Tissue plasminogen activator (tPA) for acute ischaemic stroke: why so much has been made of so little

In reply: I agree with Blacker that enthusiasm generated by thrombolytic therapy could lead to benefit for stroke patients, independent of whether the therapy is actually useful, or even whether they receive it. However, I believe there are better ways to encourage rational stroke care.

I also acknowledge that some experts believe thrombolysis is proven to be beneficial if used in accordance with NINDS (National Institute of Neurological Disorders and Stroke) guidelines. Others believe the question is not yet settled and are concerned that widespread adoption of the guidelines will lead to more harm than good. It is one thing to enthuse about possible benefits of a treatment, particularly for a devastating disease for which we have traditionally had little to offer. It is entirely different to embrace this therapy, even though it may be harmful overall, simply out of this frustration.

I disagree with Blacker that the best way to inform patients about thrombolysis is “in terms of the absolute risk reduction for disability seen in the NINDS trial”. Regardless of concerns about the trial itself, it is always foolhardy to accept data from one small study as “the truth”. Many other trials have found far worse results — it would be equally inappropriate to base all estimates on their worst outcomes. Finally, there is strong evidence that, even if NINDS-like “success” could be achieved under optimal circumstances, routine use in the community might well lead to overall harm.

I am also cautious about Blacker’s comparison of thrombolysis and some surgical procedures in terms of adverse effect rates. No single adverse effect rate is or is not acceptable for all interventions — a 90% rate of intracerebral haemorrhage could be acceptable in a disease with 100% mortality, while a 2% rate would be completely unacceptable in a disease with no long-term morbidity. Furthermore, the adoption of many surgical interventions in the absence of persuasive evidence does not justify repeating this mistake.

Of course we must routinely make decisions without definitive evidence, based on our best estimates of benefits and harms. We should never take such decisions lightly, and should in general embrace the precautionary principle, which tells us not to adopt new therapies without reasonable evidence of their safety (especially when any benefit is likely to be extremely small).