Low-dose versus standard-dose intravenous alteplase in acute ischemic stroke

New England Journal of Medicine

Volumn 374, Issue 24, 2016, Pages 2313-2323

  Anderson, C S ^a,b,e   Robinson, T ^j   Lindley, R I ^a,b   Arima, H ^a,b,n   Lavados, P M ^o,p   Lee, T H ^q   Broderick, J P ^r   Chen, X ^a,b   Chen, G ^g   Sharma, V K ^s   Kim, J S ^t   Thang, N H ^u   Cao, Y ^h   Parsons, M W ^c   Levi, C ^c   Huang, Y ^f   Olavarria V V ^o   Demchuk, A M ^v   Bath, P M ^k   Donnan, G A ^d   Martins, S ^w   Pontes Neto, O M ^x   Silva, F ^y   Ricci, S ^z   Roffe, C ^l   Pandian, J ^aa   Billot, L ^a,b   Woodward, M ^a,b,m,ab   Li, Q ^a,b   Wang, X ^a   Wang, J ⁱ   Chalmers, J ^a,b   more..

^a ROYAL PRINCE ALFRED HOSPITAL   (Australia)

^b UNIVERSITY OF SYDNEY   (Australia)

^c UNIVERSITY OF NEWCASTLE   (Australia)

^d FLOREY INSTITUTE OF NEUROSCIENCE AND MENTAL HEALTH   (Australia)

^e PEKING UNIVERSITY   (China)

^f PEKING UNIVERSITY FIRST HOSPITAL   (China)

^g XUZHOU CENTRAL HOSPITAL   (China)

^h SOOCHOW UNIVERSITY   (China)

ⁱ SHANGHAI JIAO TONG UNIVERSITY SCHOOL OF MEDICINE   (China)

^j UNIVERSITY OF LEICESTER   (United Kingdom)

^k UNIVERSITY OF NOTTINGHAM   (United Kingdom)

^l UNIVERSITY HOSPITAL OF NORTH STAFFORDSHIRE   (United Kingdom)

^m UNIVERSITY OF OXFORD   (United Kingdom)

ⁿ FUKUOKA UNIVERSITY   (Japan)

^o UNIVERSIDAD DEL DESARROLLO   (Chile)

^p UNIVERSITY OF CHILE   (Chile)

^q CHANG GUNG MEMORIAL HOSPITAL   (Taiwan)

^r UNIVERSITY OF CINCINNATI COLLEGE OF MEDICINE   (United States)

^s NATIONAL UNIVERSITY HOSPITAL   (Singapore)

^t University of Ulsan   (South Korea)

^u People's Hospital 115   (Viet Nam)

^v UNIVERSITY OF CALGARY   (Canada)

^w HOSPITAL DE CLÍNICAS DE PORTO ALEGRE   (Brazil)

^x UNIVERSITY OF SÃO PAULO   (Brazil)

^y Neurovascular Sciences Group   (Colombia)

^z USL Umbria 1   (Italy)

^aa CHRISTIAN MEDICAL COLLEGE   (India)

^ab JOHNS HOPKINS UNIVERSITY   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

ALTEPLASE; FIBRINOLYTIC AGENT; TISSUE PLASMINOGEN ACTIVATOR;

ADULT; AGED; ARTICLE; BLOOD PRESSURE REGULATION; BRAIN HEMORRHAGE; BRAIN ISCHEMIA; CONTROLLED STUDY; DISABILITY; DOSE RESPONSE; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG FATALITY; DRUG SAFETY; FEMALE; FIBRINOLYTIC THERAPY; HUMAN; LOW DRUG DOSE; MAJOR CLINICAL STUDY; MALE; MORTALITY; MULTICENTER STUDY; PRIORITY JOURNAL; PROSPECTIVE STUDY; RANDOMIZED CONTROLLED TRIAL; RANKIN SCALE; BLOOD PRESSURE; CHEMICALLY INDUCED; CLINICAL TRIAL; COMPARATIVE STUDY; DRUG EFFECTS; HYPERTENSION; INTRAVENOUS DRUG ADMINISTRATION; MIDDLE AGED; SINGLE BLIND PROCEDURE; STROKE; TREATMENT OUTCOME;

ADMINISTRATION, INTRAVENOUS; AGED; BLOOD PRESSURE; BRAIN ISCHEMIA; CEREBRAL HEMORRHAGE; FEMALE; FIBRINOLYTIC AGENTS; HUMANS; HYPERTENSION; MALE; MIDDLE AGED; SINGLE-BLIND METHOD; STROKE; TISSUE PLASMINOGEN ACTIVATOR; TREATMENT OUTCOME;

EID: 84974844136     PISSN: 00284793     EISSN: 15334406     Source Type: Journal    
DOI: 10.1056/NEJMoa1515510     Document Type: Article

References (28)

