Abstract T P48: Intravenous Thrombolysis Using Low-Dose Alteplase for Nonagenarians with Acute Ischemic Stroke: The SAMURAI rtPA Registry

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Mikito Hayakawa ◽  
Masatoshi Koga ◽  
Shoichiro Sato ◽  
Shoji Arihiro ◽  
Yoshiaki Shiokawa ◽  
...  

Objective: Although intravenous thrombolysis (IVT) using alteplase for octogenarians with acute ischemic stroke becomes relatively familiar, it is unclear whether IVT for nonagenarians is a futile intervention. The purpose of this study is to clarify the efficacy and safety of IVT using low-dose alteplase (0.6 mg/kg) for nonagenarians compared with octogenarians. Methods: Stroke Acute Management with Urgent Risk-factor Assessment and Improvement (SAMURAI) rtPA registry retrospectively collected 600 consecutive acute stroke patients receiving IVT from 10 Japanese stroke centers between October 2005 and July 2008. We extracted all octogenarians (O group) and nonagenarians (N group) from the registry. We compared baseline characteristics, symptomatic intracranial hemorrhage (SICH), and 3-month outcomes between the groups. 3-month outcomes include; functional independence (FI) defined as a mRS score 0-2, good outcome (GO) as a mRS score 0-2 or same as the premorbid mRS, poor outcome (PO) defined as a mRS score 5-6, and death. Results: Twenty-five nonagenarians (mean age, 93 years) and 124 octogenarians (mean age, 84 years) were included. N group was more female-predominant (76% versus 56%, p=0.06) and premorbidly dependent (44% versus 14%, p<0.001) than O group. There were no significant differences of median baseline NIHSS score (16 versus 14, p=0.95) and Alberta Stroke Program Early CT Score (9 versus 9, p=0.36) between the groups. The rate of FI tended to be lower in N group than O group (16% versus 36%, p=0.06), otherwise, the differences of the rates of GO (28% versus 37%, p=0.39), PO (40% versus 36%, p=0.73), death (20% versus 11%, p=0.23) and SICH (0% versus 2.4%, p=1.00) were not significant between the groups. In comparison with O group, N group was not associated with 3-month clinical outcomes (FI; OR 0.61; 95% CI, 0.15-2.42, GO; 0.98; 0.31-3.07, PO; 0.63; 0.15-2.70, death; 3.18; 0.62-16.3) and SICH (0.68; 0.17-2.69) after multivariate adjustment. Conclusions: IVT using low-dose alteplase for N group resulted in less frequent achievement of FI mainly because of more premorbid dependency than O group, however, showed at least a similar safety and a potential efficacy.

2017 ◽  
Vol 79 (1-2) ◽  
pp. 68-73 ◽  
Author(s):  
Guangjian Zhao ◽  
Tingfen Huang ◽  
Mei Zheng ◽  
Yansen Cui ◽  
Yunyong Liu ◽  
...  

Objective: This study analyzed the efficacy and safety of low-dose and standard-dose alteplase intravenous thrombolytic therapy for acute ischemic stroke (AIS). Methods: Patients with AIS who underwent intravenous alteplase thrombolysis from July 2012 to December 2016 were retrospectively analyzed and correspondingly divided into low-dose (0.6–0.89 mg/kg) group and standard-dose group (0.9 mg/kg) according to alteplase dosage. The clinical outcome was evaluated by modified Rankin Scale (mRS) at 90 days after onset. The safety index was the mortality at 90 days after onset and the incidence of symptomatic intracranial hemorrhage (SICH) within 7 days. Results: A total of 1,486 patients were included (1,115 cases in low-dose group and 371 cases in standard-dose group). There were no significant differences in baseline data between the 2 groups. As mRS, good outcome rate as well as mortality rate in both groups had no significant difference (36.1 vs. 37.6%; χ2 = 10.882, p = 0.890; 5.5 vs. 7.3%; χ2 = 2.163, p = 0.076), but the incidence of SICH in low-dose group was significantly lower than that of the standard-dose group (2.2 vs. 5.9%; χ2 = 3.157, p = 0.001). Conclusion: The efficacy of low-dose alteplase intravenous thrombolytic therapy for AIS was equivalent to the standard-dose regimen but with higher safety.


