Abstract TP049: Comparative Efficacy and Safety of Tenecteplase versus Reteplase in Acute Ischemic Stroke: An Indirect Meta-Analysis

Introduction: Intravenous thrombolysis with alteplase (tPA) has long been the standard for acute ischemic stroke (AIS), but its narrow therapeutic window, complex administration, and risk of symptomatic intracerebral hemorrhage have prompted exploration of alternative fibrinolytics. Tenecteplase (TNK) and reteplase are genetically engineered variants of alteplase with some notable differences. Both have been studied separately in AIS, but no direct head-to-head trials have been conducted. This study addresses this knowledge gap through an indirect comparison of randomized controlled trials, evaluating the relative efficacy and safety of TNK versus reteplase in AIS. Methods: We conducted a systematic review of RCTs evaluating intravenous thrombolysis with TNK or reteplase in AIS. The primary outcome was excellent functional recovery (mRS 0–1) at 90 days; secondary outcomes included good functional outcome (mRS 0–2), sICH, and 90-day mortality. Data on study design, demographics, interventions, and predefined outcomes were extracted. Indirect comparisons used the Bucher method. Analyses were performed in JASP, with p < 0.05 considered significant. Results: Thirteen RCTs were included—eleven comparing TNK with tPA and two comparing reteplase with tPA. Among indirect comparisons using tPA as the common comparator, TNK was linked to lower odds of achieving an excellent functional outcome compared to reteplase (odds ratio [OR], 0.74; 95% CI, 0.57–0.95). There was no significant difference between TNK and reteplase for good functional outcome (OR, 0.82; 95% CI, 0.60–1.12). The risk of symptomatic intracerebral hemorrhage did not differ significantly between the two agents (OR, 0.89; 95% CI, 0.42–1.87). Additionally, there was no significant difference in 90-day mortality between TNK and reteplase (OR, 0.84; 95% CI, 0.50–1.42). Conclusion: This indirect comparison indicates that TNK is associated with lower odds of achieving an excellent functional outcome at 90 days compared to reteplase. Since there are no direct head-to-head trials, these findings highlight a critical gap in evidence and emphasize the need for well-designed, sufficiently powered RCTs directly comparing TNK and reteplase in AIS. Such studies are vital to guide optimal thrombolytic choice, considering stroke severity and personalized treatment approaches.