Real-world experience with RESCUE BT2 tirofiban protocol versus standard care for select patients with acute ischemic stroke at a United States comprehensive stroke center: a single-center retrospective study

Background Tirofiban, a glycoprotein IIb/IIIa receptor inhibitor, has shown promise in acute ischemic stroke (AIS) without medium- or large-vessel occlusion. The RESCUE BT2 trial demonstrated improved functional outcomes with IV tirofiban versus aspirin, but was conducted predominantly in Han Chinese populations, limiting generalizability to U.S. practice. This study evaluated the safety, operational feasibility, and exploratory clinical associations of a RESCUE BT2-based tirofiban protocol at a U.S. comprehensive stroke center. Methods This retrospective single-center cohort study compared patients treated with tirofiban per RESCUE BT2 protocol (Nov 2023–June 2025) with a historical standard care cohort meeting similar eligibility criteria (Jan 2021–Oct 2023). Primary outcomes focused on safety, including any intracranial hemorrhage (ICH), symptomatic ICH, extracranial bleeding, thrombocytopenia, and mortality. Exploratory clinical outcomes included NIHSS trajectories, discharge modified Rankin Scale (mRS), discharge disposition, hospital length of stay, and available 90-day mRS. Multivariate regression models adjusted for baseline severity, early therapies, and neurological severity at the clinical decision point. Propensity score matching and/or multiple imputation were conducted as sensitivity analyses, and the results were interpreted as exploratory. Results Seventy-four patients were included (32 tirofiban, 42 standard care). No patients in the tirofiban group developed symptomatic or asymptomatic ICH, and no thrombocytopenia was observed. Extracranial bleeding occurred in 3 patients (9.4%). In adjusted exploratory analyses, tirofiban was associated with lower discharge NIHSS ( β = −2.199; 95% CI, −3.850 to −0.548; p = 0.011), greater NIHSS improvement from the decision point to discharge ( β = 2.815; 95% CI, 1.173–4.456; p = 0.001), and a favorable shift in discharge mRS (OR 0.274; 95% CI, 0.087–0.86; p = 0.027). In propensity-matched analysis, the direction of effect for discharge mRS was consistent but did not reach statistical significance. 90-day mRS analyses were limited by substantial differential missingness; complete-case and propensity-matched analyses were non-significant, and multiple-imputation results were sensitive to model assumptions. Conclusion Implementation of a RESCUE BT2-based IV tirofiban protocol in a U.S. comprehensive stroke center was feasible and demonstrated a favorable safety profile in carefully selected AIS patients. Exploratory associations with improved neurological trajectories warrant prospective evaluation in larger multicenter studies.