Current status of intravenous tissue plasminogen activator dosage for acute ischaemic stroke: an updated systematic review

Stroke Vasc Neurol. 2018 Jan 13;3(1):28-33. doi: 10.1136/svn-2017-000112. eCollection 2018 Mar.

Abstract

The optimal dose of recombinant tissue plasminogen activator (rtPA) for acute ischaemic stroke (AIS) remains controversial, especially in Asian countries. We aimed to update the evidence regarding the use of low-dose versus standard-dose rtPA. We performed a systematic literature search across MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PsycINFO and Cumulative Index to Nursing and Allied Health Literature (CINAHL) from inception to 22 August 2016 to identify all related studies. The outcomes were death or disability (defined by modified Rankin Scale 2-6), death, and symptomatic intracerebral haemorrhage (sICH). Where possible, data were pooled for meta-analysis with ORs and corresponding 95% CIs by means of random-effects or fixed-effects meta-analysis. We included 26 observational studies and 1 randomised controlled trial with a total of 23 210 patients. Variable doses of rtPA were used for thrombolysis of AIS in Asia. Meta-analysis shows that low-dose rtPA was not associated with increased risk of death or disability (OR 1.13, 95% CI 0.95 to 1.33), or death (OR 0.86, 95% CI 0.74 to 1.01), or decreased risk of sICH (OR 1.06, 95% CI 0.65 to 1.72). The results remained consistent when sensitivity analyses were performed including only low-dose and standard-dose rtPA or only Asian studies. Our review shows small difference between the outcomes or the risk profile in the studies using low-dose and/or standard-dose rtPA for AIS. Low-dose rtPA was not associated with lower risk of death or disability, death alone, or sICH.

Keywords: Asian; acute ischemic stroke; low-dose tissue plasminogen activator; thrombolysis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cerebral Hemorrhage / chemically induced
  • Female
  • Fibrinolytic Agents / administration & dosage*
  • Fibrinolytic Agents / adverse effects
  • Functional Status
  • Humans
  • Infusions, Intravenous
  • Ischemic Stroke / diagnosis
  • Ischemic Stroke / drug therapy*
  • Ischemic Stroke / mortality
  • Ischemic Stroke / physiopathology
  • Male
  • Middle Aged
  • Observational Studies as Topic
  • Recombinant Proteins / administration & dosage
  • Recovery of Function
  • Risk Assessment
  • Risk Factors
  • Severity of Illness Index
  • Thrombolytic Therapy* / adverse effects
  • Thrombolytic Therapy* / mortality
  • Tissue Plasminogen Activator / administration & dosage*
  • Tissue Plasminogen Activator / adverse effects
  • Treatment Outcome

Substances

  • Fibrinolytic Agents
  • Recombinant Proteins
  • Tissue Plasminogen Activator