The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the third international stroke trial [IST-3]): a randomised controlled trial

被引：924

作者：

Sandercock, Peter ^{[1
]}

Wardlaw, Joanna M.

Lindley, Richard I. ^{[2
,3
]}

Dennis, Martin

Cohen, Geoff

Murray, Gordon

Innes, Karen

Venables, Graham ^{[4
]}

Czlonkowska, Anna ^{[5
]}

Kobayashi, Adam

Ricci, Stefano ^{[6
]}

Murray, Veronica ^{[7
]}

Berge, Eivind ^{[8
]}

Slot, Karsten Bruins ^{[8
]}

Hankey, Graeme J. ^{[9
]}

Correia, Manuel ^{[10
]}

Peeters, Andre ^{[11
]}

Matz, Karl ^{[12
]}

Lyrer, Phillippe ^{[13
]}

Gubitz, Gord ^{[14
,15
]}

Phillips, Stephen J. ^{[14
,15
]}

Arauz, Antonio ^{[16
]}

Baigent, Colin ^{[17
]}

Chadwick, David ^{[18
]}

Tyrrell, Pippa ^{[19
]}

Lowe, Gordon

Farrall, Andrew

von Kummer, Rudiger

Cala, Lesley

von Heijne, Anders

Morris, Zoe

Adami, Alessandro

Potter, Gillian

Brady, Nick

Collins, Rory ^{[17
]}

Bath, Philip ^{[21
]}

van Gijn, Jan ^{[22
]}

Gray, Richard ^{[17
]}

Hart, Robert ^{[23
]}

Yusuf, Salim ^{[23
]}

Muir, Keith ^{[20
]}

Brainin, Michael

Engelter, Stefan

Terent, Andreas

Norrving, Bo

Wester, Per

Clark, Alison

Perry, David

Soosay, Vera

Buchanan, David

机构：

[1] Univ Edinburgh, Western Gen Hosp, Div Clin Neurosci, Crewe Rd, Edinburgh EH4 2XU, Midlothian, Scotland

[2] Univ Sydney, Westmead Hosp, Sydney Med Sch, Sydney, NSW 2006, Australia

[3] Univ Sydney, George Inst Global Hlth, Sydney, NSW 2006, Australia

[4] Sheffield Teaching Hosp NHS Fdn Trust, Sheffield, S Yorkshire, England

[5] Med Univ Warsaw, Warsaw, Poland

[6] Osped Citta Castello, Dept Neurol ASL1, Citta Di Castello, Italy

[7] Karolinska Inst, Stockholm, Sweden

[8] Oslo Univ Hosp, Oslo, Norway

[9] Royal Perth Hosp, Perth, WA, Australia

[10] Hosp Geral Santo Antonio, Oporto, Portugal

[11] Clin Univ St Luc, B-1200 Brussels, Belgium

[12] Landesklinikum Donaureg Tulln, Tulln, Austria

[13] Univ Basel Hosp, CH-4031 Basel, Switzerland

[14] Dalhousie Univ, Halifax, NS, Canada

[15] Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada

[16] Inst Nacl Neurol, Mexico City, DF, Mexico

[17] Univ Oxford, Oxford, England

[18] Univ Liverpool, Liverpool L69 3BX, Merseyside, England

[19] Univ Manchester, Manchester, Lancs, England

[20] Univ Glasgow, Inst Neurol Sci, Glasgow, Lanark, Scotland

[21] Univ Nottingham, Nottingham NG7 2RD, England

[22] Univ Utrecht, Utrecht, Netherlands

[23] McMaster Univ, Hamilton, ON L8S 4L8, Canada

[24] Radcliffe Infirm, Clin Trial Serv Unit, Oxford OX2 6HE, England

来源：

LANCET | 2012年 / 379卷 / 9834期

基金：

英国医学研究理事会; 新加坡国家研究基金会; 澳大利亚国家健康与医学研究理事会;

关键词：

CASE-FATALITY; STATISTICAL-ANALYSIS; RISK-FACTORS; CT; OXFORDSHIRE; MORTALITY; ALTEPLASE; DISEASE; IMPACT; BRAIN;

D O I：

10.1016/S0140-6736(12)60768-5

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background Thrombolysis is of net benefit in patients with acute ischaemic stroke, who are younger than 80 years of age and are treated within 4.5 h of onset. The third International Stroke Trial (IST-3) sought to determine whether a wider range of patients might benefit up to 6 h from stroke onset. Methods In this international, multicentre, randomised, open-treatment trial, patients were allocated to 0.9 mg/kg intravenous recombinant tissue plasminogen activator (rt-PA) or to control. The primary analysis was of the proportion of patients alive and independent, as defined by an Oxford Handicap Score (OHS) of 0-2 at 6 months. The study is registered, ISRCTN25765518. Findings 3035 patients were enrolled by 156 hospitals in 12 countries. All of these patients were included in the analyses (1515 in the rt-PA group vs 1520 in the control group), of whom 1617 (53%) were older than 80 years of age. At 6 months, 554 (37%) patients in the rt-PA group versus 534 (35%) in the control group were alive and independent (OHS 0-2; adjusted odds ratio [OR] 1.13, 95% CI 0.95-1.35, p=0.181; a non-significant absolute increase of 14/1000, 95% CI -20 to 48). An ordinal analysis showed a significant shift in OHS scores; common OR 1.27 (95% CI 1.10-1.47, p=0.001). Fatal or non-fatal symptomatic intracranial haemorrhage within 7 days occurred in 104 (7%) patients in the rt-PA group versus 16 (1%) in the control group (adjusted OR 6.94, 95% CI 4.07-11.8; absolute excess 58/1000, 95% CI 44-72). More deaths occurred within 7 days in the rt-PA group (163 [11%]) than in the control group (107 [7%], adjusted OR 1.60, 95% CI 1.22-2.08, p=0.001; absolute increase 37/1000, 95% CI 17-57), but between 7 days and 6 months there were fewer deaths in the rt-PA group than in the control group, so that by 6 months, similar numbers, in total, had died (408 [27%] in the rt-PA group vs 407 [27%] in the control group). Interpretation For the types of patient recruited in IST-3, despite the early hazards, thrombolysis within 6 h improved functional outcome. Benefit did not seem to be diminished in elderly patients.

引用

页码：2352 / 2363

页数：12

共 36 条

[1] A PROSPECTIVE-STUDY OF ACUTE CEREBROVASCULAR-DISEASE IN THE COMMUNITY - THE OXFORDSHIRE COMMUNITY STROKE PROJECT 1981-86 .2. INCIDENCE, CASE FATALITY RATES AND OVERALL OUTCOME AT ONE YEAR OF CEREBRAL INFARCTION, PRIMARY INTRACEREBRAL AND SUBARACHNOID HEMORRHAGE [J].