Low versus standard dose intravenous alteplase in acute ischemic stroke
<h4>Background</h4> <p>Thrombolytic therapy for acute ischemic stroke with lower than standard dose of intravenous alteplase may improve recovery with reduced risk of intracerebral hemorrhage (ICH).</p> <h4>Methods</h4> <p>Using a 2-by-2 quasi-factorial open...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
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Massachusetts Medical Society
2016
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| _version_ | 1797089025267335168 |
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| author | Woodward, M Anderson, C Robinson, T Lindley, R Arima, H Lavados, P Lee, T Broderick, J Chen, X Chen, G Sharma, V Kim, J Thang, N Cao, Y Parsons, M Levi, C Huang, Y Olavarria, V Demchuk, A Bath, P Donnan, G Martins, S Pontes-Neto, O Silva, F Ricci, S Roffe, C Pandian, J Billot, L Li, Q Wang, X Wang, J Chalmers, J |
| author_facet | Woodward, M Anderson, C Robinson, T Lindley, R Arima, H Lavados, P Lee, T Broderick, J Chen, X Chen, G Sharma, V Kim, J Thang, N Cao, Y Parsons, M Levi, C Huang, Y Olavarria, V Demchuk, A Bath, P Donnan, G Martins, S Pontes-Neto, O Silva, F Ricci, S Roffe, C Pandian, J Billot, L Li, Q Wang, X Wang, J Chalmers, J |
| author_sort | Woodward, M |
| collection | OXFORD |
| description | <h4>Background</h4> <p>Thrombolytic therapy for acute ischemic stroke with lower than standard dose of intravenous alteplase may improve recovery with reduced risk of intracerebral hemorrhage (ICH).</p> <h4>Methods</h4> <p>Using a 2-by-2 quasi-factorial open label design, we randomly assigned 3310 patients eligible for thrombolytic therapy (median age 67 years, 63% Asian) within 4.5 hours of stroke onset, to test for noninferiority of low-dose (0.6mg/kg) compared with standard-dose (0.9mg/kg) intravenous alteplase. The trial included 940 patients co-randomized to intensive versus guideline-recommended blood pressure control. The primary outcome was death or disability at 90 days (scores 2 to 6 on the modified Rankin scale [mRS]; range 0, no symptoms, to 6, death). Secondary objectives included tests of superiority for centrally-adjudicated symptomatic ICH and noninferiority in ordinal analysis of the mRS (testing for improvement across scale categories). </p> <h4>Results</h4> <p>The primary outcome occurred in 855 of 1607 (53.2%) participants in low-dose and in 817 of 1599 (51.1%) in standard-dose group (odds ratio, 1.09; 95% confidence interval [CI], 0.95-1.25; exceeding noninferiority margin of 1.14, P=0.51 for noninferiority). Low-dose alteplase was non-inferior in the ordinal analysis of mRS (unadjusted common odds ratio 1.00; 95% CI, 0.89-1.13; P=0.04 for noninferiority). Major symptomatic ICH occurred in 1.0% and 2.1% in the low-dose and standard-dose groups (P=0.01); fatal ICH events occurred in 0.5% and 1.5% (P=0.01). Mortality at 90 days did not differ significantly (8.5% vs. 10.3%, P=0.07).</p> <h4>Conclusions</h4> <p>This trial of predominantly Asian patients with acute ischemic stroke did not demonstrate noninferiority of low-dose alteplase compared with standard-dose alteplase in death and disability at 90 days. There were significantly fewer symptomatic intracerebral hemorrhages with low-dose alteplase</p> |
| first_indexed | 2024-03-07T02:58:32Z |
| format | Journal article |
| id | oxford-uuid:b0266b00-cc06-4404-94fb-0d53b86911e8 |
| institution | University of Oxford |
| last_indexed | 2024-03-07T02:58:32Z |
| publishDate | 2016 |
| publisher | Massachusetts Medical Society |
