Efficacy and Safety of Argatroban as an Adjunct to Antiplatelet Therapy in Ischemic Stroke: An Updated Systematic Review and Meta-analysis

Abstract

Acute ischemic stroke (AIS) is a life-threatening condition. Argatroban can limit thrombus progression and improve AIS’s functional outcomes. This study assessed the efficacy and safety of argatroban in combination with antiplatelet therapy compared to control. PubMed and Scopus were searched. Primary outcomes were Modified Rankin Scale (mRS) 0–2 and composite hemorrhage; secondary outcomes included mRS (0–1), early neurological deterioration (END), change in National Institutes of Health Stroke Scale (NIHSS) score, mortality, intracranial and organ hemorrhage. A random-effects model was used, with risk ratios (RRs) reported for binary outcomes, while mean differences (MDs) for continuous outcomes at 95% confidence intervals (CI) and a p-value of 0.05. 17 studies were included with a total of 51,703 and 18,759 patients in the argatroban and control group, respectively. The primary outcomes, mRS (0–2), and composite hemorrhage showed no significant difference between argatroban and control (RR: 1.03, CI: 0.97–1.10, p = 0.26 and RR: 1.10, CI: 0.98–1.23, p = 0.11, respectively). However, argatroban significantly reduced END (RR: 0.48, CI: 0.30–0.75, p < 0.05) and favored mRS (0–1) with RR:1.22 (CI: 1.01–1.48, p = 0.03). The change in NIHSS score and incidence of mortality, stroke recurrence, intracranial and organ hemorrhage was comparable between the two groups. Subgroup analyses by antiplatelet drug in the intervention and comparison groups confirmed that argatroban showed the most pronounced results when combined with DAPT. While the overall pooled analysis did not demonstrate increased hemorrhagic risk, subgroup analysis restricted to randomized controlled trials revealed a significant increase in composite and intracranial hemorrhage with argatroban. GRADE assessment of RCT-derived evidence indicated very low to high certainty across all outcomes. Argatroban as an adjunct to antiplatelet therapy did not significantly improve overall functional outcome (mRS 0–2) or reduce composite hemorrhage compared with antiplatelet therapy alone. However it appears safe and may reduce END significantly. Argatroban + antiplatelet therapy reduces END risk in AIS (RR: 0.48, CI: 0.30–0.75, p < 0.05). Argatroban + antiplatelet therapy improves change in NIHSS score change at discharge (MD 1.12, CI: 0.23–2.01, p = 0.01). Argatroban + antiplatelet therapy favors mRS (0–1) (RR:1.22, CI: 1.01–1.48, p = 0.03). No significant increase in the risk of composite hemorrhage with argatroban (RR: 1.10, CI: 0.98–1.23, p = 0.11). No difference in mRS 0–2 with argatroban (RR: 1.03, CI: 0.97–1.10, p = 0.26). Argatroban + antiplatelet therapy reduces END risk in AIS (RR: 0.48, CI: 0.30–0.75, p < 0.05). Argatroban + antiplatelet therapy improves change in NIHSS score change at discharge (MD 1.12, CI: 0.23–2.01, p = 0.01). Argatroban + antiplatelet therapy favors mRS (0–1) (RR:1.22, CI: 1.01–1.48, p = 0.03). No significant increase in the risk of composite hemorrhage with argatroban (RR: 1.10, CI: 0.98–1.23, p = 0.11). No difference in mRS 0–2 with argatroban (RR: 1.03, CI: 0.97–1.10, p = 0.26).