Intended for healthcare professionals


Thrombolysis in acute ischaemic stroke: time for a rethink?

BMJ 2015; 350 doi: (Published 17 March 2015) Cite this as: BMJ 2015;350:h1075
  1. Brian S Alper, vice president of evidence based medicine research and development, quality and standards 1,
  2. Meghan Malone-Moses, associate managing editor1,
  3. James S McLellan, associate managing editor1,
  4. Kameshwar Prasad, professor and head2,
  5. Eric Manheimer, Cochrane review author3
  1. 1DynaMed, EBSCO Health, EBSCO Information Services, Ipswich, MA 01938, USA
  2. 2Department of Neurology, All India Institute of Medical Sciences, New Delhi, India
  3. 3Bahrain Branch of the Cochrane Collaboration, Awali, Bahrain
  1. Correspondence to: B S Alper balper{at}
  • Accepted 18 February 2015

As the UK regulator reviews alteplase in ischaemic stroke, Brian Alper and colleagues interpret the evidence to suggest increased mortality with uncertain benefit for its use beyond three hours

Systematic reviews and guidelines conclude that thrombolysis with alteplase (t-PA) up to 4.5 hours after the onset of ischaemic stroke is beneficial. It is reported to increase the likelihood of being functionally independent and not increase the 90 day risk of mortality. In the US the licence, or marketing authorisation, for alteplase is limited to 0-3 hours after onset of stroke,1 but some other countries—including the UK and Australia—have extended the licence to 4.5 hours.2 3 4 Irrespective of licensing, most major stroke guidelines support use of alteplase up to 4.5 hours after stroke onset,5 6 7 8 9 10 11 12 13 14 15 16 although several emergency medicine associations do not recommend it (box).17 18 19 20 21

Major stroke guidelines and recommendations for alteplase at 3-4.5 hours after stroke onset

Guidelines presenting strong recommendation for (“is recommended” or highest recommendation rating)
  • American Heart Association/American Stroke Association (Class I; Level of evidence B)5

  • Canadian Stroke Network and Heart and Stroke Foundation of Canada (Evidence level A)6

  • Chinese Stroke Therapy Expert Panel for Intravenous Recombinant Tissue Plasminogen Activator (Level 1 recommendation, Level A evidence)7

  • European Stroke Organisation (Class I, Level A)8

  • Haute Autorité de Santé (Professional agreement)9

  • Japan Stroke Society (level of evidence Ia; grade of recommendation A)10

  • National Institute for Health and Care Excellence (“is recommended”)11

  • National Stroke Foundation (Australia) (Grade A)12

  • South African Stroke Society (Class I, Level A)13

Guidelines presenting weak recommendation for (lower recommendation rating)
  • American College of Chest Physicians (Grade 2C)14

  • American College of Emergency Physicians/American Academy of Neurology (Level B recommendation), currently being reconsidered by American College of Emergency Physicians15

  • American College of Emergency Physicians (draft guideline in process) (Level B recommendation)16

Guidelines presenting weak recommendation against
  • Canadian Association of Emergency Physicians (draft guideline in …

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