| record_format | dspace |
| spelling | oxford-uuid:b0266b00-cc06-4404-94fb-0d53b86911e82022-03-27T03:54:26ZLow versus standard dose intravenous alteplase in acute ischemic strokeJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b0266b00-cc06-4404-94fb-0d53b86911e8Symplectic Elements at OxfordMassachusetts Medical Society2016Woodward, MAnderson, CRobinson, TLindley, RArima, HLavados, PLee, TBroderick, JChen, XChen, GSharma, VKim, JThang, NCao, YParsons, MLevi, CHuang, YOlavarria, VDemchuk, ABath, PDonnan, GMartins, SPontes-Neto, OSilva, FRicci, SRoffe, CPandian, JBillot, LLi, QWang, XWang, JChalmers, J<h4>Background</h4> <p>Thrombolytic therapy for acute ischemic stroke with lower than standard dose of intravenous alteplase may improve recovery with reduced risk of intracerebral hemorrhage (ICH).</p> <h4>Methods</h4> <p>Using a 2-by-2 quasi-factorial open label design, we randomly assigned 3310 patients eligible for thrombolytic therapy (median age 67 years, 63% Asian) within 4.5 hours of stroke onset, to test for noninferiority of low-dose (0.6mg/kg) compared with standard-dose (0.9mg/kg) intravenous alteplase. The trial included 940 patients co-randomized to intensive versus guideline-recommended blood pressure control. The primary outcome was death or disability at 90 days (scores 2 to 6 on the modified Rankin scale [mRS]; range 0, no symptoms, to 6, death). Secondary objectives included tests of superiority for centrally-adjudicated symptomatic ICH and noninferiority in ordinal analysis of the mRS (testing for improvement across scale categories). </p> <h4>Results</h4> <p>The primary outcome occurred in 855 of 1607 (53.2%) participants in low-dose and in 817 of 1599 (51.1%) in standard-dose group (odds ratio, 1.09; 95% confidence interval [CI], 0.95-1.25; exceeding noninferiority margin of 1.14, P=0.51 for noninferiority). Low-dose alteplase was non-inferior in the ordinal analysis of mRS (unadjusted common odds ratio 1.00; 95% CI, 0.89-1.13; P=0.04 for noninferiority). Major symptomatic ICH occurred in 1.0% and 2.1% in the low-dose and standard-dose groups (P=0.01); fatal ICH events occurred in 0.5% and 1.5% (P=0.01). Mortality at 90 days did not differ significantly (8.5% vs. 10.3%, P=0.07).</p> <h4>Conclusions</h4> <p>This trial of predominantly Asian patients with acute ischemic stroke did not demonstrate noninferiority of low-dose alteplase compared with standard-dose alteplase in death and disability at 90 days. There were significantly fewer symptomatic intracerebral hemorrhages with low-dose alteplase</p> |
| spellingShingle | Woodward, M Anderson, C Robinson, T Lindley, R Arima, H Lavados, P Lee, T Broderick, J Chen, X Chen, G Sharma, V Kim, J Thang, N Cao, Y Parsons, M Levi, C Huang, Y Olavarria, V Demchuk, A Bath, P Donnan, G Martins, S Pontes-Neto, O Silva, F Ricci, S Roffe, C Pandian, J Billot, L Li, Q Wang, X Wang, J Chalmers, J Low versus standard dose intravenous alteplase in acute ischemic stroke |
| title | Low versus standard dose intravenous alteplase in acute ischemic stroke |
| title_full | Low versus standard dose intravenous alteplase in acute ischemic stroke |
| title_fullStr | Low versus standard dose intravenous alteplase in acute ischemic stroke |
| title_full_unstemmed | Low versus standard dose intravenous alteplase in acute ischemic stroke |
| title_short | Low versus standard dose intravenous alteplase in acute ischemic stroke |
| title_sort | low versus standard dose intravenous alteplase in acute ischemic stroke |
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