Body Weight in Relation to the Effectiveness of Intravenous Alteplase in Acute Ischemic Stroke: The ENCHANTED Trial

BACKGROUND: The prognostic significance of body weight in patients receiving thrombolysis for acute ischemic stroke remains uncertain. This study aimed to determine whether body weight modifies the comparative effects of low- versus standard-dose intravenous alteplase and to evaluate the associations of body weight and clinical outcomes in patients with acute ischemic stroke. METHODS: A post hoc analysis of the ENCHANTED trial (Enhanced Control of Hypertension and Thrombolysis Stroke Study), an international partial-factorial randomized controlled trial comparing low-dose (0.6 mg/kg) versus standard-dose (0.9 mg/kg) intravenous alteplase and intensive (target systolic blood pressure 130–140 mm Hg) versus guideline-recommended (target systolic blood pressure <180 mm Hg) treatment. The primary outcome was poor functional outcome at 90 days, defined as a modified Rankin Scale score of 2 to 6 (versus 0–1). For the first objective, the exposure was defined as alteplase dose and body weight, whereas for the second objective, body weight alone was considered as the exposure. Logistic regression models were performed to analyze the association between body weight and outcome. The association shape between treatment effect and body weight was evaluated using restricted cubic splines. RESULTS: Among 3206 patients (mean age, 66.6 years; female 37.9%) in the alteplase-dose arm, body weight did not significantly modify the comparative effects of low- versus standard-dose alteplase on functional recovery ( P interaction =0.60), death ( P interaction =0.56), or symptomatic intracerebral hemorrhage ( P interaction =0.46). In the full cohort of 4458 patients (mean age 66.7 years; female 37.8%), a nonlinear relationship was observed between continuous body weight and 90-day modified Rankin Scale score, with an inflection point at ≈74 kg. Patients weighing <74 kg had a significantly higher likelihood of poor functional outcome (odds ratio, 1.41 [95% CI, 1.06–1.87]; P =0.017) and death (1.65 [95% CI, 1.04–2.61]; 0.03), but not an increase in symptomatic intracerebral hemorrhage. CONCLUSIONS: There was no evidence of effect modification by body weight on the effectiveness of low- versus standard-dose intravenous alteplase in patients with acute ischemic stroke. Low body weight predicts a poor outcome but not an increased risk of symptomatic intracerebral hemorrhage after thrombolysis treatment for acute ischemic stroke. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01422616. URL: https://anzctr.org.au ; Unique identifier: ACTRN12611000236998.

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Journal
Stroke
Published
2026-09-28
DOI
https://doi.org/10.1161/strokeaha.125.053569
Primary Topic
Acute Ischemic Stroke Management
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article

Body Weight in Relation to the Effectiveness of Intravenous Alteplase in Acute Ischemic Stroke: The ENCHANTED Trial

Andrew M. Demchuk, Pablo M. Lavados, Geoffrey Alan Donnan, Candice Delcourt et al.
Stroke
Acute Ischemic Stroke Management
article

Body Weight in Relation to the Effectiveness of Intravenous Alteplase in Acute Ischemic Stroke: The ENCHANTED Trial

Andrew M. Demchuk, Pablo M. Lavados, Geoffrey Alan Donnan, Candice Delcourt, Thompson Gordon Robinson, OCTÁVIO MARQUES PONTES-NETO, Lili Song, Richard I. Lindley, Jeyaraj Durai Pandian, Philip M. Bath, Joseph P. Broderick, Mark William Parsons, Hisatomi Arima, Guofang Chen, Tsong-Hai Lee, Yilun Ge, On Behalf Of The ENCHANTED Investigators, Craig S. Anderson, John Chalmers, Xiaoying Chen, Xia Wang, Sheila O. Martins, Joseph P Broderick, Octavio M Pontes-Neto, Xia Wang, Jeyaraj D Pandian, Guofang Chen, Geoffrey A Donnan, Xiaoying Chen, Chunfeng Liu, Andrew M Demchuk, Thang H Nguyen, Richard I Lindley, Sheila O Martins, Mark W Parsons, Pablo M Lavados, Candice Delcourt, Tsong-Hai Lee, John Chalmers, Thompson G Robinson, Craig S Anderson, Lili Song, Yijie Gao
article en

