Efficacy of argatroban plus alteplase according to time from onset to thrombolysis in acute ischemic stroke: a prespecified

Background: The Argatroban Plus Recombinant Tissue-Type Plasminogen Activator for AIS (ARAIS) trial failed to demonstrate the benefit of argatroban in patients diagnosed with acute ischemic stroke who were treated with intravenous alteplase. A Methods: The included patients were classified into two subgroups according to OTT. The primary outcome was an excellent functional outcome at 90 days, defined as a modified Rankin Scale score of 0 or 1. The efficacy of argatroban plus alteplase was investigated in each subgroup compared with alteplase alone. Results: Overall, 696 patients were included: 452 were assigned to the OTT < 180 min subgroup, and 244 to the OTT ≥ 180 min subgroup. The treatment effect of argatroban plus alteplase was similar to that of alteplase alone in the OTT < 180 min subgroup (adjusted RD [95% CI] = 0.5% [-5.6 to 6.6%]) and OTT ≥ 180 min subgroup (adjusted RD [95% CI] = -1.3% [-9.8 to 7.1%]). No significant interaction between the treatment efficacy and OTT was found ( Interpretation: The prespecified secondary analysis indicated that the efficacy of argatroban plus alteplase did not differ according to OTT in terms of achieving 90-day excellent functional outcomes compared with alteplase alone. Trial registration: ClinicalTrials.gov, Identifier: NCT03740958.