Niaz Ahmed1, Karin Hermansson2, Erich Bluhmki3, Thierry Danays4, Ana Paiva Nunes5, Anthony Kenton6, Sekaran Lakshmanan7, Danilo Toni8, Robert Mikulik9, Gary A Ford10, Kennedy R Lees11, Nils Wahlgren1. 1. Department of Clinical Neuroscience, Karolinska Institutet and Department of Neurology Karolinska University Hospital, Stockholm, Sweden. 2. Boehringer Ingelheim Medical Department, Boehringer Ingelheim AB, Stockholm, Sweden. 3. Biostatistics, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany. 4. Medical Department, Boehringer Ingelheim France S.A.S., Reims, France. 5. Unidade CerebroVascular, Hospital de São José, Centro Hospitalar de Lisboa Central, Lisbon, Portugal. 6. University Hospitals Coventry and Warwickshire NHS Trust, UK. 7. Luton & Dunstable NHSFT University Hospital, Lewsey Road, Luton, UK. 8. Department of Neurology and Psychiatry, Sapienza University of Rome, Italy. 9. International Clinical Research Center and Neurology Department, St. Anne's Hospital in Brno, Czech Republic and Masaryk University, Brno, Czech Republic. 10. Medical Sciences Division, University of Oxford and Oxford University Hospitals NHS Foundation Trust, Oxford, UK. 11. Institute of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow, UK.
Abstract
INTRODUCTION: The SITS-UTMOST (Safe Implementation of Thrombolysis in Upper Time window Monitoring Study) was a registry-based prospective study of intravenous alteplase used in the extended time window (3-4.5 h) in acute ischaemic stroke to evaluate the impact of the approval of the extended time window on routine clinical practice. PATIENTS AND METHODS: Inclusion of at least 1000 patients treated within 3-4.5 h according to the licensed criteria and actively registered in the SITS-International Stroke Thrombolysis Registry was planned. Prospective data collection started 2 May 2012 and ended 2 November 2014. A historical cohort was identified for 2 years preceding May 2012. Clinical management and outcome were contrasted between patients treated within 3 h versus 3-4.5 h in the prospective cohort and between historical and prospective cohorts for the 3 h time window. Outcomes were functional independency (modified Rankin scale, mRS) 0-2, favourable outcome (mRS 0-1), and death at 3 months and symptomatic intracerebral haemorrhage (SICH) per SITS. RESULTS: 4157 patients from 81 centres in 12 EU countries were entered prospectively (N = 1118 in the 3-4.5 h, N = 3039 in the 0-3 h time window) and 3454 retrospective patients in the 0-3 h time window who met the marketing approval conditions. In the prospective cohort, median arrival to treatment time was longer in the 3-4.5 h than 3 h window (79 vs. 55 min). Within the 3 h time window, treatment delays were shorter for prospective than historical patients (55 vs. 63). There was no significant difference between the 3-4.5 h versus 3 h prospective cohort with regard to percentage of reported SICH (1.6 vs. 1.7), death (11.6 vs. 11.1), functional independency (66 vs. 65) at 3 months or favourable outcome (51 vs. 50). DISCUSSION: Main weakness is the observational design of the study. CONCLUSION: This study neither identified negative impact on treatment delay, nor on outcome, following extension of the approved time window to 4.5 h for use of alteplase in stroke.
INTRODUCTION: The SITS-UTMOST (Safe Implementation of Thrombolysis in Upper Time window Monitoring Study) was a registry-based prospective study of intravenous alteplase used in the extended time window (3-4.5 h) in acute ischaemic stroke to evaluate the impact of the approval of the extended time window on routine clinical practice. PATIENTS AND METHODS: Inclusion of at least 1000 patients treated within 3-4.5 h according to the licensed criteria and actively registered in the SITS-International Stroke Thrombolysis Registry was planned. Prospective data collection started 2 May 2012 and ended 2 November 2014. A historical cohort was identified for 2 years preceding May 2012. Clinical management and outcome were contrasted between patients treated within 3 h versus 3-4.5 h in the prospective cohort and between historical and prospective cohorts for the 3 h time window. Outcomes were functional independency (modified Rankin scale, mRS) 0-2, favourable outcome (mRS 0-1), and death at 3 months and symptomatic intracerebral haemorrhage (SICH) per SITS. RESULTS: 4157 patients from 81 centres in 12 EU countries were entered prospectively (N = 1118 in the 3-4.5 h, N = 3039 in the 0-3 h time window) and 3454 retrospective patients in the 0-3 h time window who met the marketing approval conditions. In the prospective cohort, median arrival to treatment time was longer in the 3-4.5 h than 3 h window (79 vs. 55 min). Within the 3 h time window, treatment delays were shorter for prospective than historical patients (55 vs. 63). There was no significant difference between the 3-4.5 h versus 3 h prospective cohort with regard to percentage of reported SICH (1.6 vs. 1.7), death (11.6 vs. 11.1), functional independency (66 vs. 65) at 3 months or favourable outcome (51 vs. 50). DISCUSSION: Main weakness is the observational design of the study. CONCLUSION: This study neither identified negative impact on treatment delay, nor on outcome, following extension of the approved time window to 4.5 h for use of alteplase in stroke.
