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

J Stroke Cerebrovasc Dis. 2018 Apr;27(4):988-997. doi: 10.1016/j.jstrokecerebrovasdis.2017.11.005. Epub 2017 Dec 7.

Abstract

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.

Keywords: Tissue plasminogen activator; dose; efficacy; safety; stroke.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Aged
  • Aged, 80 and over
  • Asian People
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / ethnology
  • Brain Ischemia / mortality
  • Chi-Square Distribution
  • Disability Evaluation
  • Female
  • Fibrinolytic Agents / administration & dosage*
  • Fibrinolytic Agents / adverse effects
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Odds Ratio
  • Randomized Controlled Trials as Topic
  • Recovery of Function
  • Risk Factors
  • Stroke / drug therapy*
  • Stroke / ethnology
  • Stroke / mortality
  • Thrombolytic Therapy / adverse effects
  • Thrombolytic Therapy / methods*
  • Thrombolytic Therapy / mortality
  • Time Factors
  • Tissue Plasminogen Activator / administration & dosage*
  • Tissue Plasminogen Activator / adverse effects
  • Treatment Outcome

Substances

  • Fibrinolytic Agents
  • Tissue Plasminogen Activator