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Head To Head

Do risks outweigh benefits in thrombolysis for stroke?

BMJ 2013; 347 doi: (Published 29 August 2013) Cite this as: BMJ 2013;347:f5215
  1. Simon G A Brown, professor in emergency medicine12,
  2. Stephen P J Macdonald, associate professor in emergency medicine13,
  3. Graeme J Hankey, Winthrop professor of neurology45
  1. 1School of Primary, Aboriginal and Rural Health Care, University of Western Australia, Perth, Australia
  2. 2Emergency Department, Royal Perth Hospital, Perth, WA 6847, Australia
  3. 3Emergency Department, Armadale Health Service, Armadale, WA 6992, Australia
  4. 4School of Medicine and Pharmacology, University of Western Australia
  5. 5Department of Neurology, Sir Charles Gairdner Hospital, Nedlands, Perth 6009, Australia
  1. Correspondence to: S G A Brown simon.brown{at}, G J Hankey graeme.hankey{at}

Simon Brown and Stephen Macdonald argue that patients with stroke should not be given thrombolysis outside clinical trials, but Graeme Hankey says the benefits are clear in carefully selected patients

Yes—Simon G A Brown and Stephen P J Macdonald

Emergency physicians are strong advocates of thrombolysis for myocardial infarction because a series of studies in large numbers of patients have clearly and consistently shown that the benefits outweigh the risks. Thrombolysis for stroke does not receive the same unanimous support because the risks are higher and the evidence of benefit is not yet convincing. Of 12 controlled trials on the use of alteplase (recombinant tissue plasminogen activator) for stroke, only two found a benefit as defined by primary outcome measures.1 2 Two were stopped early because of harm,3 4 and the remaining studies had negative findings. This pattern is typical for a treatment that does not work.

Evidence of harm is clear

Randomised controlled trials have consistently found that thrombolysis for stroke is associated with a higher risk of intracranial haemorrhage and early death compared with placebo. For alteplase, excess haemorrhages and deaths in the first seven days have been calculated to be 58 per 1000 cases treated (95% confidence interval 49 to 68) and 25 (11 to 39), respectively, although by 3-6 months death rates are similar whether treated with alteplase or not.5

Overall benefit is unclear

The critical question is whether there is any long term benefit from thrombolysis that outweighs the early hazard. A systematic review has found that giving alteplase within six hours of stroke reduces the composite outcome of death or dependency by 42/1000 people treated (95% confidence interval 19 to 66), with a greater effect if given within three hours (90/1000 people treated, 46 to 135).5 Nevertheless, there is persistent concern about the positive studies informing this meta-analysis.6 7 8

Patients randomised to placebo in the National …

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