Safety and efficacy of adjunctive tirofiban and eptifibatide in acute ischemic stroke: A systematic review and meta-analysis

INTRODUCTION AND OBJECTIVE: Acute ischemic stroke (AIS) is one of the most common cerebrovascular diseases, posing a substantial burden on public health systems and individuals. Tirofiban and eptifibatide are used alongside intravenous thrombolysis (IVT) in patients with AIS, as they are believed to improve clinical outcomes. We aimed to investigate the efficacy and safety of IV tirofiban or eptifibatide as adjunctive therapy versus using IVT alone in patients with AIS. METHODS: We conducted a systematic search using PubMed, Embase, and Clinicaltrials.gov to retrieve randomized controlled trials and observational studies comparing adjunctive tirofiban or eptifibatide to IVT alone in patients with AIS. The quality of included RCTs and observational studies was assessed using the revised Cochrane "Risk of Bias" tool (RoB 2.0) and Newcastle- Ottawa Scale (NOS), respectively. All statistical analyses were performed using RevMan 5.4, using the random effects model with Risk Ratio (RR) and Mean difference (MD) as effect measures. RESULTS: Our meta-analysis included eleven studies, including seven RCTs and four observational studies, involving 1,796 patients. Our results showed that the number of patients with functional independence in the adjunctive therapy group (mRS score 0-2 at 90 days) was comparable to IVT alone (11 studies; n = 1686; RR 1.10; 95% CI, 0.90 - 1.36). There was no evidence of publication bias. Sensitivity analysis with evidence from RCTs showed that adjunctive Tirofiban may improve functional independence at 90 days. The incidence of symptomatic intracranial hemorrhage (ICH) (8 studies; n = 1234; RR 0.74; 95% CI, 0.37 - 1.48) and mortality (11 studies; n = 1686; RR=1.18; 95% CI, 0.82-1.70) was also found to be comparable between the two groups. There was no significant difference between the two groups when assessing the risk of any ICH, asymptomatic ICH, major hemorrhage or systemic bleeding, and fatal ICH. The incidence of early neurologic deterioration and mean change in mRS score remained comparable between the two groups. CONCLUSION: Our meta-analysis suggests that while adjunctive tirofiban or eptifibatide with IVT do not yield benefits in terms of reducing mortality or improving functional independence at 90 days in AIS, emerging evidence from RCTs indicates that tirofiban may offer functional benefits, though this remains uncertain. Importantly, adjunctive therapy did not demonstrate a significant increase in bleeding risk in the analyzed studies. . These findings support the need for further large-scale, high-quality randomized controlled trials to explain the role of tirofiban in the management of AIS.