Entities:
Keywords:
Actilyse; Stroke; haemorrhage; ischaemia; thrombolysis; time to treatment
Authors: Nils Wahlgren; Niaz Ahmed; Antoni Dávalos; Gary A Ford; Martin Grond; Werner Hacke; Michael G Hennerici; Markku Kaste; Sonja Kuelkens; Vincent Larrue; Kennedy R Lees; Risto O Roine; Lauri Soinne; Danilo Toni; Geert Vanhooren Journal: Lancet Date: 2007-01-27 Impact factor: 79.321
Authors: Kennedy R Lees; Erich Bluhmki; Rüdiger von Kummer; Thomas G Brott; Danilo Toni; James C Grotta; Gregory W Albers; Markku Kaste; John R Marler; Scott A Hamilton; Barbara C Tilley; Stephen M Davis; Geoffrey A Donnan; Werner Hacke; Kathryn Allen; Jochen Mau; Dieter Meier; Gregory del Zoppo; D A De Silva; K S Butcher; M W Parsons; P A Barber; C Levi; C Bladin; G Byrnes Journal: Lancet Date: 2010-05-15 Impact factor: 79.321
Authors: Gregg C Fonarow; Eric E Smith; Jeffrey L Saver; Mathew J Reeves; Adrian F Hernandez; Eric D Peterson; Ralph L Sacco; Lee H Schwamm Journal: Stroke Date: 2011-09-01 Impact factor: 7.914
Authors: Robert Mikulík; Pavla Kadlecová; Anna Czlonkowska; Adam Kobayashi; Miroslav Brozman; Viktor Svigelj; Laszlo Csiba; Klara Fekete; Janika Kõrv; Vida Demarin; Aleksandras Vilionskis; Dalius Jatuzis; Yakup Krespi; Niaz Ahmed Journal: Stroke Date: 2012-03-15 Impact factor: 7.914
Authors: Niaz Ahmed; Nils Wahlgren; Martin Grond; Michael Hennerici; Kennedy R Lees; Robert Mikulik; Mark Parsons; Risto O Roine; Danilo Toni; Peter Ringleb Journal: Lancet Neurol Date: 2010-07-26 Impact factor: 44.182
Authors: Werner Hacke; Markku Kaste; Erich Bluhmki; Miroslav Brozman; Antoni Dávalos; Donata Guidetti; Vincent Larrue; Kennedy R Lees; Zakaria Medeghri; Thomas Machnig; Dietmar Schneider; Rüdiger von Kummer; Nils Wahlgren; Danilo Toni Journal: N Engl J Med Date: 2008-09-25 Impact factor: 91.245
Authors: Nils Wahlgren; Niaz Ahmed; Antoni Dávalos; Werner Hacke; Mónica Millán; Keith Muir; Risto O Roine; Danilo Toni; Kennedy R Lees Journal: Lancet Date: 2008-09-12 Impact factor: 79.321
Authors: Werner Hacke; Geoffrey Donnan; Cesare Fieschi; Markku Kaste; Rüdiger von Kummer; Joseph P Broderick; Thomas Brott; Michael Frankel; James C Grotta; E Clarke Haley; Thomas Kwiatkowski; Steven R Levine; Chris Lewandowski; Mei Lu; Patrick Lyden; John R Marler; Suresh Patel; Barbara C Tilley; Gregory Albers; Erich Bluhmki; Manfred Wilhelm; Scott Hamilton Journal: Lancet Date: 2004-03-06 Impact factor: 79.321
Authors: Andria L Ford; Jennifer A Williams; Mary Spencer; Craig McCammon; Naim Khoury; Tomoko R Sampson; Peter Panagos; Jin-Moo Lee Journal: Stroke Date: 2012-11-08 Impact factor: 7.914
Authors: Peter Sandercock; Joanna M Wardlaw; Richard I Lindley; Martin Dennis; Geoff Cohen; Gordon Murray; Karen Innes; Graham Venables; Anna Czlonkowska; Adam Kobayashi; Stefano Ricci; Veronica Murray; Eivind Berge; Karsten Bruins Slot; Graeme J Hankey; Manuel Correia; Andre Peeters; Karl Matz; Phillippe Lyrer; Gord Gubitz; Stephen J Phillips; Antonio Arauz Journal: Lancet Date: 2012-05-23 Impact factor: 79.321