Standard-Dose Intravenous Tissue-Type Plasminogen Activator for Stroke Is Better Than Low Doses

Abstract

Background and Purpose-It remains uncertain whether lower dose intravenous tissue-type plasminogen activator (tPA) for stroke is as effective and safe as the standard dose. Methods-We analyzed data from the Thrombolysis Implementation and Monitor of Acute Ischemic Stroke in China (TIMSChina). Patients who were treated within 4.5 hours after symptom onset were included. These patients were divided into 5 groups according to tPA doses given: <0.5, 0.5 to 0.7, 0.7 to 0.85, 0.85 to 0.95, and ≥0.95 mg/kg. Symptomatic intracranial hemorrhage, mortality, and 90-day outcome assessed by modified Rankin scale were analyzed. Results-A total of 919 patients were enrolled. Among them, 9 had <0.5 mg/kg, 75 had 0.5 to 0.7 mg/kg, 131 had 0.

Low-Versus Standard-Dose Alteplase for Ischemic Strokes Within 4.5 Hours

“…[8][9][10][11][12] The efficacy of the low-dose alteplase strategy has been challenged, however, based on a lack of concomitant controls and 2 recent publications from Mainland China and Taiwan, suggesting contrary conclusions in relation to the efficacy of low-dose alteplase. 13,14 Also, the advent of efficacious and safe endovascular devices and prior use of IV thrombolysis further highlights the need for a safe and effective alteplase strategy. [15][16][17] In the absence of a large-scale clinical trial, observational data from a large clinical registry can be useful for assessing alternative treatment strategies.…”

“…Recently, 2 reports from Chinese studies addressed the pitfalls by analyzing fairly large registry data. 13,14 However, both of the studies did not include prespecified doses of IV alteplase, and variation in the dose of alteplase among centers and patients was substantial. The analyses were subject to casual post hoc grouping of alteplase doses, and thus, it is difficult to draw any conclusions based on proper comparison.…”

Low-Dose versus Standard-Dose Intravenous Alteplase in Acute Ischemic Stroke

“…[1][2][3] However, the Japanese drug safety authority has approved the use of alteplase at a dose of 0.6 mg per kilogram after an uncontrolled, open-label study showed that this dose resulted in equivalent clinical outcomes and a lower risk of intracerebral hemorrhage than that reported in published studies in which the 0.9-mg-per-kilogram dose was used. 4 Other registry studies in Asia [5][6][7][8][9][10][11] have shown inconsistent results, but a high risk of symptomatic intracerebral hemorrhage was observed among Asian patients treated with 0.9 mg of alteplase per kilogram in the United States. 12 Differing perceived risks of intracerebral hemorrhage and treatment affordability have led to variations in the doses of intravenous alteplase used to treat patients with acute ischemic stroke in Asia.…”

“…12 Differing perceived risks of intracerebral hemorrhage and treatment affordability have led to variations in the doses of intravenous alteplase used to treat patients with acute ischemic stroke in Asia. [8][9][10][11] The Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED) was designed to compare low-dose with standard-dose intravenous alteplase in patients with acute ischemic stroke. Using a quasi-factorial design, we are also assessing the effects of early intensive lowering of blood pressure as compared with guideline-recommended management in patients with elevated blood pressure; this part of the trial is scheduled to be completed in 2018.…”

Low- Versus Standard-Dose Alteplase in Patients on Prior Antiplatelet Therapy

“…Concerns of a higher risk of sICH have led to a wide range of doses of intravenous alteplase being used in many Asian countries in relation to perceived risks and affordability of the treatment. 9 Although 3 studies-2 registries 14,15 and 1 observational 16 -have specifically evaluated outcomes by dose of alteplase in Asian populations, only Chao et al 16 reported a trend toward an adverse effect of prior APT on outcome. In particular, use of clopidogrel or ticlopidine, but not aspirin, was associated with an increased risk of sICH on multivariate analysis.…”