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Publications

Journal Article Ahead of print

PubMed: 42644244 DOI: 10.1161/STROKEAHA.125.053569

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

Stroke

Authors: Yilun Ge, Yijie Gao, Xiaoying Chen, Chunfeng Liu, Richard I Lindley, Hisatomi Arima, Guofang Chen, Candice Delcourt, Philip M Bath, Joseph P Broderick, Andrew M Demchuk, Geoffrey A Donnan, Pablo M Lavados, Tsong-Hai Lee, Sheila O Martins, Jeyaraj D Pandian, Mark W Parsons, Octavio M Pontes-Neto, Thang H Nguyen, John Chalmers, Lili Song, Thompson G Robinson, Xia Wang, Craig S Anderson

Affiliations

  • The George Institute for Global Health, Faculty of Medicine (Y. Ge, Y. Gao, X.C. H.A. C.D. J.C. L.S. X.W. C.S.A.), University of New South Wales, Sydney, Australia.
  • University of Toronto, Ontario, Canada (Y. Ge).
  • Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of SooChow University, Suzhou, China (C.L.).
  • Westmead Applied Research Centre, Faculty of Medicine and Health, The University of Sydney, New South Wales, Australia (R.I.L.).
  • Department of Preventive Medicine and Public Health, Faculty of Medicine, Fukuoka University, Japan (H.A.).
  • Department of Neurology, Xuzhou Central Hospital, China (G.C.).
  • Department of Clinical Medicine, Faculty of Medicine, Health and Human Sciences, Macquarie University, New South Wales, Australia (C.D.).
  • Stroke Trials Unit, Mental Health & Clinical Neuroscience, University of Nottingham, United Kingdom (P.M.B.).
  • Department of Neurology and Rehabilitation Medicine, University of Cincinnati Neuroscience Institute, University of Cincinnati, OH (J.P.B.).
  • Departments of Clinical Neurosciences and Radiology, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Canada (A.M.D.).
  • Melbourne Brain Centre, Royal Melbourne Hospital, University of Melbourne, Victoria, Australia (G.A.D.).
  • Department of Neurology and Psychiatry, Clinica Alemana de Santiago, Clinica Alemana Universidad del Desarrollo School of Medicine, Chile (P.M.L.).
  • Stroke Center and Department of Neurology, Linkou Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taoyuan, Taiwan (T.-H.L.).
  • Stroke Division of Neurology Service, Hospital de Clínicas de Porto Alegre, University of Rio Grande do Sul, Brazil (S.O.M.).
  • Department of Neurology, Christian Medical College, Ludhiana, India (J.D.P.).
  • Department of Neurology, Liverpool Hospital (M.W.P.), University of New South Wales, Sydney, Australia.
  • South Western Sydney Clinical School, New South Wales, Australia (M.W.P.).
  • The Ingham Institute for Applied Medical Research, Sydney, New South Wales, Australia (M.W.P.).
  • Department of Neurosciences and Behavioral Sciences, University of Sao Paulo, Ribeirao Preto Medical School, Brazil (O.M.P.-N.).
  • Department of Cerebrovascular Disease, The People 115 Hospital, Ho Chi Min, Vietnam (T.H.N.).
  • Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China (L.S. C.S.A.).
  • Department of Cardiovascular Sciences, University of Leicester, United Kingdom (T.G.R.).
  • National Institute for Health and Care Research Leicester Biomedical Research Centre, United Kingdom (T.G.R.).
  • Neurology Department, Royal Prince Alfred Hospital, Sydney, Australia (C.S.A.).

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.

MeSH

Cerebral Hemorrhage, Hemorrhage, Blood, Ischemic Stroke, Stroke, Tissue Plasminogen Activator, Blood Pressure, Cerebrovascular Circulation, Cerebrovascular Disorders, Body Weight, Therapeutics, Prognosis