Xia Wang1, Keon-Joo Lee2, Tom J Moullaali1,3, Beom Joon Kim2, Qiang Li1, Hee-Joon Bae2, Cheryl Carcel1, Candice Delcourt1,4,5, Hisatomi Arima6, Shoichiro Sato7, Thompson G Robinson8, Lili Song9, Guofang Chen10, Jie Yang11, John Chalmers1, Craig S Anderson1,5,9, Richard Lindley1,12, Mark Woodward1,13. 1. The George Institute for Global Health, Faculty of Medicine, University of New South Wales, Sydney, Australia. 2. The Department of Neurology and Cerebrovascular Center, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Republic of Korea. 3. Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK. 4. Central Clinical School, University of Sydney, Sydney, Australia. 5. Department of Neurology, Royal Prince Alfred Hospital, Sydney, Australia. 6. Department of Public Health, Fukuoka University, Fukuoka, Japan. 7. Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Centre, Osaka, Japan. 8. Department of Cardiovascular Sciences, NIHR Leicester Biomedical Research Centre, University of Leicester, Leicester, UK. 9. The George Institute China, Peking University Health Science Center, Beijing, China. 10. Department of Neurology, Xuzhou Central Hospital Affiliated to Nanjing University of Chinese Medicine, Xuzhou, China. 11. Department of Neurology, the First Affiliated Hospital of Chengdu Medical College, Chengdu, China. 12. Westmead Hospital, University of Sydney, Sydney, Australia. 13. The George Institute for Global Health, University of Oxford, Oxford, UK.
Abstract
OBJECTIVES: Controversy persists over the benefits of low-dose versus standard-dose intravenous alteplase for the treatment of acute ischemic stroke. We sought to determine individual patient factors that contribute to the risk-benefit balance of low-dose alteplase treatment. METHODS: Observational study using data from the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED), an international, randomized, open-label, blinded-endpoint trial that assessed low-dose (0.6 mg/kg) versus standard-dose (0.9 mg/kg) intravenous alteplase in acute ischemic stroke patients. Logistic regression models were used to estimate the benefit of good functional outcome (scores 0 or 1 on the modified Rankin scale at 90 days) and risk (symptomatic intracerebral hemorrhage), under both regimens for individual patients. The net advantage for low-dose, relative to standard-dose, alteplase was calculated by dividing excess benefit by excess risk according to a combination of patient characteristics. The algorithms were externally validated in a nationwide acute stroke registry database in South Korea. RESULTS:Patients with an estimated net advantage from low-dose alteplase, compared with without, were younger (mean age of 66 vs. 75 years), had lower systolic blood pressure (148vs. 160 mm Hg), lower National Institute of Health Stroke Scale score (median of 8 vs. 16), and no atrial fibrillation (10.3% vs. 97.4%), diabetes mellitus (19.2% vs. 22.4%), or premorbid symptoms (defined by modified Rankin scale = 1) (16.3% vs. 37.8%). CONCLUSION: Use of low-dose alteplase may be preferable in acute ischemic stroke patients with a combination of favorable characteristics, including younger age, lower systolic blood pressure, mild neurological impairment, and no atrial fibrillation, diabetes mellitus, or premorbid symptoms.
RCT Entities:
OBJECTIVES: Controversy persists over the benefits of low-dose versus standard-dose intravenous alteplase for the treatment of acute ischemic stroke. We sought to determine individual patient factors that contribute to the risk-benefit balance of low-dose alteplase treatment. METHODS: Observational study using data from the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED), an international, randomized, open-label, blinded-endpoint trial that assessed low-dose (0.6 mg/kg) versus standard-dose (0.9 mg/kg) intravenous alteplase in acute ischemic strokepatients. Logistic regression models were used to estimate the benefit of good functional outcome (scores 0 or 1 on the modified Rankin scale at 90 days) and risk (symptomatic intracerebral hemorrhage), under both regimens for individual patients. The net advantage for low-dose, relative to standard-dose, alteplase was calculated by dividing excess benefit by excess risk according to a combination of patient characteristics. The algorithms were externally validated in a nationwide acute stroke registry database in South Korea. RESULTS:Patients with an estimated net advantage from low-dose alteplase, compared with without, were younger (mean age of 66 vs. 75 years), had lower systolic blood pressure (148 vs. 160 mm Hg), lower National Institute of Health Stroke Scale score (median of 8 vs. 16), and no atrial fibrillation (10.3% vs. 97.4%), diabetes mellitus (19.2% vs. 22.4%), or premorbid symptoms (defined by modified Rankin scale = 1) (16.3% vs. 37.8%). CONCLUSION: Use of low-dose alteplase may be preferable in acute ischemic strokepatients with a combination of favorable characteristics, including younger age, lower systolic blood pressure, mild neurological impairment, and no atrial fibrillation, diabetes mellitus, or premorbid symptoms.