Reciprocal Relationship Between Early Reperfusion and First-pass Effect in Tenecteplase versus Alteplase before Stroke Thrombectomy
Kelsey Kline1, Tyler Bielinski1, Grant Badger1, Veronica Bohl1, Sina Hemmer2, Wysteria Stedman3, Oded Goren4, Jiang Li5, Clemens Schirmer2, Philipp Hendrix3
1Geisinger Commonwealth School of Medicine, Geisinger College of Health Sciences, 2Department of Neurosurgery, Geisinger Wyoming Valley, 3Geisinger Medical Center, 4Department of Neurosurgery, Geisinger Medical Center, 5Weis Center for Research, Geisinger
Objective:
To investigate the interplay of early reperfusion (ER) and first-pass effect (FPE) between patients receiving thrombolysis with tenecteplase (TNK) and alteplase (TPA) prior to endovascular treatment (EVT).
Background:
In large vessel occlusion stroke (LVOS) thrombectomy, ER and FPE are key procedural endpoints. TNK’s greater fibrin specificity may allow for higher ER than TPA, but the impact on FPE is unclear. We hypothesized that higher ER with TNK may preferentially eliminate thrombi that are easily retrievable on the first pass, leaving behind a greater proportion of EVT-resistant clots and thereby reducing FPE. Conversely, because TPA achieves less early lysis, more of these easily retrievable clots remain available for mechanical extraction, resulting in higher FPE despite lower ER.
Design/Methods:
Patients from two U.S. stroke centers with consecutive anterior circulation LVOS treated with intravenous thrombolysis prior to EVT were reviewed. ER was defined as eTICI 2b-3 on initial angiography. FPE was defined as eTICI 2c-3 after a single pass without rescue maneuvers. Predictors of ER and FPE were identified using multivariable logistic regression. Ordinal logistic regression assessed associations of thrombolytic agent, ER, and FPE with 90-day modified Rankin Scale (mRS) shift.
Results:
Among 299 patients (TNK 201, TPA 98), 60 (20.1%) experienced ER with increased rates in TNK (24.4%) than TPA (11.2%, aOR 2.54, 95% CI 1.19-5.42). Of the 239 that proceeded to EVT, FPE was less frequent with TNK (30.3%) than TPA (40.2%, aOR 0.50. 95% CI 0.27-0.91). ER and FPE each independently predicted better functional outcome, but functional outcomes were similar between TNK and TPA overall.
Conclusions:
The benefit of higher ER rates with TNK may be offset by greater FPE with TPA, resulting in comparable outcomes. This ER-FPE trade-off supports a selective depletion hypothesis, which, if confirmed in prospective studies, may have important implications for endpoint selection and interpretation in future bridging thrombolysis trials.
Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff.