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.