Effectiveness of intravenous r-tPA versus UK for acute ischaemic stroke: a nationwide prospective Chinese registry study.
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ABSTRACT: Background
Intravenous recombinant tissue plasminogen activator (r-tPA) and urokinase (UK) are both recommended for the treatment of acute ischaemic stroke (AIS) in China, but with few comparative outcome data being available. We aimed to compare the outcomes of these two thrombolytic agents for the treatment of patients within 4.5 hours of onset of AIS in routine clinical practice in China.Methods
A pre-planned, prospective, nationwide, multicentre, real-world registry of consecutive patients with AIS (age ≥18 years) who received r-tPA or UK within 4.5 hours of symptom onset according to local decision-making and guideline recommendations during 2017-2019. The primary effectiveness outcome was the proportion of patients with an excellent functional outcome (defined by modified Rankin scale scores 0 to 1) at 90 days. The key safety endpoint was symptomatic intracranial haemorrhage according to standard definitions. Multivariable logistic regression was used for comparative analysis, with adjustment according to propensity scores to ensure balance in baseline characteristics.Results
Overall, 4130 patients with AIS were registered but 320 had incomplete or missing data, leaving 3810 with available data for analysis of whom 2666 received r-tPA (median dose 0.88 (IQR 0.78-0.90) mg/kg) and 1144 received UK (1.71 (1.43-2.00)×104 international unit per kilogram). There were several significant intergroup differences in patient characteristics: r-tPA patients were more educated, had less history of stroke, lower systolic blood pressure, greater neurological impairment and shorter treatment times from symptom onset than UK patients. However, in adjusted analysis, the frequency of excellent outcome (OR 1.18, 95% CI 1.00 to 1.40, p=0.052) and symptomatic intracranial haemorrhage (OR 0.70, 95% CI 0.33 to 1.47, p=0.344) were similar between groups.Conclusions
UK may be as effective and carry a similar safety profile as r-tPA in treating mild to moderate AIS within guidelines in China. REGISTRATION: http://www.clinicaltrials.gov. unique identifier: NCT02854592.
SUBMITTER: Wang X
PROVIDER: S-EPMC8717806 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundMost ischaemic strokes are caused by blockage of a cerebral artery by a thrombus. Intravenous administration of recombinant tissue plasminogen activator given within 4.5 hours is now standard treatment for this condition. Percutaneous vascular interventions use an intra-arterial, mechanical approach for thrombus disruption or removal (thrombectomy). Recent randomised trials indicate that percutaneous vascular interventions are superior to usual care (usual care usually included intravenous thrombolysis). However, intravenous thrombolysis was usually given in both arms of the trial and there was a lack of direct comparison of percutaneous vascular interventions with intravenous thrombolysis.ObjectivesTo assess the effectiveness and safety of percutaneous vascular interventions compared with intravenous thrombolytic treatment for acute ischaemic stroke.Search methodsWe searched the Cochrane Stroke Group Trials Register (last search: August 2018). In addition, in September 2017, we searched the following electronic databases: CENTRAL, MEDLINE, Embase, and Science Citation Index; and Stroke Trials Registry, and US National Institutes of Health Ongoing Trials Register, ClinicalTrials.gov.Selection criteriaRandomised controlled trials (RCTs) that directly compared a percutaneous vascular intervention with intravenous thrombolytic treatment in people with acute ischaemic stroke.Data collection and analysisTwo review authors applied the inclusion criteria, extracted data, and assessed risk of bias. We obtained both published and unpublished data. We assessed the quality of the evidence using the GRADE approach.Main resultsWe included four trials with 450 participants. Data on functional outcome and death at end of follow-up were available for 443 participants from three trials. Compared with intravenous thrombolytic therapy, percutaneous vascular intervention did not improve the proportion of participants with good functional outcome (modified Rankin Scale score 0 to 2, risk ratio (RR) 1.01, 95% confidence interval (CI) 0.82 to 1.25, P = 0.92). The quality of evidence was low (outcome assessment was blinded, but not the treating physician or participants). At the end of follow-up, there was a non-significant increase in the proportion of participants who died in the percutaneous vascular intervention group (RR 1.34, 95% CI 0.84 to 2.14, P = 0.21). The quality of evidence was low (wide confidence interval). There was no difference in the proportion of participants with symptomatic intracranial haemorrhages between the intervention and control groups (RR 0.99, 95% CI 0.50 to 1.95, P = 0.97). The quality of evidence was low (wide confidence interval). Data on vascular status (recanalisation rate) were only available for seven participants from one trial; we considered this inadequate for statistical analyses.Authors' conclusionsThe present review directly compared intravenous thrombolytic treatment with percutaneous vascular interventions for ischaemic stroke. We found no evidence from RCTs that percutaneous vascular interventions are superior to intravenous thrombolytic treatment with respect to functional outcome. Quality of evidence was low (outcome assessment was blinded, but not the treating physician or participants). New trials with adequate sample sizes are warranted because of the rapid development of new techniques and devices for such interventions.