Abstract

BACKGROUND: The prognostic significance of body weight in patients receiving thrombolysis for acute ischemic stroke remains uncertain. This study aimed to determine whether body weight modifies the comparative effects of low- versus standard-dose intravenous alteplase and to evaluate the associations of body weight and clinical outcomes in patients with acute ischemic stroke. METHODS: A post hoc analysis of the ENCHANTED trial (Enhanced Control of Hypertension and Thrombolysis Stroke Study), an international partial-factorial randomized controlled trial comparing low-dose (0.6 mg/kg) versus standard-dose (0.9 mg/kg) intravenous alteplase and intensive (target systolic blood pressure 130–140 mm Hg) versus guideline-recommended (target systolic blood pressure <180 mm Hg) treatment. The primary outcome was poor functional outcome at 90 days, defined as a modified Rankin Scale score of 2 to 6 (versus 0–1). For the first objective, the exposure was defined as alteplase dose and body weight, whereas for the second objective, body weight alone was considered as the exposure. Logistic regression models were performed to analyze the association between body weight and outcome. The association shape between treatment effect and body weight was evaluated using restricted cubic splines. RESULTS: Among 3206 patients (mean age, 66.6 years; female 37.9%) in the alteplase-dose arm, body weight did not significantly modify the comparative effects of low- versus standard-dose alteplase on functional recovery ( P interaction =0.60), death ( P interaction =0.56), or symptomatic intracerebral hemorrhage ( P interaction =0.46). In the full cohort of 4458 patients (mean age 66.7 years; female 37.8%), a nonlinear relationship was observed between continuous body weight and 90-day modified Rankin Scale score, with an inflection point at ≈74 kg. Patients weighing <74 kg had a significantly higher likelihood of poor functional outcome (odds ratio, 1.41 [95% CI, 1.06–1.87]; P =0.017) and death (1.65 [95% CI, 1.04–2.61]; 0.03), but not an increase in symptomatic intracerebral hemorrhage. CONCLUSIONS: There was no evidence of effect modification by body weight on the effectiveness of low- versus standard-dose intravenous alteplase in patients with acute ischemic stroke. Low body weight predicts a poor outcome but not an increased risk of symptomatic intracerebral hemorrhage after thrombolysis treatment for acute ischemic stroke. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01422616. URL: https://anzctr.org.au ; Unique identifier: ACTRN12611000236998.

StrokeVol. 57(10)
The University of Sydney (AU), The Royal Melbourne Hospital (AU), Universidad del Desarrollo (CL), University of Nottingham (GB), University of Leicester (GB), The University of Melbourne (AU), University of Calgary (CA), Christian Medical College, Vellore (IN), Chang Gung University (TW), Universidade de São Paulo (BR), University of Toronto (CA), Fudan University (CN), Royal Prince Alfred Hospital (AU), Liverpool Hospital (AU), Clínica Alemana (CL), UNSW Sydney (AU), Fukuoka University (JP), National Institute for Health and Care Excellence (GB), National Institute for Health and Care Research (GB), Soochow University (CN), Hospital de Clínicas de Porto Alegre (BR), Institute of Mental Health (GB), Christian Medical College (IN), The George Institute for Global Health (AU), Linkou Chang Gung Memorial Hospital (TW), Second Affiliated Hospital of Soochow University (CN), NIHR Leicester Cardiovascular Biomedical Research Unit (GB), Xuzhou Central Hospital (CN), Westmead Institute (AU), Ingham Institute (AU), Children's Hospital 1 (VN), South Western Sydney Local Health District (AU), Shanghai Center for Brain Science and Brain-Inspired Technology (CN), NIHR Leicester Biomedical Research Centre (GB), Hotchkiss Brain Institute (CA), University of Cincinnati (US), University of Cincinnati Medical Center (US), Macquarie University (AU)
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Acute Ischemic Stroke Management
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