Effect of Argatroban Plus Intravenous Alteplase vs Intravenous Alteplase Alone on Neurologic Function in Patients with Acute Ischemic Stroke: The ARAIS Randomized Clinical Trial

Overview

Background

Previous studies suggested the benefit of argatroban plus alteplase (recombinant tissue-type plasminogen activator) in patients with acute ischemic stroke (AIS). However, strong evidence in trials with large sample sizes is missing. The objective of this study is to assess the efficacy of argatroban plus alteplase for acute ischemic stroke.

Methods

  • This multicenter, open-label, blinded endpoint randomized clinical trial included 808 patients with acute ischemic stroke.
  • Eligible patients were randomly assigned within 4.5 hours of the symptom onset to the argatroban plus alteplase group (n=402), which received intravenous argatroban within 1 hour after alteplase, or alteplase alone group (n=415) which received intravenous alteplase alone.
  • Both groups received guideline-based treatments. 

Results

  • Among 817 patients with acute ischemic stroke who were randomized (median age, 65 years, 238 women) completed the trial.
  • At 90 days, 210 of 329 participants in the argatroban plus alteplase group versus 238 of 367 in the alteplase alone group had an excellent functional outcome.
  • The percentages of participants with symptomatic intracranial hemorrhage, parenchymal hematoma type 2, and major systemic bleeding were 2.1%, 2.3%, and 0.3% in the argatroban plus alteplase group and 1.8%, 2.5%, and 0.5% in the alteplase alone group.

Conclusion

Among patients with acute ischemic stroke treatment with argatroban plus intravenous alteplase compared with alteplase alone did not result in a significantly greater likelihood of excellent functional outcome at 90 days.

Adapted from:

  1. Chen HS, Cui Y, Zhou ZH, Dai YJ, Li GH, Peng ZL, Zhang Y, Liu XD, Yuan ZM, Jiang CH, Yang QC, Duan YJ, Ma GB, Zhao LW, Wang RX, Sun YL, Shen L, Wang EQ, Wang LH, Feng YF, Wang FY, Zou RL, Yang HP, Wang K, Wang DL, Wang YL; ARAIS Investigators. Effect of Argatroban Plus Intravenous Alteplase vs Intravenous Alteplase Alone on Neurologic Function in Patients with Acute Ischemic Stroke: The ARAIS Randomized Clinical Trial. JAMA. 2023 Feb 28;329(8):640-650. doi: 10.1001/jama.2023.0550. PMID: 36757755; PMCID: PMC9912168