2021 ◽  
pp. neurintsurg-2021-017667
Author(s):  
Chun-Hsien Lin ◽  
Jeffrey L Saver ◽  
Bruce Ovbiagele ◽  
Wen-Yi Huang ◽  
Meng Lee

ObjectiveTo conduct a meta-analysis of randomized trials to comprehensively compare the effect of endovascular thrombectomy (EVT) versus intravenous thrombolysis (IVT) plus EVT on functional independence (modified Rankin Scale (mRS) 0–2) after acute ischemic stroke due to large vessel occlusions (AIS-LVO).MethodsWe searched Pubmed, EMBASE, CENTRAL, and clinicaltrials.gov from January 2000 to February 2021 and abstracts presented at the International Stroke Conference in March 2021 to identify trials comparing EVT alone versus IVT plus EVT in AIS-LVO. Five non-inferiority margins established in the literature were assessed: −15%, −10%, −6.5%, −5%, and −1.3% for the risk difference for functional independence at 90 days.ResultsFour trials met the selection criteria, enrolling 1633 individuals, with 817 participants randomly assigned to EVT alone and 816 to IVT plus EVT. Crude cumulative rates of 90-day functional independence were 46.0% with EVT alone versus 45.5% with IVT plus EVT. Pooled results showed the risk difference of functional independence was 1% (95% CI −4% to 5%) between EVT alone versus IVT plus EVT. The lower 95% CI bound of −4% fell within the non-inferiority margins of −15%, −10%, −6.5%, and −5%, but not −1.3%. Pooled results also showed the risk difference between EVT alone versus IVT plus EVT was 1% (95% CI −3% to 5%) for mRS 0–1, and 1% (95% CI −1% to 3%) for symptomatic intracranial hemorrhage.ConclusionsThis meta-analysis suggests that EVT alone is non-inferior to IVT plus EVT for several, but not the most stringent, non-inferiority margins.


2021 ◽  
Vol 12 ◽  
Author(s):  
Gaoting Ma ◽  
Shuo Li ◽  
Baixue Jia ◽  
Dapeng Mo ◽  
Ning Ma ◽  
...  

Purpose: Tirofiban administration to acute ischemic stroke patients undergoing mechanical thrombectomy with preceding intravenous thrombolysis remains controversial. The aim of the current study was to evaluate the safety and efficacy of low-dose tirofiban during mechanical thrombectomy in patients with preceding intravenous thrombolysis.Methods: Patients with acute ischemic stroke undergoing mechanical thrombectomy and preceding intravenous thrombolysis were derived from “ANGEL-ACT,” a multicenter, prospective registry study. The patients were dichotomized into tirofiban and non-tirofiban groups based on whether tirofiban was administered. Propensity score matching was used to minimize case bias. The primary safety endpoint was symptomatic intracerebral hemorrhage (sICH), defined as an intracerebral hemorrhage (ICH) associated with clinical deterioration as determined by the Heidelberg Bleeding Classification. All ICHs and hemorrhage types were recorded. Clinical outcomes included successful recanalization, dramatic clinical improvement, functional independence, and mortality at the 3-month follow-up timepoint. Successful recanalization was defined as a modified Thrombolysis in Cerebral Ischemia score of 2b or 3. Dramatic clinical improvement at 24 h was defined as a reduction in NIH stroke score of ≥10 points compared with admission, or a score ≤1. Functional independence was defined as a Modified Rankin Scale (mRS) score of 0–2 at 3-months.Results: The study included 201 patients, 81 in the tirofiban group and 120 in the non-tirofiban group, and each group included 68 patients after propensity score matching. Of the 201 patients, 52 (25.9%) suffered ICH, 15 (7.5%) suffered sICH, and 18 (9.0%) died within 3-months. The median mRS was 3 (0–4), 99 (49.3%) achieved functional independence. There were no statistically significant differences in safety outcomes, efficacy outcomes on successful recanalization, dramatic clinical improvement, or 3-month mRS between the tirofiban and non-tirofiban groups (all p &gt; 0.05). Similar results were obtained after propensity score matching.Conclusion: In acute ischemic stroke patients who underwent mechanical thrombectomy and preceding intravenous thrombolysis, low-dose tirofiban was not associated with increased risk of sICH or ICH. Further randomized clinical trials are needed to confirm the effects of tirofiban in patients undergoing bridging therapy.


BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yunzhen Hu ◽  
Chunmei Ji

Abstract Background The efficacy and safety of intravenous thrombolysis (IVT) for acute ischemic stroke with atrial fibrillation (AF) is still controversial. Methods We conducted a meta-analysis of all relevant studies, retrieved through systematic search of PubMed, Embase, and Cochrane databases up to December 31, 2019. Modified Rankin Scale (mRS) scores of 0–1 at 90 days, mRS of 0–2 at 90 days, overall mortality, and incidence of symptomatic intracranial hemorrhage (sICH) were collected as outcome measures. Fixed- and random-effects meta-analytical models were applied, and between-study heterogeneity was assessed. Results A total of 8509 patients were enrolled in 18 studies. A comparison of IVT treatment in AF versus non-AF patients showed that AF was associated with a significantly lower proportion of patients with mRS of 0–1 (24.1% vs. 34.5%; OR 0.59; 95% CI 0.43–0.81; P < 0.001), mRS of 0–2 (33.6% vs. 47.8%; OR 0.55; 95% CI 0.43–0.70; P < 0.001), as well as significantly higher mortality (19.4% vs. 11.5%; OR 2.05; 95% CI 1.79–2.36; P < 0.001) and higher incidence of sICH (6.4% vs. 4.1%; OR 1.60; 95% CI 1.27–2.01; P < 0.001). A comparison of AF patients who were subjected or not to IVT showed that thrombolysis carried a higher risk of sICH (5.7% vs. 1.6%; OR 3.44; 95% CI 2.04–5.82; P < 0.001) and was not associated with a better prognosis. Subgroup analysis in prospective studies also suggested a poorer functional prognosis and higher mortality in AF patients treated with IVT compared with those who did not receive IVT. Some heterogeneity was present in this meta-analysis. Conclusions Acute IS patients with AF had worse outcomes than those without AF after thrombolytic therapy, and had a higher incidence of sICH after thrombolysis than those without thrombolysis. Thrombolysis in ischemic stroke patients with AF should be carefully considered based on clinical factors such as NIHSS score, age, and the type of AF.


2020 ◽  
Author(s):  
Yunzhen Hu ◽  
Chunmei Ji

Abstract Background The efficacy and safety of intravenous thrombolysis (IVT) in acute ischemic stroke with atrial fibrillation (AF) were controversial. Methods We performed a meta-analysis of all relevant studies retrieved by systematic searches of the, Embase, and Cochrane databases up to December 31, 2019. Modified Rankin Scale (mRS) scores 0–1 at 90 days, mRS 0–2 at 90 days, overall mortality, and symptomatic intracranial hemorrhage (sICH) incidence were collected as outcome measures. Fixed effects meta-analytical models were used, and between-study heterogeneity was assessed. Results A total of 8,509 patients were enrolled in eighteen studies. In AF IVT versus non-AF IVT studies, AF was associated with a significant decrease in the proportion of patients with mRS of 0–1 (24.1% vs. 34.5%; OR 0.57; 95% CI 0.50–0.65; P = 0.000), mRS of 0–2 (33.6% vs. 47.8%; OR 0.50; 95% CI 0.44–0.57; P = 0.000) and significant higher in mortality (19.4% vs. 11.5%; OR 2.05; 95% CI 1.79–2.36; P = 0.000) and sICH incidence (6.4% vs. 4.1%; OR 1.60; 95% CI 1.27–2.01; P = 0.000). In AF IVT versus AF non-IVT studies, thrombolysis carried a higher risk of sICH (5.7% vs. 1.6%; OR 3.44; 95% CI 2.04–5.82; P = 0.000) instead of a better prognosis. Subgroup analysis in prospective studies also suggested a poorer functional prognosis and higher mortality in AF patients treated IVT compared with non-IVT. Conclusion Patients with AF had worse outcomes than those without AF after thrombolytic therapy. Patients with AF had a higher incidence of sICH after thrombolysis than those without thrombolysis.


2021 ◽  
Vol 12 ◽  
Author(s):  
Sheng-Feng Lin ◽  
Han-Hwa Hu ◽  
Bo-Lin Ho ◽  
Chih-Hung Chen ◽  
Lung Chan ◽  
...  

