Low-dose intravenous tissue plasminogen activator for acute ischaemic stroke: an alternative or a new standard?

Background: With the recent publication of a large clinical trial on the use of a lower dose of intravenous (IV) tissue plasminogen activator (tPA) for acute ischaemic stroke (AIS), the concept of using a different dose has been debated. We intend to review the literature on using a lower dose of IV tPA and gain a better understanding of the impact of different IV doses on the treatment of patients with AIS. Methods: A comprehensive literature search of the related topics in PubMed, EMBASE, Web of Science and MEDLINE was carried out. Key words used include low dose IV tPA, thrombolysis, Alteplace and tPA for AIS. Findings were tabulated according to the size of the cohort studied, outcome, adverse event and level of evidence. The results of all studies using lower doses were analysed for efficacy and adverse events. Results: From 1992 to 2016, there were 23 trials that included 10950 patients published on the use of lower doses of IV tPA for AIS. Doses ranged from 0.5, 0.6, 0.75 to 0.85 mg/kg. Most were observational, retrospective and registry studies. One was a prospective open-label randomised controlled trial. 13 trials combined lower doses of IV tPA with a glycoprotein IIb/IIIa inhibitor or thrombectomy. Patients treated with lower doses of IV tPA showed a trend of lower rate of symptomatic intracranial haemorrhage and mortality at 3 months but slightly more disability. Conclusions: Lower doses of IV tPA showed less haemorrhagic events but were not more effective compared with the standard dose. The optimal low dose of IV tPA remains unclear. Patients with AIS with a high risk of developing sypmtomatic intracranial haemorrhage might benefit from lower dose IV tPA, such as 0.6 mg/kg.