Jay Shah, MD

Wada T, Yasunaga H, Horiguchi H, Matsubara T, Fushimi K, Nakajima S, and Naoki Yahagi N. Outcomes of Argatroban Treatment in Patients With Atherothrombotic Stroke: Observational Nationwide Study in Japan. Stroke. 2016   

Three randomized trials have suggested that argatroban is effective and safe for early therapy in acute ischemic stroke. However, these trials were small and a meta-analysis concluded early anticoagulants were not beneficial.

There has been some suggestion that argatroban may play a role in neuroprotection possibly due to its thrombin inhibition effects. This retrospective observational study investigated argatroban safety and efficacy in patients with acute ischemic strokes using a Japanese database that includes various parameters such as demographics, diagnosis, drugs used, and outcomes. In Japan, argatroban is recommended in patients with atherothromotic stroke within 48 hours from symptom onset. Argatroban is infused continuously at dose of 60mg daily for first 48 hours followed by twice daily 10mg infusions for the next 5 days. Inclusion criteria included atherothromotic stroke, admission within 1 day of stroke and antiplatelet agents during hospitalization. Patients who received thrombolysis or underwent endovascular intervention were excluded. Patients were then divided into 2 groups: those who received argatroban on admission and those who did not. Outcomes were 7-day mortality, hemorrhagic complications and modified rankin score (mRS) on discharge. In total, 2289 pairs of patients were included. In this population, there were no significant differences in the primary outcomes. Therefore, there was no added benefit of argatroban on outcomes.  

A strength of this study is the use of propensity score matching in order to compensate for lack of blinding. However, bias is still possible in that important parameters may not have been captured within demographics and other clinical parameters. Rationale for clinical decision making (i.e. whether to treat with argatroban) is not directly available but inferred from other parameters. Other limitations include the exclusion of patients receiving thrombolytics, which could potentially increase hemorrhage risk and omission of National Institutes of Health Stroke Scale which serves as a barometer of stroke severity. Lastly, given the retrospective nature of the study, the nature of the atherosclerotic disease could not be graded. It may be of interest if outcome differences exist between mild to moderate carotid stenosis (<70%) versus severe stenosis (>70%).