1. Emberson J, Lees KR, Lyden P, et al. Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials. Lancet 2014;384:1929-35.
2. Wardlaw JM, Murray V, Berge E, et al. Recombinant tissue plasminogen activator for acute ischaemic stroke: an updated systematic review and meta-analysis. Lancet 2012;379:2364-72.
3. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995;333:1581-7.
4. Yamaguchi T, Mori E, Minematsu K, et al. Alteplase at 0.6 mg/kg for acute ischemic stroke within 3 hours of onset: Japan Alteplase Clinical Trial (J-ACT). Stroke 2006;37:1810-5.
5. Toyoda K, Koga M, Naganuma M, et al. Routine use of intravenous low-dose recombinant tissue plasminogen activator in Japanese patients: general outcomes and prognostic factors from the SAMURAI register. Stroke 2009;40:3591-5.
6. Nakagawara J, Minematsu K, Okada Y, et al. Thrombolysis with 0.6 mg/kg intravenous alteplase for acute ischemic stroke in routine clinical practice: the Japan post-Marketing Alteplase Registration Study (J-MARS). Stroke 2010;41:1984-9.
7. Chao AC, Hsu HY, Chung CP, et al. Outcomes of thrombolytic therapy for acute ischemic stroke in Chinese patients: the Taiwan Thrombolytic Therapy for Acute Ischemic Stroke (TTT-AIS) study. Stroke 2010;41:885-90.
8. Kim BJ, Han MK, Park TH, et al. Low-versus standard-dose alteplase for ischemic strokes within 4.5 hours: a comparative effectiveness and safety study. Stroke 2015;46:2541-8.
9. Liao X, Wang Y, Pan Y, et al. Standard-dose intravenous tissue-type plasminogen activator for stroke is better than low doses. Stroke 2014;45:2354-8.
10. Wang Y, Liao X, Zhao X, et al. Using recombinant tissue plasminogen activator to treat acute ischemic stroke in China: analysis of the results from the Chinese National Stroke Registry (CNSR). Stroke 2011;42:1658-64.
11. Sharma VK, Ng KW, Venketasubramanian N, et al. Current status of intravenous thrombolysis for acute ischemic stroke in Asia. Int J Stroke 2011;6:523-30.
12. Menon BK, Saver JL, Prabhakaran S, et al. Risk score for intracranial hemorrhage in patients with acute ischemic stroke treated with intravenous tissue-type plasminogen activator. Stroke 2012;43:2293-9.
13. Huang Y, Sharma VK, Robinson T, et al. Rationale, design, and progress of the ENhanced Control of Hypertension ANd Thrombolysis strokE stuDy (ENCHANTED) trial: an international multicenter 2 x 2 quasi-factorial randomized controlled trial of low- vs. standard-dose rt-PA and early intensive vs. guideline-recommended blood pressure lowering in patients with acute ischaemic stroke eligible for thrombolysis treatment. Int J Stroke 2015;10:778-88.
14. Anderson CS, Woodward M, Arima H, et al. Statistical analysis plan for evaluating low- vs. standard-dose alteplase in the ENhanced Control of Hypertension and Thrombolysis strokE stuDy (ENCHANTED). Int J Stroke 2015;10:1313-5.
15. Quinn TJ, Dawson J, Walters MR, Lees KR. Functional outcome measures in contemporary stroke trials. Int J Stroke 2009;4:200-5.
16. Wahlgren N, Ahmed N, Dávalos A, et al. Thrombolysis with alteplase for acute ischaemic stroke in the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST): an observational study. Lancet 2007;369:275-82.
17. Bath PM, Lees KR, Schellinger PD, et al. Statistical analysis of the primary outcome in acute stroke trials. Stroke 2012;43:1171-8.
18. Rabin R, de Charro F. EQ-5D: a measure of health status from the EuroQol Group. Ann Med 2001;33:337-43.
19. Wardlaw JM, Murray V, Berge E, Del Zoppo GJ. Thrombolysis for acute ischaemic stroke. Cochrane Database Syst Rev 2009;4:CD000213.
20. Wardlaw JM, Murray V, Berge E, del Zoppo GJ. Thrombolysis for acute ischaemic stroke. Cochrane Database Syst Rev 2014;7:CD000213.
21. Howard G, Waller JL, Voeks JH, et al. A simple, assumption-free, and clinically interpretable approach for analysis of modified Rankin outcomes. Stroke 2012;43:664-9.
22. von Kummer R, Broderick JP, Campbell BCV, et al. The Heidelberg bleeding classification: classification of bleeding events after ischemic stroke and reperfusion therapy. Stroke 2015;46:2981-6.
23. Diener HC, Foerch C, Riess H, Röther J, Schroth G, Weber R. Treatment of acute ischaemic stroke with thrombolysis or thrombectomy in patients receiving antithrombotic treatment. Lancet Neurol 2013;12:677-88.
24. Whiteley WN, Slot KB, Fernandes P, Sandercock P, Wardlaw J. Risk factors for intracranial hemorrhage in acute ischemic stroke patients treated with recombinant tissue plasminogen activator: a systematic review and meta-analysis of 55 studies. Stroke 2012;43:2904-9.
25. Quinn TJ, Dawson J, Walters MR, Lees KR. Reliability of the modified Rankin Scale: a systematic review. Stroke 2009;40:3393-5.
26. Chaisinanunkul N, Adeoye O, Lewis RJ, et al. Adopting a patient-centered approach to primary outcome analysis of acute stroke trials using a utility-weighted modified Rankin scale. Stroke 2015;46:2238-43.
27. Sandercock P, Wardlaw JM, Dennis M, et al. Effect of thrombolysis with alteplase within 6 h of acute ischaemic stroke on long-term outcomes (the third International Stroke Trial [IST-3]): 18-month follow-up of a randomised controlled trial. Lancet Neurol 2013;12:768-76.
28. Saver JL, Fonarow GC, Smith EE, et al. Time to treatment with intravenous tissue plasminogen activator and outcome from acute ischemic stroke. JAMA 2013;309:2480-8.