| S-EPMC6516947 | biostudies-literature
Project description:Intravenous thrombolysis is the only approved systemic reperfusion treatment for patients with acute ischaemic stroke. These European Stroke Organisation (ESO) guidelines provide evidence-based recommendations to assist physicians in their clinical decisions with regard to intravenous thrombolysis for acute ischaemic stroke. These guidelines were developed based on the ESO standard operating procedure and followed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. The working group identified relevant clinical questions, performed systematic reviews and meta-analyses of the literature, assessed the quality of the available evidence, and wrote recommendations. Expert consensus statements were provided if not enough evidence was available to provide recommendations based on the GRADE approach. We found high quality evidence to recommend intravenous thrombolysis with alteplase to improve functional outcome in patients with acute ischemic stroke within 4.5 h after symptom onset. We also found high quality evidence to recommend intravenous thrombolysis with alteplase in patients with acute ischaemic stroke on awakening from sleep, who were last seen well more than 4.5 h earlier, who have MRI DWI-FLAIR mismatch, and for whom mechanical thrombectomy is not planned. These guidelines provide further recommendations regarding patient subgroups, late time windows, imaging selection strategies, relative and absolute contraindications to alteplase, and tenecteplase. Intravenous thrombolysis remains a cornerstone of acute stroke management. Appropriate patient selection and timely treatment are crucial. Further randomized controlled clinical trials are needed to inform clinical decision-making with regard to tenecteplase and the use of intravenous thrombolysis before mechanical thrombectomy in patients with large vessel occlusion.
| S-EPMC7995316 | biostudies-literature
Project description:IntroductionIn patients with stroke attributable to cervical artery dissection, we compared endovascular therapy to intravenous thrombolysis regarding three-month outcome, recanalisation and complications.Materials and methodsIn a multicentre intravenous thrombolysis/endovascular therapy-register-based cohort study, all consecutive cervical artery dissection patients with intracranial artery occlusion treated within 6?h were eligible for analysis. Endovascular therapy patients (with or without prior intravenous thrombolysis) were compared to intravenous thrombolysis patients regarding (i) excellent three-month outcome (modified Rankin Scale score 0-1), (ii) symptomatic intracranial haemorrhage, (iii) recanalisation of the occluded intracranial artery and (iv) death. Upon a systematic literature review, we performed a meta-analysis comparing endovascular therapy to intravenous thrombolysis in cervical artery dissection patients regarding three-month outcome using a random-effects Mantel-Haenszel model.ResultsAmong 62 cervical artery dissection patients (median age 48.8 years), 24 received intravenous thrombolysis and 38 received endovascular therapy. Excellent three-month outcome occurred in 23.7% endovascular therapy and 20.8% with intravenous thrombolysis patients. Symptomatic intracranial haemorrhage occurred solely among endovascular therapy patients (5/38 patients, 13.2%) while four (80%) of these patients had bridging therapy; 6/38 endovascular therapy and 0/24 intravenous thrombolysis patients died. Four of these 6 endovascular therapy patients had bridging therapy. Recanalisation was achieved in 84.2% endovascular therapy patients and 66.7% intravenous thrombolysis patients (odds ratio 3.2, 95% confidence interval [0.9-11.38]). Sensitivity analyses in a subgroup treated within 4.5?h revealed a higher recanalisation rate among endovascular therapy patients (odds ratio 3.87, 95% confidence interval [1.00-14.95]), but no change in the key clinical findings. In a meta-analysis across eight studies (n?=?212 patients), cervical artery dissection patients (110 intravenous thrombolysis and 102 endovascular therapy) showed identical odds for favourable outcome (odds ratio 0.97, 95% confidence interval [0.38-2.44]) among endovascular therapy patients and intravenous thrombolysis patients.Discussion and conclusionIn this cohort study, there was no clear signal of superiority of endovascular therapy over intravenous thrombolysis in cervical artery dissection patients, which - given the limitation of our sample size - does not prove that endovascular therapy in these patients cannot be superior in future studies. The observation that symptomatic intracranial haemorrhage and deaths in the endovascular therapy group occurred predominantly in bridging patients requires further investigation.
