Beyond the Vessel: Investigating the Impact of Active Substance Use on Mechanical Thrombectomy Outcomes for Large Vessel Occlusion Strokestext_resourcesIntroduction Active substance use (ASU) is a major contributor to global morbidity, mortality, and cerebrovascular disease risk. However, limited data exist on the impact of ASU on outcomes following mechanical thrombectomy (MT) for large-vessel occlusion acute ischemic stroke (LVO-AIS). This study evaluated the relationship between ASU and both procedural and clinical outcomes after MT at a large urban comprehensive stroke center. Methods We retrospectively analyzed a prospectively maintained registry of anterior-circulation LVO-AIS patients who underwent MT between 2005 and 2024. Inclusion criteria were age ≥18 years, MT for LVO-AIS, and available historical or toxicology-confirmed substance use data. Patients were classified as having ASU involving alcohol, tobacco, cannabis (THC), cocaine, heroin, amphetamines, or opioids versus no active use or remote history. The primary outcome was 90-day modified Rankin Scale (mRS). Secondary outcomes included 24-hour NIHSS, symptomatic intracranial hemorrhage (sICH), successful reperfusion (mTICI 2b–3), length of stay (LOS), and procedural complications. Statistical comparisons utilized t-tests and chi-squared or Fisher’s exact tests. Results Among 3,855 screened cases, 3,662 met inclusion criteria. Substance-specific analyses revealed distinct trends. Alcohol use was associated with higher successful reperfusion rates (52.4% vs 30.3%, p < 0.0001) and modestly improved median 90-day mRS (3.0 [IQR 1–5] vs 3.0 [2–6], p < 0.0001). Tobacco use was likewise associated with better functional outcomes (mRS 3.0 [IQR 1–5] vs 3.0 [2–6], p = 0.0001) without significant differences in other metrics. THC use was also linked to improved functional outcomes (90-day mRS 2.0 [IQR 1–4] vs 3.0 [1–5], p = 0.002). In contrast, opioid use was associated with worse early and long-term neurologic outcomes (median 24-hour NIHSS 6.0 [2–17.8] vs 4.0 [1–11], p = 0.0021; 90-day mRS 4.0 [1.25–6.0] vs 3.0 [1–5], p = 0.0042). There were no significant differences in rates of sICH or procedural complications. Conclusions Active substance use was associated with variable post-thrombectomy outcomes. Alcohol, tobacco, and THC use correlated with improved reperfusion and recovery, whereas opioid use predicted poorer neurologic outcomes. These findings may reflect physiologic differences or comorbid factors among populations with ASU and highlight the need for further study in this understudied cohort.Karayi, GnaneswariAuthorGonzales, MirandaAuthorHong, DavidAuthorKim, RevynAuthorBi, LuluAuthorFeler, Joshua MDAuthorShaaya, Elias MDAuthorTorabi, Radmehr A. MDAuthorMoldovan, Krisztina MDAuthorJayaraman, Mahesh MDAuthorWolman, Dylan N. MDAuthorBrown University. Alpert Medical School. Scholarly Concentration Program. Translational Research in Medicineresearch programCerebrovascular diseaseSubstance Use DisorderNeurosurgeryEnglish2025Translational Research in MedicineAttribution 4.0 International (CC BY 4.0)In Copyright