Introduction: Based on results of randomized controlled trials (RCTs) performed largely outside the US, tenecteplase (TNK) has increasingly replaced alteplase (tPA) for intravenous thrombolysis in acute ischemic stroke (AIS). Because practice patterns and patient populations outside the US can vary substantially from US-based cohorts, additional high-quality data on the safety of alteplase vs. tenecteplase within the US is needed. RCTs on this topic in the US have not been possible. Here, we present the results of a quasi-experimental method, regression discontinuity (RD), which can estimate causal effects and is of particular utility in settings where RCTs cannot be performed. Methods: From our prospectively collected multicenter registry, we identified patients who underwent IV thrombolysis for AIS between March 2022 and March 2024. All hospitals in the cohort transitioned from tPA to TNK on March 7, 2023, and patients were included if treated within 365 days before or after this date. The primary outcome was intracranial hemorrhage (ICH), with secondary outcomes of symptomatic ICH (sICH), functional independence (mRS 0-2) at 90 days and mortality. A sharp RD design was applied, using the exact time of the tPA-to-TNK switch as the cutoff, ensuring balance of measured and unmeasured confounders across tPA vs. TNK groups. Results: Among 908 patients who met inclusion criteria, the median age was 66 years (IQR:55-77), 48% were female, and median NIHSS was 7 (IQR: 4-14). 473 (52%) patients received tPA and 435 (48%) received TNK. Baseline presentation characteristics, including age, NIHSS, ASPECTS, and last know well to thrombolysis time, were not significantly different between groups at the switch cutoff date, supporting the RD assumption (Figure 1A-1D). In RD analysis, we observed no discontinuity in ICH at the TNK cutoff, indicating no statistically significant difference between tPA and TNK among patients near the cutoff (risk difference:-0.03; 95%-0.14,0.09) (Figure 1.E), nor in the secondary outcomes of sICH (risk difference:-0.10; 95%-0.21,0.0008), functional independence at 90 days (risk difference:0.27; 95%-0.19,0.73), or mortality (risk difference:-0.06; 95%-0.16,0.03). Conclusion: Our pseudo-randomized study design corroborated findings from RCT conducted outside the US, demonstrating equivalent safety and efficacy measures in tenecteplase and alteplase for treatment of acute ischemic stroke.
Farias et al. (Thu,) studied this question.
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