Interaction of Intraprocedural Antiplatelets and Intravenous Thrombolysis in Acute Intracranial Stenting: RESISTANT Registry Subanalysis

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Abstract
Introduction/Objective: Acute intracranial stenting during endovascular thrombectomy (EVT) for ischemic stroke requires intraprocedural antiplatelet therapy (APT) to maintain patency. However, the hemorrhagic risk of combining APT with intravenous thrombolysis (IVT) remains uncertain. We evaluated the safety of IVT combined with conservative versus aggressive intraprocedural APT in patients requiring stenting during EVT. Methods: This multicenter RESISTANT registry subanalysis (2016–2023) included 823 adults. APT was categorized as conservative (aspirin +/− oral P2Y12) or aggressive (including GPIIb/IIIa inhibitors or cangrelor). The primary outcome was a composite of symptomatic intracranial hemorrhage (sICH) and parenchymal hematoma (PH1/PH2). Multivariable logistic regression assessed associations and interactions between IVT and APT. Results: A total of 823 patients were included: 44 (5.3%) received IVT + conservative APT, 130 (15.8%) No IVT + conservative APT, 145 (17.6%) IVT + aggressive APT, and 504 (61.2%) No IVT + aggressive APT. Frequencies of sICH‐PH1‐PH2 were 9.3% with IVT + conservative APT, 10.7% with IVT + aggressive APT, 3.2% with No IVT + conservative APT, and 9.9% with No IVT + aggressive APT. In multivariable analysis without interaction terms, neither IVT (aOR 1.18, 95% CI 0.58–2.27; p = 0.64) nor aggressive APT (aOR 2.10, 95% CI 0.92–5.69; p = 0.10) was independently associated with increased risk of sICH‐PH1‐PH2. However, in the interaction model, IVT within the conservative‐APT stratum (aOR 5.84, 95% CI 1.07–43.92; p = 0.05) and aggressive APT within the no‐IVT stratum (aOR 4.81, 95% CI 1.41–30.22; p = 0.03) were each associated with higher odds of sICH‐PH1‐PH2, while the IVT‐by‐APT interaction term was < 1 (aOR 0.15, 95% CI 0.02–0.94; p = 0.05), indicating attenuation of the joint effect on the multiplicative odds scale. Conclusion: Among patients requiring intracranial stenting during EVT, we found no evidence that IVT and aggressive intraprocedural APT act synergistically to increase hemorrhagic risk. Rather, the negative IVT‐by‐APT interaction suggested attenuation of the joint effect on the multiplicative odds scale, although patients receiving both therapies remained at increased hemorrhagic risk relative to the reference group.

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