Intracranial Hemorrhage in Patients With Stroke After Endovascular Treatment With or Without IV Alteplase

Importance: For patients with acute ischemic stroke due to anterior circulation large vessel occlusion and presenting directly to endovascular treatment (EVT)-capable centers, intravenous thrombolysis (IVT) before EVT raises concerns about intracranial hemorrhage (ICH), but details are not well understood. Objective: To determine the frequency and subtypes of ICH in patients treated with IVT plus EVT vs EVT alone and to determine the association between various ICH subtypes and patient functional outcomes. Data Sources: PubMed and MEDLINE were searched from database inception through March 9, 2023. Study Selection: Randomized clinical trials comparing EVT alone with IVT plus EVT for anterior circulation large vessel occlusion stroke were included. Data Extraction and Synthesis: Individual participant data were extracted following the Preferred Reporting Items for Systematic Review and Meta-Analyses of independent participant data (PRISMA-IPD) reporting guidelines. Data were pooled using a random-effects model. Data were analyzed between April 2024 and February 2025. Main Outcomes and Measures: The primary outcomes were ICH and its subtypes according to the Heidelberg Bleeding Classification (hemorrhagic infarction type 1 [HI1], hemorrhagic infarction type 2 [HI2], parenchymal hematoma type 1 [PH1], parenchymal hematoma type 2 [PH2], and others; symptomatic or asymptomatic ICH), which were evaluated using a mixed-model approach with multinomial or binary regression. Results: The analysis involved 2313 participants (1160 allocated to the IVT plus EVT group vs 1153 to EVT alone; median [IQR] age, 71 [62-78] years; 1025 female participants [44%]) from 6 studies. Any ICH occurred in 768 of 2261 participants (34%). IVT was associated with an increased rate of any ICH (411 of 1133 [36%] vs 357 of 1128 [32%]; adjusted odds ratio [OR], 1.23; 95% CI, 1.02-1.49; P = .03) and a higher rate of any parenchymal hematoma (PH1 or PH2) (82 of 1133 [7%] vs 61 of 1128 [5%]; adjusted OR, 1.54; 95% CI, 1.02-2.34; P = .04). Compared with participants without ICH, asymptomatic ICH (adjusted common OR, 0.55; 95% CI, 0.46-0.65) and symptomatic ICH (adjusted common OR, 0.08; 95% CI, 0.05-0.13) were both associated with worse functional outcomes, and there was a graded association of ICH radiologic patterns and patient outcomes. Conclusions and Relevance: In this individual participant data meta-analysis, compared with EVT alone, IVT plus EVT modestly increased the risk of ICH, notably any parenchymal hematoma. Although ICH was associated with worse functional outcomes, this effect may be offset by IVT's benefit in final successful reperfusion and early reperfusion.