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, ENCHANTED Investigators
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.
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 (Pinteraction=0.60), death (Pinteraction=0.56), or symptomatic intracerebral hemorrhage (Pinteraction=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.