Low-Dose Tissue Plasminogen Activator and Standard-Dose Tissue Plasminogen Activator in Acute Ischemic Stroke in Asian Populations: A Review (original) (raw)
Related papers
2014
I n America and Europe, the current recommended dose of recombinant tissue-type plasminogen activator (r-tPA) for acute ischemic stroke is 0.9 mg/kg, but a similar study with this dosage has never been replicated in a controlled trial in East Asia. A lower dose (0.6 mg/kg) of r-tPA was used in Japan and was proved to have similar outcomes compared with a dose of 0.9 mg/kg in Western countries. 1,2 However, the Safe Implementation of Thrombolysis in Stroke-Non-European Union World (SITS-NEW) study demonstrated that the safety and efficacy of the dose of 0.9 mg/kg of r-tPA in an Asian population was similar to those of the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) study in the European population. 3,4 Our previous study, the Taiwan Thrombolytic Therapy for Acute Ischemic Stroke (TTT-AIS) study, was the first to determine whether the thrombolytic therapy in routine clinical use was as safe and effective in Chinese patients as in white patients. 5 The preliminary results showed that the group receiving a dose of 0.9 mg/kg had higher rates of symptomatic intracerebral hemorrhage (SICH), dependence, and mortality within 3 months than the low-dose group (<0.85 mg/kg). This finding was more prominent in older patients aged ≥70 years. Background and Purpose-The relationship between the dose of recombinant tissue-type plasminogen activator (r-tPA) and its safety/efficacy for ischemic stroke has not been well evaluated in the East Asian population. We assessed the safety/efficacy of different doses of r-tPA for acute ischemic stroke in Chinese patients. Methods-A total of 1004 eligible patients were classified according to the dose of r-tPA received for managing acute ischemic stroke: 0.9 mg/kg (n=422), 0.8 mg/kg (n=202), 0.7 mg/kg (n=199), and 0.6 mg/kg (n=181). The safety outcome was symptomatic intracerebral hemorrhage and death within 3 months. The efficacy outcome was good functional outcome (modified Rankin Scale ≤1) at 3 months. Results-There was a significant trend for symptomatic intracerebral hemorrhage with age (P=0.002). With multivariate logistic regression analysis, a dose of 0.9 mg/kg was a predictor of symptomatic intracerebral hemorrhage (P=0.0109), and a dose ≤0.65 mg/kg was a predictor of good functional outcome (P=0.0369). In patients aged 71 to 80 years, there was a significant trend of increasing symptomatic intracerebral hemorrhage (P=0.0130) and less good functional outcome (P=0.0179) with increasing doses of r-tPA. There was also a trend of increasing mortality (P=0.0971) at 3 months in these patients. Conclusions-These results did not support the dose of 0.9 mg/kg of r-tPA being optimal for all patients in the East Asian population. In elderly patients (71-80 years), a lower dose of 0.6 mg/kg is associated with a better outcome. Confirmation of the results through randomized trial is required.
The Outcome of Treatment With Recombinant Tissue Plasminogen Activator in Acute Ischemic Stroke
Background: Thrombolytic therapy is the recommended treatment of acute ischemic stroke. It is crucial to evaluate the treatment results with recombinant Tissue Plasminogen Activator (r-TPA) in patients with acute stroke. Objectives: This study aimed to evaluate treatment outcomes with r-TPA in patients with acute stroke in a referral stroke center in Iran. Materials & Methods: In this retrospective study, 87 patients with symptoms of acute stroke were examined. They were referred to a stroke center in Gilan Province, Iran, from June 2016 to April 2020 and received r-TPA (0.9 mg/kg). Demographic information, the time interval between the onset of symptoms and r-TPA administration, complications, and National Institutes of Health Stroke Scale (NIHSS) upon arrival and discharge and death of patients were extracted from their hospital files. The paired t-test, independent t-test, and Pearson correlation test were used to compare variables using IBM SPSS for Windows version 20.0 (IBM Corp., Armonk, NY, USA). Results: The Mean±SD of NIHSS reduced from 14.7±6.4 to 8.9±7.6 (P<0.001). The most common complication was Intracerebral Hemorrhage (ICH) (12.6%). The hospital mortality rate was 23%. ICH occurred among 40% (n=8) of those who expired, and 4.47% (n=3) of them survived, and this difference was significant (P<0.001). Conclusion: The recovery with r-TPA administration in the stroke center was acceptable. Mortality and ICH occurrence rates were higher than other non-Iranian studies. It seems that we should change the case selection criteria and prescription dose to achieve better results of treatment with TPA.
