Efficacy and safety of argatroban in the management of acute ischemic stroke: A systematic literature review and meta-analysis.

ABSTRACT

BACKGROUND: Acute ischemic stroke (AIS) is a leading cause of death and disability. AIS is caused by an embolus or thrombus that restricts blood flow to the brain tissue. Despite intravenous thrombolysis and endovascular thrombectomy, a substantial number of patients do not achieve effective reperfusion. Argatroban, a direct thrombin inhibitor, can potentially improve neurological outcomes in AIS patients. However, there are conflicting results in the medical literature regarding the efficacy and safety of argatroban in this context. OBJECTIVE: This study aims to evaluate the efficacy and safety of argatroban as monotherapy or adjunct therapy for acute ischemic stroke. METHODS: Five major databases (PubMed, Embase, Scopus, Web of Science, and Cochrane Library) were searched for randomized controlled trials (RCTs) that compared the efficacy and safety of using argatroban alone or in combination with recombinant tissue plasminogen activator (r-TPA) in the management protocol of the AIS. We used Review Manager Software (RevMan 5.4.1) for data analysis. RESULTS: We included 1393 patients from eight RCTs (of them, 726 were treated with argatroban alone or combined with r-TPA, while 667 received the placebo, standard therapy (standard treatments based on current guidelines including antihypertensive, antiplatelet agents, and statins) or endovascular r-TPA). Neither argatroban vs control nor argatroban with r-TPA vs r-TPA showed significant difference regarding the activity in daily living; (SMD= 1.69, 95% CI [-0.23, 3.61]; p = 0.09), (SMD= 0.99, 95% CI [-0.88, 2.86]; p = 0.30), respectively. Also, there was no significant difference in the National Institutes of Health Stroke Scale (NIHSS) score at seven days, the number of patients achieving modified Rankin Scale (mRS) of 0-1 or 0-2 at 90 days (p > 0.05). Argatroban did not significantly increase the risk of adverse events or symptomatic intracranial hemorrhage (ICH), or major systemic bleeding compared to control or r-TPA (p > 0.05) CONCLUSIONS: Argatroban does not demonstrate superior efficacy compared to placebo or standard therapy in terms of ADL, NIHSS and mRS outcomes. Importantly, argatroban does not significantly increase the incidence of adverse events, including symptomatic ICH and systemic bleeding.