Argatroban Treatment in Acute Ischemic Stroke: Multicenter, Randomized, Aspirin-Controlled Study

ABSTRACT

BACKGROUND: Argatroban, a direct thrombin inhibitor, has been suggested to be beneficial in acute ischemic stroke by preventing microthrombi formation. The aim of this multicenter, aspirin-controlled, randomized trial is to determine the safety and the efficacy of argatroban compared with aspirin in acute ischemic stroke. METHODS: The patients within 48 hours of noncardioembolic ischemic stroke were recruited from 8 centers. Argatroban was infused continuously at 2.5 mg/hr for the first 48 h, and then 10mg of argatroban was infused over 3 h twice a day on days 3-7. Control group received aspirin 300 mg/day for 7 days. The primary outcome was the NIHSS at 30 days and the secondary outcome was Barthel index (BI) and modified Rankin scale (mRS) at 90 days. The safety was evaluated by the incidence of bleeding complication. RESULTS: A total of 236 patients (123 for argatroban and 113 for aspirin) were included. NIHSS at 30 days, BI at 90 days and mRS at 90 days did not show significant difference between the argatroban and the aspirin group (3.1 +/- 3.1 vs 3.5 +/- 3.0, 88.9 +/- 22.5 vs 86.2 +/- 23.8, 1.4 +/- 1.1 vs 1.6 +/- 1.3, p>0.3, respectively). Post hoc analysis revealed that as for the patients who were treated within 24 hours after onset, numbers of patients with NIHSS=1 at 30 days were larger in the argatroban group (23 of 49) than in the aspirin group (10 of 40) (p=0.03). Bleeding complication was not different between the two groups (2 of 123 vs 0 of 113 p>0.4). CONCLUSIONS: Argatroban treatment is relatively safe in acute ischemic stroke. The efficacy of argatroban is not superior to aspirin. However, argatroban may be more beneficial in some subgroup of stroke patients than aspirin.