Background: This study aimed to investigate the safety and efficacy of single antiplatelet, anticoagulant and Dual Antiplatelet pre-treatment (DAPP) in older, moderate to high severity acute ischemic stroke patients treated with intravenous thrombolysis (IVT).Methods: A prospective cohort study was conducted to monitor the development of symptomatic intracranial hemorrhage (SICH) and functional outcomes at 90 days. Two different dosages of alteplase were used for IVT. Logistic regression models were used for analysis of the safety and efficacy outcomes.Results: A total of 1,156 patients were enrolled and categorized into six groups based on their pre-treatment medications: (1) aspirin (n = 213), (2) clopidogrel (n = 37), (3) DAPP of aspirin + clopidogrel (n= 27), (4) warfarin (n = 44), (5) any of the above pre-medications (n = 331), and (6) none of these medications as controls (n = 825). The DAPP group showed significantly increased SICH by the NINDS (adjusted OR: 4.90, 95% CI 1.28–18.69) and the ECASS II (adjusted OR: 5.09, 95% CI: 1.01–25.68) standards. The aspirin group was found to significantly improve the favorable functional outcome of the modified Rankin Scale (mRS) of 0–1 (adjusted OR: 1.91, 95% CI, 1.31.2.78), but no significance for mRS of 0–2 (adjusted OR: 1.39, 95% CI, 0.97–1.99). The DAPP group also significantly increased mortality (adjusted OR: 4.75, 95% CI: 1.77–12.72). A significant interaction between different dosages for IVT and the functional status was noted. Compared to standard dose, the DAPP group showed higher proportions of disability and mortality with low dose of IVT.Conclusion: For older adults with higher baseline severity of acute ischemic stroke, DAPP may increase the risk of SICH and mortality post IVT. However, DAPP is still not an indication to withdraw IVT and to prescribe low-dose IVT for older adults.


2020 ◽  
Vol 17 ◽  
Author(s):  
Jie Chen ◽  
Fu-Liang Zhang ◽  
Shan Lv ◽  
Hang Jin ◽  
Yun Luo ◽  
...  

Objective:: Increased leukocyte count are positively associated with poor outcomes and all-cause mortality in coronary heart disease, cancer, and ischemic stroke. The role of leukocyte count in acute ischemic stroke (AIS) remains important. We aimed to investigate the association between admission leukocyte count before thrombolysis with recombinant tissue plasminogen activator (rt-PA) and 3-month outcomes in AIS patients. Methods:: This retrospective study included consecutive AIS patients who received intravenous (IV) rt-PA within 4.5 h of symptom onset between January 2016 and December 2018. We assessed outcomes including short-term hemorrhagic transformation (HT), 3-month mortality, and functional independence (modified Rankin Scale [mRS] score of 0–2 or 0–1). Results:: Among 579 patients who received IV rt-PA, 77 (13.3%) exhibited HT at 24 h, 43 (7.4%) died within 3 months, and 211 (36.4%) exhibited functional independence (mRS score: 0–2). Multivariable logistic regression revealed admission leukocyte count as an independent predictor of good and excellent outcomes at 3 months. Each 1-point increase in admission leukocyte count increased the odds of poor outcomes at 3 months by 7.6% (mRS score: 3–6, odds ratio (OR): 1.076, 95% confidence interval (CI): 1.003–1.154, p=0.041) and 7.8% (mRS score: 2–6, OR: 1.078, 95% CI: 1.006–1.154, p=0.033). Multivariable regression analysis revealed no association between HT and 3-month mortality. Admission neutrophil and lymphocyte count were not associated with 3-month functional outcomes or 3-month mortality. Conclusion:: Lower admission leukocyte count independently predicts good and excellent outcomes at 3 months in AIS patients undergoing rt-PA treatment.


2020 ◽  
Vol 10 (3) ◽  
pp. 148-158
Author(s):  
Yu Cui ◽  
Zhong-He Zhou ◽  
Xiao-Wen Hou ◽  
Hui-Sheng Chen

<b><i>Introduction:</i></b> The delipid extracorporeal lipoprotein filter from plasma (DELP) has been approved for the treatment of acute ischemic stroke (AIS) by the China Food and Drug Administration, but its effectiveness and mechanism are not yet fully determined. The purpose of this study was to evaluate the effect of DELP treatment on AIS patients after intravenous thrombolysis. <b><i>Methods:</i></b> A retrospective study was performed on AIS patients with no improvement within 24 h after intravenous thrombolysis who were subsequently treated with or without DELP. Primary outcome was the proportion with a modified Rankin scale (mRS) of 0–1 at 90 days. Secondary outcomes were changes in National Institute of Health Stroke Scale (NIHSS) score from 24 h to 14 days after thrombolysis, and the rate of improvement in stroke-associated pneumonia (SAP). The main safety outcomes were the rates of symptomatic intracranial hemorrhage and mortality. To investigate its mechanisms, serum biomarkers were measured before and after DELP. <b><i>Results:</i></b> A total of 252 patients were recruited, 63 in the DELP group and 189 matched patients in the NO DELP group. Compared with the NO DELP group, the DELP group showed an increase in the proportion of mRS 0–1 at 90 days (<i>p</i> = 0.042). More decrease in NIHSS from 24 h to 14 days (<i>p</i> = 0.024), a higher rate of improvement in SAP (<i>p</i> = 0.022), and lower mortality (<i>p</i> = 0.040) were shown in DELP group. Furthermore, DELP decreased levels of interleukin (IL)-1β, E-selectin, malondialdehyde, matrix metalloprotein 9, total cholesterol, low-density lipoprotein, and fibrinogen, and increased superoxide dismutase (<i>p</i>&#x3c; 0.05). <b><i>Conclusions:</i></b> DELP following intravenous thrombolysis should be safe, and is associated with neurological function improvement, possibly through multiple neuroprotective mechanisms. Prospective trials are needed.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Giovanni Merlino ◽  
Carmelo Smeralda ◽  
Gian Luigi Gigli ◽  
Simone Lorenzut ◽  
Sara Pez ◽  
...  