| S-EPMC6453244 | biostudies-literature
Project description:Blood-brain barrier (BBB) integrity injury within the thrombolytic time window is becoming a critical target to reduce haemorrhage transformation (HT). We have previously reported that BBB damage was initially damaged in non-infarcted striatum after acute ischaemia stroke. However, the underlying mechanism is not clear. Since acute ischaemic stroke could induce a significant increase of dopamine release in striatum, in current study, our aim is to investigate the role of dopamine receptor signal pathway in BBB integrity injury after acute ischaemia using rat middle cerebral artery occlusion model. Our data showed that 2-h ischaemia induced a significant increase of endogenous tissue plasminogen activator (tPA) in BBB injury area and intra-striatum infusion of tPA inhibitor neuroserpin, significantly alleviated 2-h ischaemia-induced BBB injury. In addition, intra-striatum infusion of D1 receptor antagonist SCH23390 significantly decreased ischaemia-induced upregulation of endogenous tPA, accompanied by decrease of BBB injury and occludin degradation. More important, inhibition of hypoxia-inducible factor-1 alpha with inhibitor YC-1 significantly decreased 2-h ischaemia-induced endogenous tPA upregulation and BBB injury. Taken together, our data demonstrate that acute ischaemia disrupted BBB through activation of endogenous tPA via HIF-1? upregulation, thus representing a new therapeutic target for protecting BBB after acute ischaemic stroke.
| S-EPMC7417722 | biostudies-literature
Project description:OBJECTIVE:The relationship of anticoagulation therapies with stroke severity and outcomes have been well documented in the literature. However, none of the previous research has reported the relationship of atrial fibrillation (AF)/anticoagulation therapies with urinary tract infection (UTI), pneumonia and length of stay in hyperacute stroke units (HASUs). The present study aimed to evaluate AF and anticoagulation status in relation to early outcomes in 1387 men (median age=75?years, IQR=65-83) and 1371 women (median age=83?years, IQR=74-89) admitted with acute ischaemic stroke to HASUs in Surrey between 2014 and 2016. METHODS:We conducted this registry-based, prospective cohort study using data from the Sentinel Stroke National Audit Programme. Association between AF anticoagulation status with severe stroke on arrival (National Institutes of Health Stroke Scale score ?16), prolonged HASU stay (>3?weeks), UTI and pneumonia within 7?days of admission, severe disability on discharge (modified Rankin Scale score=4?and 5) and inpatient mortality was assessed by logistic regression, adjusted for age, sex, hypertension, congestive heart failure, diabetes and previous stroke. RESULTS:Compared with patients with stroke who are free from AF, those with AF without anticoagulation had an increased adjusted risk of having more severe stroke: 5.8%?versus 14.0%, OR=2.4 (95%?CI 1.6 to 3.6, P<0.001), prolonged HASU stay: 21.5%?versus 32.0%, OR=1.4 (1.0-2.0, P=0.027), pneumonia: 8.2%?versus 19.1%, OR=2.1 (1.4-2.9, P<0.001), more severe disability: 24.2%?versus 40.4%, OR=1.6 (1.2-2.1, P=0.004) and mortality: 9.3%?versus 21.7%, OR=1.9 (1.4-2.8, P<0.001), and AF patients with anticoagulation also had greater risk for having UTI: 8.6%?versus 12.3%, OR=1.9 (1.2-3.0, P=0.004), pneumonia: 8.2%?versus 11.5%, OR=1.6 (1.1-2.4, P=0.025) and mortality: 9.7%?versus 21.7%, OR=1.9 (1.4-2.8, P<0.001). The median HASU stay for stroke patients with AF without anticoagulation was 10.6 days (IQR=2.8-26.4) compared with 5.8 days (IQR=2.3-17.5) for those free from AF (P<0.001). CONCLUSIONS:Patients with AF, particularly those without anticoagulation, are at increased risk of severe stroke, associated with prolonged HASU stay and increased risk of early infection, disability and mortality.
