To assess the efficacy and safety of Argatroban as an adjunct therapy to the standard treatment for patients of acute ischemic stroke (AIS).

Argatroban, a direct thrombin inhibitor, has emerged as a novel treatment for AIS in recent trials and shows improved neurological outcomes. However, its use as an adjunct therapy has not been explored to much extent.

PubMed, Embase, and Cochrane Library databases were searched till September 2024. The primary efficacy outcomes evaluated were a modified Rankin Scale (mRS) of 0-1 after 90 days. Risk ratios (RR) and weighted (WMD) or standardized mean differences (SMD) were pooled for dichotomous and continuous outcomes using Review Manager 5.4.1 under the random effects model. Publication bias was assessed visually through the funnel plots and statistically through Egger’s regression.

Four RCTs with 1,578 patients were included in the analysis. Adjunctive argatroban did not significantly impact mRS of 0-1 (RR= 0.91, 95% CI [0.60, 1.37]; p = 0.64; I² = 64%), or mRS 0-2 (RR= 0.92, 95% CI [0.72, 1.17]; p = 0.49; I² = 56%) after 90 days. The control group had a significantly lower risk of at least one adverse outcome (RR= 1.25, 95% CI [1.02, 1.54]; p = 0.03; I² = 0%) as compared to argatroban adjunct therapy. No significant difference was observed between the two groups in NIHSS (WMD= 0.33, 95% CI [-0.42, 1.07]; p = 0.39; I² = 0%), ADL (SMD= 0.99, 95% CI [—0.88, 2.86]; p = 0.30; I² = 98%), sICH (RR= 1.26, 95% CI [0.56, 2.83]; p = 0.57; I² = 0%) and major systemic bleeding (RR= 0.92, 95% CI [0.21, 4.02]; p = 0.92; I² = 0%).

Adjunctive Argatroban therapy is not superior to standard therapy or placebo and has a higher incidence of at least one adverse outcome.