Exploring the Efficacy and Safety of Argatroban as an Adjunct to Antiplatelet Therapy in Ischemic Stroke Patients: A Systematic Review and Meta-analysis.

Abstract

Acute ischemic stroke (AIS) is a major cause of disability and mortality worldwide. While antiplatelet therapy is standard for secondary prevention, many patients still experience early neurological deterioration (END). Argatroban, a direct thrombin inhibitor, can potentially limit thrombus progression and improve AIS's functional outcomes. This meta-analysis assessed the efficacy and safety of argatroban in combination with single (SAPT) or dual antiplatelet therapy (DAPT) compared to antiplatelets alone. Following PRISMA guidelines, a systematic search of PubMed, Scopus, and Web of Science was conducted until January 2025. Randomized controlled trials (RCTs) and cohort studies evaluating argatroban plus antiplatelets versus antiplatelets alone in AIS patients were included. The primary outcome was a 90-day modified Rankin Score (mRS) of 0-2. Secondary outcomes included mRS 0-1 and mRS 3-5 at 90 days, END, and National Institutes of Health Stroke Scale (NIHSS) improvement, stroke recurrence, intracranial hemorrhage (ICH), symptomatic intracranial hemorrhage (sICH), and mortality. We used the mean difference (MD) for continuous variables and odds ratio (OR) for dichotomous ones at 95% confidence intervals (CI) and a P-value of 0.05. A total of 14 studies (four RCTs and 10 cohort studies) were included. Compared to antiplatelets alone, argatroban significantly improved functional outcomes, increasing the incidence of mRS 0-2 (OR = 1.36 [95%CI: 1.05, 1.76, P = 0.02]) and mRS 0-1 (OR = 1.54 [95%CI: 1.08, 2.2, P = 0.02]) while reducing END (OR = 0.42 [95%CI: 0.21, 0.85, P = 0.02]). Argatroban was also associated with greater NIHSS score improvement (MD =  - 0.52 [95%CI: - 0.89, - 0.15, P = 0.005]). No significant differences were observed in mRS 3-5, stroke recurrence, ICH, sICH, or mortality. Subgroup analysis indicated that argatroban combined with DAPT showed the greatest benefits. Argatroban combined with antiplatelet therapy improves functional recovery and reduces END without increasing bleeding risks. These findings support its use, particularly with DAPT, in mild to moderate AIS management. Further large-scale RCTs are needed to optimize dosing strategies and patient selection.