| S-EPMC5736041 | biostudies-literature
Project description:ObjectiveTo determine patient and hospital characteristics associated with not providing IV tissue plasminogen activator (tPA) to eligible patients with acute ischemic stroke (AIS) in clinical practice.MethodsWe performed a retrospective cohort study of patients with AIS arriving within 2 hours of onset to hospitals participating in Get With The Guidelines-Stroke without documented contraindications to IV tPA from April 2003 through December 2011, comparing those who received tPA to those who did not. Multivariable generalized estimating equation logistic regression modeling identified factors associated with not receiving tPA.ResultsOf 61,698 eligible patients with AIS presenting within 2 hours of onset (median age 73 years, 51% female, 74% non-Hispanic white, median NIH Stroke Scale score 11, interquartile range 6-18), 15,282 (25%) were not treated with tPA within 3 hours. Failure to give tPA decreased over time from 55% in 2003 to 2005 to 18% in 2010 to 2011 (p < 0.0001). After adjustment for all covariates, including stroke severity, factors associated with failure to treat included older age, female sex, nonwhite race, diabetes mellitus, prior stroke, atrial fibrillation, prosthetic heart valve, NIH Stroke Scale score <5, arrival off-hours and not via emergency medical services, longer onset-to-arrival and door-to-CT times, earlier calendar year, and arrival at rural, nonteaching, non-stroke center hospitals located in the South or Midwest.ConclusionsOverall, about one-quarter of eligible patients with AIS presenting within 2 hours of stroke onset failed to receive tPA treatment. Thrombolysis has improved dramatically over time and is strongly associated with stroke center certification. Additionally, some groups, including older patients, milder strokes, women, and minorities, may be undertreated.
| S-EPMC5067546 | biostudies-literature
Project description:Background and Purpose- Telemedicine is increasingly utilized for intravenous tPA (tissue-type plasminogen activator) delivery. The comparative safety of leaving tPA-treated patients at a presenting (spoke) hospital (drip-and-stay) or transferring patients to a central treating (hub) hospital (drip-and-ship) is not established. We sought to compare outcomes between drip-and-ship and drip-and-stay patients treated with tPA via telemedicine. We hypothesized that there would be no differences in short-term outcomes of in-hospital mortality, length of stay, or discharge disposition or in 90-day outcomes between groups. Methods- We retrospectively identified patients treated with tPA at 17 spoke hospitals between September 2015 and December 2016. Demographic, clinical, and outcome data were obtained from a prospective telemedicine registry. We used negative binomial, multinomial, and logistic regression analyses to evaluate length of stay, discharge disposition, and inpatient mortality, respectively. We compared the proportion of patients with 90-day modified Rankin Scale score <2 by group. Results- Among 430 tPA-treated patients, 232 (53.9%) were transferred to the hub after treatment. The median arrival National Institutes of Health Stroke Scale score was higher for drip-and-ship (10; interquartile range, 5-18) compared with drip-and-stay patients (6; interquartile range, 4-10; P<0.001). Unadjusted length of stay was longer in drip-and-stay patients (incidence rate ratio, 0.82; 95% CI, 0.71-0.95). There were no significant differences in adjusted length of stay, hospital mortality, or discharge disposition. Among the 64% of patients with complete 90-day modified Rankin Scale score, the proportion with good outcomes (modified Rankin Scale score <2) did not differ between groups. Conclusions- We found no differences in measured outcomes between drip-and-ship and drip-and-stay patients treated in our network, although our study may be underpowered to detect small differences.
| S-EPMC7384440 | biostudies-literature
Project description:Background and purposeWe aimed to determine whether young adults (<50 years) with acute ischaemic stroke (AIS) are more likely to receive intravenous tissue plasminogen activator (IV tPA) and have shorter time to treatment than older patients with stroke.MethodsWe analysed data from the Chinese Stroke Center Alliance registry for patients with AIS hospitalised between August 2015 and July 2019. Patients were classified into two groups according to age: young adults (<50 years of age) and older adults (≥50 years of age).ResultsOf 793 175 patients with AIS admitted to 1471 hospitals, 9.1% (71 860) were young adults. Compared with older adults, a higher proportion of young adults received IV tPA among patients without contraindicaitons (7.2% vs 6.1%, adjusted OR (aOR) 1.13, 95% CI 1.10 to 1.17) and among patients without contraindications and with onset-to-door time ≤3.5 hours (23.6% vs 19.3%, aOR 1.20, 95% CI 1.15 to 1.24). We did not observe differences in onset-to-needle time (median hours 2.7 hours) or door-to-needle time (DNT) (median minutes 60 min) between young and older adults. The proportion of DNT ≤30 min, DNT ≤45 min and DNT ≤60 min in young and older IV tPA-treated patients were 16.9% vs 18.8%, 30.2% vs 32.8% and 50.2% vs 54.2%, respectively. Compared with older adults, young adults treated with IV tPA had lower odds of in-hospital mortality (0.5% vs 1.3%, aOR 0.54, 95% CI 0.35 to 0.82) and higher odds of independent ambulation at discharge (61.0% vs 53.6%, aOR 1.15, 95% CI 1.08 to 1.22), and the associations may be partly explained by stroke severity measured by the National Institutes of Health Stroke Scale score.ConclusionYoung adults with AIS were more likely to receive IV tPA than older adults, although there was no difference between the two groups in time to treatment. Compared with older adults, young adults may had better in-hospital outcomes.
