Thrombolysis in ischaemic stroke

A Cochrane systematic review has been undertaken where studies were selected if they were randomised controlled trials that compared thrombolytic drugs with placebo or control treatment in patients with definite ischaemic stroke.Trials were excluded if the treatment or control group received another active treatment not factored into randomisation.

The systematic review concluded that thrombolytic treatment, in patients with acute ischaemic stroke, led to an increase in short term mortality and symptomatic or fatal intracranial haemorrhage, but led to a decrease in longer term death or dependence.

A British Heart Foundation Factfile states (2)

• the outcome of thrombolysis is much better if thrombolysis is gven at 1 hour post-stroke than if it is given at 3 hours, and between 3-5 hours post-stroke there may be a small benefit
• major complication of thrombolysis is haemorrhage within the infarct, and this is increased if blood pressure is uncontrolled. Therefore, blood pressure should be below 185/110 mmHg and drugs given to reduce blood pressure to below this threshold prior to administration of thrombolysis
• contraindications to thrombolysis include a history of intracranial haemorrhage, recent previous stroke or head trauma, major surgery or trauma in the last 14 days, a recent history of gastrointestinal haemorrhage or urinary tract bleeding, anad a history cerebra aneurysm or arteriovenous malformations
• before thrombolysis, the patient must have a CT scan to exclude haemorrhage

NICE (3,5) have stated that:

• alteplase is recommended for the treatment of acute ischaemic stroke when used by physicians trained and experienced in the management of acute stroke
• note that:
  • alteplase has a marketing authorisation for the fibrinolytic treatment of acute ischaemic stroke
  • alteplase is recommended within its marketing authorisation for treating acute ischaemic stroke in adults if:
    • treatment is started as early as possible within 4.5 hours of onset of stroke symptoms, and
    • intracranial haemorrhage has been excluded by appropriate imaging techniques
  • for further information about the drug refer to the summary of product characteristics

Notes:

• administration of thrombolysis after 3 hours
  • a study examined thrombolysis (intravenous alteplase) administered between 3 and 4.5 hours after the onset of a stroke (4)
    • authors concluded that, as compared with placebo, intravenous alteplase administered between 3 and 4.5 hours after the onset of symptoms significantly improved clinical outcomes in patients with acute ischemic stroke - however alteplase was more frequently associated with symptomatic intracranial hemorrhage
• tenecteplase has emerged as a potential alternative thrombolytic agent that might be preferred over alteplase because of its ease of administration and reported efficacy in patients with large vessel occlusion (6)

Reference:

1. Wardlaw JM. Overview of Cochrane thrombolysis meta-analysis. Neurology 2001 Sep;57(Suppl 2):S69-76.
2. BHF Factfile (December 2006). Early intervention in stroke.
3. NICE (September 2012).Alteplase for the treatment of acute ischaemic stroke
4. Hacke W et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke.N Engl J Med. 2008 Sep 25;359(13):1317-29
5. NICE (May 2019).Stroke and transient ischaemic attack in over 16s: diagnosis and initial management
6. Tsivgoulis G et al.Thrombolysis for acute ischaemic stroke: current status and future perspectives. Lancet Neurology March 9th 2003.