Different Doses of Recombinant Tissue-Type Plasminogen Activator for Acute Stroke in Chinese Patients

Abstract

In 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

High Plasma D-Dimer Indicates Unfavorable Outcome of Acute Ischemic Stroke Patients Receiving Intravenous Thrombolysis

“…Patients who provided blood samples for D-dimer level measurement after the initiation of rt-PA within 24 h after stroke onset were included. In our hospital, the therapeutic window of rt-PA was up to 4.5 h and the dose of rt-PA varied from 0.6 to 0.9 mg/kg depending on age [10] .…”

Management of Postthrombolysis Hemorrhagic and Orolingual Angioedema Complications

“…46,47 Additionally, the Taiwan Thrombolytic Therapy for Acute Ischemic Stroke (TTT-AIS) Study Group found the dose of 0.9 mg/kg of r-tPA to be suboptimal in Chinese patients with higher rates of SICH and found that in patients aged 71 to 80, a lower dose of 0.6 mg/kg was associated with better outcome. 44 These findings have not been confirmed through randomized controlled trials. The practice of administering lower doses of r-tPA for select high-risk patients is not followed in the United States.…”

“…1 There are some who propose the use of lower doses of r-tPA in populations at higher risk of ICH, such as East Asian populations, as a way to decrease the risk of bleeding. 43,44 For example in Japan, 0.6 mg/kg of r-tPA is the only approved dose since 2005 for acute stroke presenting within 3 hours of symptom onset, based on the results of the Japan Alteplase Clinical Trial (J-ACT) 45 and supported by J-ACT2 and the Japan post-Marketing Alteplase Registration Study (JMARS). 46,47 Additionally, the Taiwan Thrombolytic Therapy for Acute Ischemic Stroke (TTT-AIS) Study Group found the dose of 0.9 mg/kg of r-tPA to be suboptimal in Chinese patients with higher rates of SICH and found that in patients aged 71 to 80, a lower dose of 0.6 mg/kg was associated with better outcome.…”

The question of alteplase dose for stroke is not resolved

“…However, studies to determine the optimal dose of alteplase for Asian patients have produced conflicting findings. A study in Taiwan that included 1,004 patients who were treated with 0.6-0.9 mg/kg alteplase concluded that a lower dose was associated with a better outcome in patients aged 71-80 years 6 . Similarly, a multicentre registry study in South Korea that included 1,526 patients concluded that the effects of 0.6 mg/kg alteplase were comparable to those of 0.9 mg/ kg 7 .…”