Safety and preliminary efficacy of argatroban plus dual antiplatelet therapy for acute mild to moderate ischemic stroke with large artery atherosclerosis

Objective Previous studies suggest the benefit of dual antiplatelet therapy (DAPT) for acute ischemic stroke with large artery atherosclerosis (LAA) etiology, but there is no study about the effect of DAPT plus anticoagulant in this population. Methods A prospective single arm trial was performed to determine the effect of DAPT combined with argatroban on acute mild to moderate ischemic stroke patients with LAA, which was compared with historical populations. The main outcome was the proportion of early neurological deterioration (END). The secondary outcomes included scores of 0 to 1 and 0 to 2 on the modified Rankin Scale (mRS) at 90 days, and changes in National Institutes of Health Stroke Scale (NIHSS) from baseline to day 7 after admission. The safety outcomes included intracranial hemorrhage at 7 days, organ hemorrhage, and all-cause mortality at 90 days. Results A total of 120 patients with argatroban plus DAPT were prospectively enrolled and 529 patients with only DAPT were retrospectively collected. There was no significant difference in baseline characteristics between groups. Compared with control group, combined treatment group had lower proportion of END (4.2% vs. 10.0%, adjusted p = .046), more reduction in NIHSS score from the baseline to day 7 after admission (1.06 +/- 2.03 vs. 0.39 +/- 1.97, adjusted p = .003), and higher proportion of mRS (0-2) at 90 days (87.5% vs. 79.2%, adjusted p = .048). No intracranial hemorrhage was found between groups. Conclusions This is the first report that short-term argatroban combined with DAPT seems to be safe and may effectively prevent END and improve neurological prognosis for acute mild to moderate ischemic stroke patients with LAA; however, interpretation of the conclusion required caution due to nonrandomized controlled trial with medium sample size.