-test-to-needle time (FTN, the time interval between the time obtaining the result of the last screening test and the needle time)], medical history and additional variables were calculated using Mann-Whitney U or Pearson Chi-Square tests for group comparison, and multivariate linear regression analysis was performed to identify independent variables of in-hospital delay. A total of 202 IVT cases were enrolled. The median age was 61 years and 25.2% were female. The cutoff points for the upper quartile of DTN (severe delay criteria) was 135 min.When compared with the reference group without in-hospital delay, older age, shorter OTD and less referral were found in the standard delay group and male sex, presence with transient ischemic attacks or rapidly improving symptom, and with multi-model CT imaging were more frequent in the severe delay group. In the multivariate linear regression analysis, FTN (P<0.001) and DTL (P = 0.002) were significantly associated with standard delay; while DTE (P = 0.005), DTI (P = 0.033), DTL (P<0.001), and FTN (P<0.001) were positively associated with severe delay. There was not a significant change in the trend of DTNs during the study period (P = 0.054). In-hospital delay was due to multifactors in China, in which time delays of decision-making process and laboratory tests contributed the most. Efforts aiming at reducing the delay should be focused on the optimization for the items of screening tests and improvement of the pathway organization.

Project description:We aimed to compare the safety and efficacy of intravenous thrombolysis (IVT) with alteplase for anterior circulation stroke (ACS) and posterior circulation stroke (PCS). From a large multicenter prospective registry-the Thrombolysis Implementation and Monitor of Acute Ischemic Stroke in China database-all patients who received IVT within 4.5?hours after stroke onset was reviewed. According to the clinical presentations and imaging findings, the eligible patients were divided into ACS and PCS groups. The safety and efficacy outcome measures included post-IVT symptomatic intracranial hemorrhage (sICH), parenchymal hematoma, and all intracranial hemorrhage (aICH) within 7 days, mortality within 90 days, excellent recovery (modified Rankin Scale 0-1), and functional independence (modified Rankin Scale 0-2) at 90 days. For comparing the outcomes between both groups, the odds ratios (ORs) with 95% confidence intervals (CIs) and the adjusted ORs with 95% CIs were analyzed by univariate and multivariate logistic regression models. Of 953 patients enrolled, 829 patients had ACS and 124 had PCS. The patients with PCS had less often atrial fibrillation (11.3% vs 19.8%; P = 0.02), higher blood glucose level (8.31 vs 7.63?mmol/L; P = 0.02), and more white blood cell counts (8.79 vs 7.75?×?10/L; P = 0.001) than those with ACS. After adjustment for the potential confounders, multivariate logistic analysis showed that PCS patients had not only lower rates of sICH (3.2% vs 7.7%; OR 0.28, 95% CI 0.09-0.90), parenchymal hematoma (1.6% vs 9.2%; OR 0.13, 95% CI 0.03-0.57), and aICH (8.1% vs 20.4%; OR 0.26, 95% CI 0.12-0.54), but also higher proportions of excellent recovery (55.7% vs 41.6%; OR 2.27, 95% CI 1.42-3.61) and functional independence (63.9% vs 53.0%; OR 2.33, 95% CI 1.40-3.89) compared with ACS patients. However, there was no significant difference in the occurrence of mortality (OR 0.86, 95% CI 0.39-1.91) between both groups in the multivariate model, although more PCS patients seemed to die within 90 days than did ACS patients (15.6% vs 10.1%; OR 1.64, 95% CI 0.96-2.82) in the univariate analysis. Our study suggests that IVT with alteplase is more safe and effective for PCS.

Project description:BackgroundThe stroke screening survey (SSS) is an essential strategy for stroke prevention. However, previous studies rarely discussed the effect of SSS on the acute phase treatment procedure for acute ischemic stroke (AIS) and the long-term prognosis outcomes. This study aims to investigate the effect of SSS on intravenous thrombolysis and long-term outcomes in AIS patients.MethodsThe stroke patients included were collected from Jiading Residences Community Health Records and Shanghai Stroke Service System database, from January 2017 to December 2019. Patients were divided into two groups, according to whether they have been screened before the event (onset and death). Demographic characteristics and treatment information of patients in the two groups were compared by the Mann-Whitney test and Chi-square test. The demographic differences between groups were adjusted with Propensity Score Matching (PSM) to evaluate the effect of SSS on door-to-needle time (DNT). The Kaplan-Meier survival curve with a log-rank test and multiple Cox regression model were used to evaluate the effect of SSS on long-term lifetime.ResultsA total of 1,236 patients with AIS were collected, including 468 (37.86%) female, 126 (10.19%) patients with intravenous thrombolysis, 241 (23.30%) patients died from all-cause mortality by January 8, 2020. A total of 124 (10.03%) patients have been screened before AIS onset, and 261 (21.17%) patients had undergone SSS after AIS onset. The baseline information indicated that patients with previous screening were older than the patients without at the time of onset [75 (70, 83) vs. 73 (65, 82), P=0.017], as well as more likely to have a history of hypertension (90.32% vs. 78.51%, P=0.002) and diabetes (50.00% vs. 25.81%, P<0.001). PSM results showed that patients with previous screening were associated with less severe onset situation [3 (1, 9) vs. 3 (1, 5), P=0.001] and shorter DNT [30 (24, 49) vs. 44 (31.5, 49), P=0.037] when compared to patients without. Additionally, patients with SSS had a lower hazard ratio of 0.567 (95% CI: 0.380-0.847, P=0.006) on all-cause mortality.ConclusionsFor AIS patients, the SSS is associated with less severe onset situation, shorter DNT, and longer long-term lifetime.

Project description:BackgroundRates of thrombolysis in most countries are well below best practice benchmarks. We aimed to investigate thrombolysis utilization and its associated factors in acute ischemic stroke (AIS) patients in Hubei province, China, to assess neurologists' experiences of the treatment, and to identify barriers against the treatment from perspective of AIS patients and neurologists.MethodsSurvey of 2096 AIS patients and 709 neurologists from 66 hospitals was conducted in Hubei province between 2014 and 2015. A multivariable logistic regression model was utilized to identify the factors associated with thrombolysis utilization and neurologists' experiences with thrombolysis.ResultsOf the 2096 AIS patients, only 3.8% received thrombolysis. Of the 709 neurologists, 66.0% reported using thrombolysis for AIS patients. The main reasons for not using thrombolysis were late arrival of patients, fear of the risk of complications of thrombolysis, and light or quickly recovered stroke symptoms. The behavior and clinical characteristics of patients, including early admission to hospital (odds ratio [OR] = 5.81, 95% confidence intervals [CI] 3.31-10.20), using emergency medical services to be hospitalized (OR = 3.36, 95% CI 2.00-5.62), stroke history (OR = 0.53, 95% CI 0.28-0.99), and National Institute of Health Stroke Scale score < 4 (OR = 0.46, 95% CI 0.27-0.77) were shown to significantly affect the thrombolysis utilization in the multivariate model. In addition, hospital grade (OR = 2.84, 95% CI 1.84-4.37), education level (OR = 2.49, 95% CI 1.09-5.73), and working years (OR = 1.88, 95% CI 1.18-3.00) were strongly associated with neurologists' experiences of thrombolysis.ConclusionsA very low proportion of AIS patients received thrombolysis in Hubei province, China. Considerable education programs and interventions were required regarding knowledge of stroke treatment for clinicians and proper behavior after stroke for AIS patients and their families.

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Outcomes and Treatment Complications of Intravenous Urokinase Thrombolysis in Acute Ischemic Stroke in China.

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