Early Adjunctive Antiplatelets After Intravenous Thrombolysis in Acute Ischemic Stroke

Background: The role of early antiplatelet therapy following intravenous thrombolysis (IVT) for acute ischemic stroke (AIS) remains controversial because of concerns regarding hemorrhagic complications. Emerging randomized controlled trials (RCTs) have evaluated oral dual antiplatelet therapy (DAPT), intravenous glycoprotein IIb/IIIa inhibitors (GPI), and intravenous aspirin as adjunctive strategies after IVT, but their comparative efficacy and safety remain uncertain. Research Question: How do adjunctive oral DAPT, intravenous GPI, and intravenous aspirin compare with standard IVT alone in patients with AIS regarding functional outcomes, symptomatic intracranial hemorrhage (sICH), mortality, and major bleeding? Methods: We systematically searched PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov from inception through May 2026 for RCTs enrolling adults with AIS treated with IVT. Interventions were grouped into oral DAPT plus IVT, intravenous GPI plus IVT, and intravenous aspirin plus IVT, with IVT alone as the common comparator. Pairwise meta-analyses and a frequentist network meta-analysis were performed using the netmeta package in R. Primary efficacy outcomes were 90-day excellent functional outcome (modified Rankin Scale [mRS] 0-1) and functional independence (mRS 0-2). The primary safety outcome was sICH. Secondary outcomes included 90-day all-cause mortality and major bleeding. Treatment effects were pooled as odds ratios (ORs) with 95% confidence intervals (CIs), between-study heterogeneity was assessed using I 2 statistics, and interventions were ranked using P-scores. Results: Six RCTs comprising 4,665 patients were. None of the adjunctive antiplatelet strategies improved mRS 0-1 versus IVT alone: intravenous GPI (OR 1.30, 95% CI 0.90-1.87; p=0.158), oral DAPT (OR 1.19, 95% CI 0.77-1.82; p=0.429), or intravenous aspirin (OR 0.99, 95% CI 0.54-1.83; p=0.977). Similar findings were observed for mRS 0-2, with ORs of 1.20 (95% CI 0.82-1.76), 1.19 (95% CI 0.75-1.89), and 0.88 (95% CI 0.48-1.63), respectively. Intravenous GPI ranked highest for both efficacy outcomes (P-score 0.771 for mRS 0-1 and 0.716 for mRS 0-2), followed by oral DAPT. For safety, only intravenous aspirin was associated with a significant increase in sICH (OR 2.86, 95% CI 1.02-8.05; p=0.046), while oral DAPT and intravenous GPI were not. No significant differences were observed in 90-day all-cause mortality or major bleeding across treatment strategies. Conclusion: Among patients with AIS treated with IVT, adjunctive antiplatelet therapy did not improve 90-day functional outcomes. Intravenous GPI and oral DAPT ranked highest for efficacy, whereas intravenous aspirin increased sICH risk. Current evidence does not support routine use of adjunctive antiplatelet therapy after IVT, although oral DAPT may merit further study.