Low- versus Standard-Dose Intravenous Tissue-Type Plasminogen Activator for Acute Ischemic Stroke: An Updated Meta-Analysis

Background We performed a meta-analysis to compare the efficacy and safety between low- and standard-dose intravenous (IV) tissue-type plasminogen activator (tPA) for acute ischemic stroke (AIS) patients within 4.5 hours of symptom onset. Methods We searched PubMed and EMBASE for relevant studies from inception to June1, 2017. Cohort or randomized controlled studies for AIS within 4.5 hours of symptom onset with comparison between low-dose and standard-dose tPA were included. The primary efficacy end point was favorable functional outcome (modified Rankin scale scores [mRS] of 0-1) at 90 days. The primary safety end point was the incidence rate of symptomatic intracerebral hemorrhage (sICH). The secondary end points were independent functional outcome (mRS scores of 0-2) and mortality. Results A total of 11 studies were pooled in this meta-analysis. The low-dose strategy appeared to be as effective as standard-dose tPA (43.4% versus 45.4%; odds ratio [OR] = 0.93, 95% confidence interval [CI]: 0.78-1.10; P = .38) in primary efficacy outcome. The secondary efficacy outcome produced similar results (57.3% versus 57.0%; OR = 0.95, 95% CI: 0.86-1.05; P = .33). There was no evidence of statistical difference for sICH (4.2% versus 4.9%; OR = 1.02 [0.66-1.55]; P = .94) and mortality (9.0% versus 10.6%; OR = 0.99 [0.74-1.31]; P = .92) at 90 days between low- and standard-dose therapy. In a subgroup analysis by ethnicity, there was no significant difference between patients of Asian and non-Asian descent for any of the end points. Conclusions This study showed that AIS patients receiving low-dose IV-tPA had comparably efficacy and safety to those receiving standard-dose IV-tPA. However, the effect is especially pronounced within the Asian population, which limits the generalizability of these results. We performed a meta-analysis to compare the efficacy and safety between low- and standard-dose intravenous (IV) tissue-type plasminogen activator (tPA) for acute ischemic stroke (AIS) patients within 4.5 hours of symptom onset. We searched PubMed and EMBASE for relevant studies from inception to June1, 2017. Cohort or randomized controlled studies for AIS within 4.5 hours of symptom onset with comparison between low-dose and standard-dose tPA were included. The primary efficacy end point was favorable functional outcome (modified Rankin scale scores [mRS] of 0-1) at 90 days. The primary safety end point was the incidence rate of symptomatic intracerebral hemorrhage (sICH). The secondary end points were independent functional outcome (mRS scores of 0-2) and mortality. A total of 11 studies were pooled in this meta-analysis. The low-dose strategy appeared to be as effective as standard-dose tPA (43.4% versus 45.4%; odds ratio [OR] = 0.93, 95% confidence interval [CI]: 0.78-1.10; P = .38) in primary efficacy outcome. The secondary efficacy outcome produced similar results (57.3% versus 57.0%; OR = 0.95, 95% CI: 0.86-1.05; P = .33). There was no evidence of statistical difference for sICH (4.2% versus 4.9%; OR = 1.02 [0.66-1.55]; P = .94) and mortality (9.0% versus 10.6%; OR = 0.99 [0.74-1.31]; P = .92) at 90 days between low- and standard-dose therapy. In a subgroup analysis by ethnicity, there was no significant difference between patients of Asian and non-Asian descent for any of the end points. This study showed that AIS patients receiving low-dose IV-tPA had comparably efficacy and safety to those receiving standard-dose IV-tPA. However, the effect is especially pronounced within the Asian population, which limits the generalizability of these results.