Safety and Efficacy of Repeated Thrombolysis with Alteplase in Early Recurrent Ischemic Stroke: A Systematic Review

J Stroke Cerebrovasc Dis. 2019 Oct;28(10):104290. doi: 10.1016/j.jstrokecerebrovasdis.2019.07.006. Epub 2019 Jul 29.

Abstract

Background and aim: The current American Heart Association guidelines for the management of acute ischemic stroke advise against the use of intravenous (IV) alteplase in patients with recurrent stroke occurring within 90 days of their index event. Following these guidelines strictly, patients having early recurrent ischemic stroke would be unable to avail of this reperfusion strategy that has been proven to confer superior clinical outcomes. While some registry-based studies have demonstrated the safety of IV alteplase in this subgroup of patients, data on the repeated use of the drug are lacking. Thus, we aim to determine the safety and efficacy of repeated thrombolysis in patients with early recurrent ischemic strokes.

Methods: The following electronic databases were searched for relevant studies: the Cochrane Central Register for Controlled Trials by The Cochrane Library, MEDLINE by PubMed, Health Research and Development Information Network, Scopus, and ClinicalTrials.gov. Data on symptomatic intracranial hemorrhage, 90-day clinical outcomes, systemic hemorrhage and allergic reactionswere synthesized.

Results: Ten articles with 33 patients in total were included in our review. One patient developed symptomatic intracranial hemorrhage after the second reperfusion attempt and subsequently died from pneumonia. Another died from spontaneous rupture of previously unidentified infrarenal aortic aneurysm. Six of the 13 patients with available follow-up data had good clinical outcomes (Modified Rankin Score 0-2). There were no allergic reactions and other drug-related adverse events noted.

Conclusions: Repeated IV alteplase can be safe and efficacious in patients who have early recurrent ischemic stroke. Larger studies, trials, or registry-based data are needed to ascertain the encouraging findings of our review.

Keywords: Ischemic stroke—recurrence—thrombolysis—off label use—recombinant tissue-type plasminogen activator—alteplase.

Publication types

  • Systematic Review

MeSH terms

  • Administration, Intravenous
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / mortality
  • Fibrinolytic Agents / administration & dosage*
  • Fibrinolytic Agents / adverse effects
  • Humans
  • Recurrence
  • Retreatment
  • Risk Factors
  • Stroke / drug therapy*
  • Stroke / mortality
  • Thrombolytic Therapy* / adverse effects
  • Thrombolytic Therapy* / mortality
  • Time Factors
  • Tissue Plasminogen Activator / administration & dosage*
  • Tissue Plasminogen Activator / adverse effects
  • Treatment Outcome

Substances

  • Fibrinolytic Agents
  • Tissue Plasminogen Activator