In response to a post by Dr Crippen about thrombolysis in stroke I'm posting a nice graph showing how the outcome of thrombolysis is very dependent on speed of treatment.
I believe that thrombolysis was approved by the FDA in 1996 after a single positive RCT (National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group 1995, NEJM 333) although other trials showed no benefit. There has been much scepticism about the benefits and criticism of the original study (there was a baseline imbalance in stroke severity but reanalysis suggests this does not strongly affect the results – Ingall et al 2004, Stroke 35).
Uptake has been slow due to fears about intracranial bleeding and only around 3% of stroke patients are eligible (.
The figure above is from The ATLANTIS, ECASS, and NINDS rt-PA Study Group (2004) Lancet 363. They performed an individual patient meta-analysis of alteplase (2775 patients, 6 RCTs) and found:
•Logistic regression adjusted OR for 'favourable outcome' varied with time to treatment
•Substantial rate of intracerebral haemorrhage 6% vs 1%
•No significant difference in mortality
NICE Guidance (2007) is:
•Alteplase within 3 hours of symptom onset
•Exclude intracranial haemorrhage by imaging (i.e. CT)
•Administration by stroke specialists in a specialist centre
•Not indicated for under 18 yrs or over 80 yrs
•0.9 mg / kg (max 90 mg) infused i.v. in 60 mins, with 10% administered as an initial i.v. bolus
•Costs e.g. 75 kg patient, 67.5 mg alteplase at £480 (<£4000/QALY)
Post-marketing surveillance shows that thrombolysis is of similar efficacy and safety when used outside of clinical trials (Wahlgren et al 2007, Lancet 369 - SITS-MOST trial).
There's also been a Cochrane Review with similar results (Wardlaw et al 2003).