Abstract 073: Thrombectomy Alone Versus Bridging Intravenous Alteplase in A US Population: Regression Discontinuity Analysis
Authors: Le Ngoc Mai , Kim Youngran , Salazar‐Marioni Sergio , Niktabe Arash , Ballekere Anjan , Abdelkhaleq Rania , Iyyangar Ananya , Azeem Hussain , Haussen Diogo , Grossberg Jonathan , Dolia Jaydevsinh , Pabaney Aqueel , Mohammaden Mahmoud , Majidi Shahram , Fifi Johanna T. , Nguyen Thanh , Abdalkader Mohamad , Klein Piers , Sugg Rebecca , Hassan Ameer , Tekle Wondwossen , Liebeskind David , Linfante Italo , Saei Hamzah , Valestin Gabrielle , Ortega‐Gutierrez Santiago , Siegler James , Mehta Brijesh , Linares Guillermo , Jumaa Mouhammad , Sessa Joy , Sheth Sunil , Nogueira Raul 
Published: March 2024

Introduction
Recent randomized controlled trials (RCT) failed to demonstrate the non‐inferiority of skipping IV tPA in patients with planned endovascular therapy (EVT). None of these studies included patients from the US due to regulatory challenges. Given that practice patterns vary relative to Asia, Australia, and Europe, we sought to address this topic using a validated alternative to RCTs, regression discontinuity (RD).

Methods
From the prospectively collected SVIN Registry encompassing all consecutive patients treated with EVT from 12 centers across the US, we identified patients from 12/2010 – 12/2021. RD design achieves quasi‐randomization and can determine causal effects by analyzing subjects on immediately adjacent sides of a cutoff. Here, we take advantage of the sharp drop in the likelihood of IV tPA treatment at the 4.5‐hour mark from the patients’ last known well time. Subjects immediately on either side of the cutoff have markedly different probabilities of receiving the treatment while sharing similar characteristics in other relevant aspects. Patients were excluded if they underwent EVT after inter‐hospital transfer, were inpatient at the time of acute ischemic stroke (AIS), received IV tPA outside the 4.5‐hour window, or were treated with EVT after the 10‐hour window, as these patients would not contribute to the RD analysis. The primary outcome was a good functional outcome defined as 90‐day mRS 0‐2 and was analyzed using validated RD analysis methods with local linear regressions and triangular kernel weights. Secondary endpoints included rates of symptomatic intracranial hemorrhage and substantial reperfusion.

Results
Among 961 patients who met inclusion criteria, all 12 EVT centers within the SVIN Registry were represented. The median age was 70 [IQR 58‐79], 48% were female, NIHSS was 17, and the most common occlusion location was M1 MCA (45%). There were no substantial differences in presentation characteristics between patients treated with IV tPA and without. We observed a significant fall (30%) in the probability of tPA around the cutoff time of 235 minutes from the last known well to hospital arrival (allowing 35 minutes for in‐hospital evaluation from the 4.5‐hour cutoff), while there were no significant differences in other relevant features including age, NIHSS, ASPECTS, and final reperfusion grade at the cutoff, validating the underlying RD assumptions (Figure A). In RD analysis, we observed no association between IV tPA treatment and functional independence at 90‐days in patients undergoing EVT (risk difference ‐0.29 (95% CI [‐2.75 to 2.15]) (Figure B), nor in the secondary outcomes of excellent outcomes (mRS 0‐1) at 90 days, mortality, symptomatic ICH or first pass reperfusion.

Conclusion
Here, we perform what we believe to be the strongest study to date examining the benefit of IV tPA in patients undergoing EVT for LVO AIS in a US‐based cohort, and we find no evidence of association with 90‐day functional independence, consistent with findings of RCTs performed outside the US.