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

• DOI: 10.1161/strokeaha.115.010180
• Publication Date: 2015-08-05T02:20:21Z
• Authors: 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 Kim; Dong-Ick Shin; Wook-Joo Kim; Juneyoung Lee; Ji Sung Lee; Byung-Woo Yoon; Philip B. Gorelick; Hee-Joon Bae
• Keywords: Aged, 80 and over; Male; Middle Aged; Severity of Illness Index; Brain Ischemia; 3. Good health; Stroke; 03 medical and health sciences; 0302 clinical medicine; Fibrinolytic Agents; Tissue Plasminogen Activator; Outcome Assessment, Health Care; Humans; Female; Thrombolytic Therapy; Registries; Aged

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.