| S-EPMC9234794 | biostudies-literature
Project description:Background and Purpose- Although there are no trials or large cohorts to inform clinical care, current guidelines caution against giving intravenous tPA (tissue-type plasminogen activator) to patients with acute ischemic stroke who are taking non-vitamin K antagonist oral anticoagulants (NOACs). We performed a literature review of intravenous tPA in patients treated with NOACs preceding stroke. Methods- A literature search of PubMed was performed encompassing January 2010 to March 2018. Patient characteristics, timing of last medication intake, laboratory testing, use of reversal, and outcomes ?3 months after discharge were summarized. Results- We identified 55 studies with 492 NOAC patients receiving tPA (dabigatran, 181; rivaroxaban, 215; apixaban, 40; and unspecified NOAC, 56). Among patients with complete data, the median time from the last NOAC intake to symptom onset was 8 hours (interquartile range, 2.5-14.5), with 55.2% (80/145) within 12 hours. Few patients underwent sensitive laboratory tests, such as thrombin time, diluted thrombin time, or anti-Xa assays before tPA administration. The overall observed rates of symptomatic intracranial hemorrhage, mortality, and favorable outcomes (National Institutes of Health Stroke Scale score, ?1; modified Rankin Scale score, 0-2; or neurological improvement in the National Institutes of Health Stroke Scale score, ?8 points) were 4.3% (20/462), 11.3% (48/423), and 43.7% (164/375), respectively. Among dabigatran-treated patients, reversal with idarucizumab was associated with fewer symptomatic intracranial hemorrhage (4.5% [2/44] versus 7.4% [8/108]; unadjusted odds ratio, 0.60; 95% CI, 0.12-2.92), death (4.5% [2/44] versus 12.0% [13/108]; unadjusted odds ratio, 0.35; 95% CI, 0.08-1.61), and more favorable outcomes (79.1% [34/43] versus 39.2% [29/74]; unadjusted odds ratio, 5.86; 95% CI, 2.45-14.00), although the differences were not statistically significant for symptomatic intracranial hemorrhage and death. Conclusions- These preliminary observations suggest that tPA may be reasonably well tolerated without prohibitive risks of bleeding complications in selected patients on NOACs. Reversal of anticoagulant effects by idarucizumab for dabigatran-treated patients before tPA is an emerging strategy that was associated with more favorable outcomes.
| S-EPMC6706353 | biostudies-literature
Project description:BackgroundImatinib, a tyrosine kinase inhibitor, has been shown to restore blood-brain barrier integrity and reduce infarct size, haemorrhagic transformation and cerebral oedema in stroke models treated with tissue plasminogen activator. We evaluated the safety of imatinib, based on clinical and neuroradiological data, and its potential influence on neurological and functional outcomes.MethodsA phase II randomized trial was performed in patients with acute ischaemic stroke treated with intravenous thrombolysis. A total of 60 patients were randomly assigned to four groups [3 (active): 1 (control)]; the active treatment groups received oral imatinib for 6 days at three dose levels (400, 600 and 800 mg). Primary outcome was any adverse event; secondary outcomes were haemorrhagic transformation, cerebral oedema, neurological severity on the National Institutes of Health Stroke Scale (NIHSS) at 7 days and at 3 months and functional outcomes on the modified Rankin scale (mRS).ResultsFour serious adverse events were reported, which resulted in three deaths (one in the control group and two in the 400-mg dose group; one patient in the latter group did not receive active treatment and the other received two doses). Nonserious adverse events were mostly mild, resulting in full recovery. Imatinib ameliorated neurological outcomes with an improvement of 0.6 NIHSS points per 100 mg imatinib (P = 0.02). For the 800-mg group, the mean unadjusted and adjusted NIHSS improvements were 4 (P = 0.037) and 5 points (P = 0.012), respectively, versus controls. Functional independence (mRS 0-2) increased by 18% versus controls (61 vs. 79; P = 0.296).ConclusionThis phase II study showed that imatinib is safe and tolerable and may reduce neurological disability in patients treated with intravenous thrombolysis after ischaemic stroke. A confirmatory randomized trial is currently underway.
| S-EPMC5573589 | biostudies-literature