Low-Versus Standard-Dose Alteplase for Ischemic Strokes Within 4.5 Hours: A Comparative Effectiveness and Safety Study

Beom Joon Kim, Moon Ku Han, Tai Hwan Park, Sang Soon Park, Kyung Bok Lee, Byung Chul Lee, Kyung Ho Yu, Mi Sun Oh, Jae Kwan Cha, Dae Hyun Kim, Jun Lee, Soo Joo Lee, Youngchai Ko, Jong Moo Park, Kyusik Kang, Yong Jin Cho, Keun Sik Hong, Joon Tae Kim, Jay Chol Choi, Dong Eog KimDong Ick Shin, Wook Joo Kim, Juneyoung Lee, Ji Sung Lee, Byung Woo Yoon, Philip B. Gorelick, Hee Joon Bae

Research output: Contribution to journalArticlepeer-review

56 Citations (Scopus)


Background and Purpose - The low-dose (0.6 mg/kg) alteplase strategy to treat acute ischemic stroke patients became widespread in East Asian countries, without rigorous testing against standard-dose (0.9 mg/kg) alteplase treatment. Our aim was to investigate the comparative effectiveness and safety of the low-dose versus standard-dose intravenous alteplase strategy. Methods - A total of 1526 acute ischemic stroke patients who qualified for intravenous alteplase and treated within 4.5 hours were identified from a prospective, multicenter, and nationwide stroke registry database. Primary outcomes were a modified Rankin scale score of 0 to 1 at 3 months after stroke and occurrence of symptomatic hemorrhagic transformation. Inverse probability of low-dose alteplase weighting by propensity scores was used to remove baseline imbalances between the 2 groups, and variation among centers were also accounted using generalized linear mixed models with a random intercept. Results - Low-dose intravenous alteplase was given to 450 patients (29.5%) and standard-dose intravenous alteplase to 1076 patients (70.5%). Low-dose alteplase treatment was comparable to standard-dose therapy according to the following adjusted outcomes and odds ratios (95% confidence intervals): modified Rankin scale score 0 to 1 at 3 months and 0.95 (0.68-1.32); modified Rankin scale 0 to 2 at 3 months and 0.84 (0.62-1.15); symptomatic hemorrhagic transformation and 1.05 (0.65-1.70); and 3-month mortality and 0.54 (0.35-0.83). The associations were unchanged when the analysis was limited to those without endovascular recanalization. Conclusions - The low-dose alteplase strategy was comparable to the standard-dose treatment in terms of the effectiveness and safety.

Original languageEnglish
Pages (from-to)2541-2548
Number of pages8
Issue number9
Publication statusPublished - 2015 Sept 28
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2015 American Heart Association, Inc.


  • acute ischemic stroke
  • hemorrhage
  • low-dose tPA
  • thrombolysis
  • tissue-type plasminogen activator

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialised Nursing


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