INTRODUCTION/PURPOSE Current American Heart Association and American Stroke Association guidelines recommend initiating aspirin as secondary prevention at least 24 hours after endovascular thrombectomy (EVT) in patients with acute ischemic stroke. However, emerging evidence suggests that targeted periprocedural antiplatelet strategies may improve functional outcomes without substantially increasing the rate of symptomatic intracranial hemorrhage (sICH). This review evaluates the role of tirofiban and other antiplatelet agents compared with aspirin alone and discusses how decision‐based guideline updates could impact patient outcomes. MATERIALS/Methods A PubMed search was conducted for English‐language meta‐analyses, randomized controlled trials (RCTs), and cohort studies from 1995 to 2025 evaluating functional and safety outcomes of peri‐ or post‐procedural antiplatelet therapy in EVT patients. Case reports and small series (<10 patients) were excluded. RESULTS Periprocedural therapy: In our analysis, we evaluated tirofiban, argatroban, eptifibatide, and cangrelor. The strongest evidence supports tirofiban, which improves recanalization rates and long‐term functional outcomes without increasing sICH or mortality. In the latest meta‐analysis, which included cohort studies and one RCT, EVT patients receiving tirofiban had improved 90‐day modified Rankin Scale (mRS 0‐2), with an odds ratio of 1.24 (Sun et al., 2021), without a significant difference in sICH risk. Additional retrospective analyses further support an association of tirofiban with improved outcomes without added hemorrhagic risk (Guan et al., 2023; Sun et al., 2024; Wang et al., 2023). More recent trials confirm higher recanalization rates with intravenous tirofiban (Lin et al., 2025) but have not shown a significant difference in functional outcomes (RESCUE BT Trial Investigators, 2022). In contrast, intravenous aspirin during EVT was associated with increased sICH without functional benefit (van der Steen et al., 2022). Extrapolating these findings to U.S. EVT volumes suggests that approximately 3,000 additional patients annually could regain independence if tirofiban were adopted as a standard periprocedural agent. More targeted modeling based on selective use in high‐benefit subgroups—such as patients with residual large‐vessel stenosis, stent placement, or incomplete reperfusion—suggests 250‐600 patients each year could benefit from a tailored implementation approach. Post‐procedural therapy: Limited studies suggest that early initiation of dual antiplatelet therapy (DAPT) after EVT appears safe and may improve long‐term functional outcomes, though evidence remains insufficient to support universal adoption. Clinical Implications and Guideline Adaptation: These findings support a decision‐based update to current guidelines: • Standard approach: Continue aspirin monotherapy for most EVT patients. • Selective tirofiban use: Consider periprocedural tirofiban in patients with incomplete reperfusion, tandem occlusions, intracranial stent placement, or high thrombus burden. • Early DAPT: Consider short‐term dual antiplatelet therapy in selected high‐risk cases, pending further RCT evidence. CONCLUSION Tirofiban demonstrates the strongest evidence among evaluated agents for improving functional outcomes after EVT compared with standard treatment with aspirin alone, without significantly increasing hemorrhagic risk. We propose selective integration of tirofiban into periprocedural practice, particularly for patients with tandem occlusions, stent placement, or incomplete reperfusion. Adopting this decision‐based approach could meaningfully improve recovery for hundreds of U.S. stroke patients each year. Further RCTs are warranted to refine patient selection and confirm the benefits of updated guideline strategies.
Veltre et al. (Sat,) studied this question.