AbstractTo date, very few studies focused their attention on efficacy and safety of recanalisation therapy in acute ischemic stroke (AIS) patients with cancer, reporting conflicting results. We retrospectively analysed data from our database of consecutive patients admitted to the Udine University Hospital with AIS that were treated with recanalisation therapy, i.e. intravenous thrombolysis (IVT), mechanical thrombectomy (MT), and bridging therapy, from January 2015 to December 2019. We compared 3-month dependency, 3-month mortality, and symptomatic intracranial haemorrhage (SICH) occurrence of patients with active cancer (AC) and remote cancer (RC) with that of patients without cancer (WC) undergoing recanalisation therapy for AIS. Patients were followed up for 3 months. Among the 613 AIS patients included in the study, 79 patients (12.9%) had either AC (n = 46; 7.5%) or RC (n = 33; 5.4%). Although AC patients, when treated with IVT, had a significantly increased risk of 3-month mortality [odds ratio (OR) 6.97, 95% confidence interval (CI) 2.42–20.07, p = 0.001] than WC patients, stroke-related deaths did not differ between AC and WC patients (30% vs. 28.8%, p = 0.939). There were no significant differences between AC and WC patients, when treated with MT ± IVT, regarding 3-month dependency, 3-month mortality and SICH. Functional independence, mortality, and SICH were similar between RC and WC patients. In conclusion, recanalisation therapy might be used in AIS patients with nonmetastatic AC and with RC. Further studies are needed to explore the outcome of AIS patients with metastatic cancer undergoing recanalisation therapy.


2021 ◽  
Vol 19 ◽  
Author(s):  
Xiaohua Xie ◽  
Jie Yang ◽  
Lijie Ren ◽  
Shiyu Hu ◽  
Wancheng Lian ◽  
...  

Background: Symptomatic intracranial hemorrhage (sICH) is a serious hemorrhagic complication after intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients. Most existing predictive scoring systems were derived from Western countries Objective: To develop a nomogram to predict the possibility of sICH after IVT in an Asian population. Methods: This retrospective cohort study included AIS patients treated with recombinant tissue plasminogen activator (rt-PA) in a tertiary hospital in Shenzhen, China, from January 2014 to December 2020. The end point was sICH within 36 hours of IVT treatment. Multivariable logistic regression was used to identify risk factors of sICH, and a predictive nomogram was developed. Area under the curve of receiver operating characteristic curves (AUC), calibration curve, and decision curve analyses were performed. The nomogram was validated by bootstrap resampling Results: Data on a total of 462 patients were collected, of whom 20 patients (4.3%) developed sICH. In the multivariate logistic regression model, the National Institute of Health stroke scale scores (NIHSS) (odds ratio [OR], 1.14; 95% confidence interval [CI], 1.06–1.23, P < 0.001), onset to treatment time (OTT) (OR, 1.02; 95% CI, 1.01–1.03, P < 0.001), neutrophil to lymphocyte ratio (NLR) (OR, 1.22; 95% CI, 1.09–1.35, P < 0.001), and cardioembolism (OR, 3.74; 95% CI, 1.23–11.39, P = 0.020) were independent predictors for sICH and were used to construct a nomogram. Our nomogram exhibited favorable discrimination ability [AUC, 0.878; specificity, 87.35%; and sensitivity, 73.81%]. Bootstrapping for 500 repetitions was performed to further validate the nomogram. The AUC of the bootstrap model was 0.877 (95% CI: 0.823–0.922). The calibration curve exhibited good fit and calibration. The decision curve revealed good positive net benefits and clinical effects Conclusion: The nomogram consisted of the predictors NIHSS, OTT, NLR, and cardioembolism could be used as an auxiliary tool to predict the individual risk of sICH in Chinese AIS patients after IVT. Further external verification among more diverse patient populations is needed to demonstrate the accuracy of the model’s predictions.


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