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Neurology
Published

Patterns and Clinical Implications of Hemorrhagic Transformation After Thrombolysis in Acute Ischemic Stroke: Results From the ENCHANTED Study

Authors

Yanan Wang, Toshiki Maeda, Shoujiang You, Chen Chen, Leibo Liu, Zien Zhou, Thompson G Robinson, Richard Iain Lindley, Candice Delcourt, Grant Mair, Joanna M Wardlaw, John Philip Chalmers, Hisatomi Arima, Yining Huang, Jong S Kim, Pablo M Lavados, Tsong-Hai Lee, Christopher Levi, Mark W Parsons, Sheila Co Martins, Jeyaraj Durai Pandian, Octavio M Pontes-Neto, Vijay K Sharma, Thang Huy Nguyen, Jiguang Wang, Simiao Wu, Ming Liu, Craig S Anderson, Xiaoying Chen, ENCHANTED Investigators

Abstract

Neurology. 2024 Dec 10;103(11):e210020. doi: 10.1212/WNL.0000000000210020. Epub 2024 Nov 14.

ABSTRACT

BACKGROUND AND OBJECTIVES: Hemorrhagic transformation may be a potentially devastating complication of IV thrombolysis (IVT) in acute ischemic stroke, but what degree of hemorrhage indicates the greatest negative effect is not known. We aimed to define the associations between hemorrhagic transformation patterns, classified according to clinical and imaging categories, and clinical outcomes after IVT.

METHODS: We conducted a post hoc analysis from the international Enhanced Control of Hypertension and Thrombolysis Stroke Study. Symptomatic intracerebral hemorrhage (sICH) was defined based on established criteria, such as the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) criteria. Asymptomatic intracerebral hemorrhage (aICH) was defined as any intracerebral hemorrhage that did not meet the criteria for sICH. Imaging subtypes of hemorrhagic transformation were assessed using the Heidelberg Bleeding Classification system. The primary outcome was death or major disability, defined by modified Rankin scale (mRS) scores 3-6 at 90 days. Secondary outcomes included death, death or disability (mRS 2-6), and poor health-related quality of life (HRQoL), defined as an overall heath utility score ≤0.7 (mean).

RESULTS: Of the 4,370 participants, 779 (17.8%) developed any intracranial hemorrhage (ICH), with a median time from randomization to hemorrhage of 23.5 hours (interquartile range 18.92-26.07). According to the SITS-MOST criteria, 62 patients (1.4% of 4,370) were classified as sICH, and 717 patients (16.4% of 4,370) were classified as aICH. sICH per SITS-MOST criteria was associated with death or major disability (odds ratio [OR] 23.05, 95% CI 8.97-59.23), death (OR 20.14, 95% CI 11.32-35.84), death or disability (OR 61.36, 95% CI 8.40-448.01), and poor HRQoL (OR 17.87, 95% CI 7.47-42.71). Similarly, aICH per SITS-MOST criteria was also associated with death or major disability (OR 2.23, 95% CI 1.84-2.70), death (OR 1.82, 95% CI 1.39-2.38), death or disability (OR 2.29, 95% CI 1.87-2.80), and poor HRQoL (OR 1.81, 95% CI 1.50-2.18). Comparable associations were observed for sICH and aICH defined by other criteria, as well as for imaging subtypes based on Heidelberg Bleeding Classification system.

DISCUSSION: All forms of post-IVT hemorrhagic transformation in acute ischemic stroke are associated with increased odds of poor clinical outcomes. Of note, aICH after IVT should not be considered clinically innocuous.

TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov (NCT01422616).

PMID:39541551 | DOI:10.1212/WNL.0000000000210020