OBJECTIVE: ARAIS trial failed to demonstrate benefit of argatroban as an adjunct to alteplase for stroke. Given differences between anterior circulation stroke (ACS) and posterior circulation stroke (PCS), we performed prespecified secondary analysis to investigate whether benefit of argatroban was different between ACS and PCS. METHODS: In secondary analysis of ARAIS, patients with definite stroke territories based on responsible vessel examination were classified into ACS and PCS. The primary outcome was a 90-day excellent functional outcome (modified Rankin Scale score of 0 to 1). The efficacy was compared between argatroban plus alteplase and alteplase alone. RESULTS: This study included 356 patients from the full analysis set of ARAIS trial: 283 in the ACS group and 73 in the PCS group. Compared with alteplase alone, a higher likelihood of 90-day excellent functional outcome was associated with argatroban plus alteplase in PCS group (78.1% versus 61.0%
adjusted RD, 14.4%
95% CI, 1.6% to 27.2%
p = 0.03), but similar in ACS group (61.7% versus 62.7%
adjusted RD, -2.4%
95% CI, -10.1% to 5.2%
p = 0.54). After controlling unbalanced sample size bias by propensity score matching, significant interaction between efficacy and stroke territories was found (p = 0.01). The risk of symptomatic intracranial hemorrhage was higher following argatroban plus alteplase than alteplase alone in ACS group (p = 0.02). INTERPRETATION: Argatroban plus alteplase, compared with alteplase alone, was associated with improved functional outcomes in PCS. This study first demonstrated better benefits of argatroban plus alteplase in PCS, which deserves to be confirmed.