Journal of stroke, 2015
In a recent pooled analysis of randomized clinical trials (RCTs), intravenous tissue plasminogen activator (TPA) improves the outcome in patients aged ≥80 years. However, it is uncertain whether the findings are applicable to clinical practice in Asian populations. From a multicenter stroke registry database of Korea, we identified patients with acute ischemic stroke who were aged ≥ 80 years. Using multivariable analysis and propensity score (PS)-matched analyses, we assessed the effectiveness and safety of intravenous TPA within 4.5 hours. Among 2,334 patients who met the eligible criteria, 236 were treated with intravenous TPA (mean age, 83±5; median NIHSS, 13 [IQR, 8-17]). At discharge, the TPA group compared to the no-TPA group had a favorable shift on the modified Rankin Scale (mRS) score (multivariable analysis, OR [95% CI], 1.51 [1.17-1.96], P=0.002; PS-matched analysis, 1.54 [1.17-2.04], P=0.002) and was more likely to achieve mRS 0-1 outcome (multivariable analysis, 2.00 [1...
Annals of vascular surgery, 2010
Local intra-arterial thrombolysis (LIT) has been previously suggested as an effective therapy for acute ischemic stroke. In this study, we describe our experience of using LIT for the treatment of Taiwanese patients with ischemic stroke at different vascular locations, before and after Alteplase was approved as a first-line treatment in Taiwan. The criteria required for the initiation of LIT have become more stringent after the approval of Alteplase (AA). A retrospective analysis of medical records was conducted for 20 ischemic stroke patients treated with LIT; including 10 patients treated before and 10 patients treated after AA (we did not treat any of the patients in this study with AA). Urokinase was used for LIT treatment. Outcome measures included patient demographics, clinical characteristics, and clinical outcomes before and after LIT. Clinical outcomes were evaluated using four different stroke scales. The median National Institutes of Health stroke scale score (NIHSS) befo...
Lancet, 2012
Thrombolysis is of net benefit in patients with acute ischaemic stroke, who are younger than 80 years of age and are treated within 4·5 h of onset. The third International Stroke Trial (IST-3) sought to determine whether a wider range of patients might benefit up to 6 h from stroke onset. In this international, multicentre, randomised, open-treatment trial, patients were allocated to 0·9 mg/kg intravenous recombinant tissue plasminogen activator (rt-PA) or to control. The primary analysis was of the proportion of patients alive and independent, as defined by an Oxford Handicap Score (OHS) of 0-2 at 6 months. The study is registered, ISRCTN25765518. 3035 patients were enrolled by 156 hospitals in 12 countries. All of these patients were included in the analyses (1515 in the rt-PA group vs 1520 in the control group), of whom 1617 (53%) were older than 80 years of age. At 6 months, 554 (37%) patients in the rt-PA group versus 534 (35%) in the control group were alive and independent (O...
Acta neurologica Belgica, 2007
The short time window is frequently cited as the main reason for exclusion of intravenous tissue plasminogen activator (tPA) in acute stroke. Identifying and circumventing barriers to thrombolysis other than time could increase the frequency of treatment. The goal of this study was to identify whether the rate of treatment with tPA would increase if time window was not an obstacle to treatment. In four hospitals we prospectively recorded the rate of tPA use in consecutive patients admitted with acute ischemic stroke and in those admitted within 3 hours, the reasons why thrombolysis was not given, and the potential gain in the rate of tPA use if all patients had been admitted within 3 hours considering all exclusion criteria other than time. We recruited 486 patients (258 men; mean age, 70.4 +/- 13.5 years), of whom 154 (31.7%) were admitted within 3 hours. The time of stroke onset was unknown in 28 (5.8%). The rate of tPA use was 11.1% in the whole study population and 35.1% in thos...
Stroke, 2004
Background and Purpose-Acute ischemic stroke patients are infrequently treated with recombinant tissue plasminogen activator (rtPA). We present unique population-based data regarding the eligibility of ischemic stroke patients for rtPA treatment. Methods-All ischemic strokes presenting to an emergency department (ED) within a biracial population of 1.3 million were identified. The patient was considered eligible for rtPA on the basis of exclusion criteria from the National Institute of Neurological Disorders and Stroke rtPA trial. Results-Of 2308 ischemic strokes, 1849 presented to an ED. Only 22% of all ischemic strokes in the population arrived in the ED in Ͻ3 hours from symptom onset; of these, 209 (51%) were ineligible for rtPA on the basis of mild stroke severity, medical and surgical history, or blood tests.
Tissue Plasminogen Activator for Acute Ischemic Stroke in Clinical Practice
2003
Background and Purpose—Concerns persist regarding the safety of tissue plasminogen activator (tPA) therapy for acute ischemic stroke. Numerous case series of clinical experience with tPA have been published that provide additional data on the safety of thrombolytic therapy. Methods—This is a meta-analysis of 15 published, open-label studies that broadly followed approved indications and guidelines for tPA use in nonselective patient populations. Results—In 2639 treated patients, the symptomatic intracerebral hemorrhage rate was 5.2% (95% confidence interval, 4.3 to 6.0), slightly lower than the 6.4% rate in the treated group of the randomized, placebo-controlled National Institute of Neurological Disorders and Stroke (NINDS) trial. The mean total death rate (13.4%) and proportion of subjects achieving a very favorable outcome (37.1%) were comparable to the NINDS trial results. Protocol deviations were reported in 19.8%. Comparing across studies showed that the mortality rate was cor...