Tissue plasminogen activator (tPA) in acute ischaemic stroke: time for collegiate communication and consensus

To the Editor: I have read with interest the debate in the MJA on the use of tPA in acute ischaemic stroke. Most recently, Levi et al published a position statement stating that it is a major advance.1 This was probably in response to Hoffman’s critical editorial.2

At the 10th International Conference on Emergency Medicine in June 2004, a session on the use of tPA in acute ischaemic stroke clearly portrayed thrombolysis as not standard care.3 I have attended other emergency medicine conferences where thrombolysis was seen as risking more harm than good. Conversely, I expect that stroke physicians attend stroke conferences that endorse thrombolysis.

In my experience, when such divergent views exist, it usually means that we don’t have enough answers. I would like to outline here some other viewpoints that are not often considered.

Number needed to harm (NNH): The best results to date were from the NINDS study that reported a number needed to treat (NNT) of 8.4 With their findings of an intracranial haemorrhage rate of 6.4%, the NNH is about 16. Hence, for every 16 patients treated with tPA, two may derive much benefit, but one much harm. These odds are worse than Russian roulette. The Cleveland study reported an intracranial haemorrhage rate of 22%.5 Hence, the worst possible NNH is about 5. Other authors have expressed similar ethical concerns.6

Risk tolerance is an individual judgement, but, when faced with the above issues, my practice is to ask what I would want for myself. Knowing that the earlier thrombolysis is given the better,7 my personal choice would be to only have thrombolysis if it is administered within 90 minutes of stroke onset (ie, maximal benefit and minimal risk). Unfortunately, it is rare for patients to present early enough for this to occur. Furthermore, many of my colleagues do not know what they would want for themselves, so how can we advise our patients?

Pathophysiology: Heart muscle is relatively robust, whereas the brain is a softer structure. A haemorrhagic complication is very different in the two organs.

Mode of thrombolysis: Giving thrombolysis by infusion is an outdated approach. Furthermore, thrombolysis is almost a forgotten therapy for acute myocardial infarction in tertiary centres because of the use of primary angioplasty. When thrombolysis is used, the agent is given as a bolus. Uptake of this mode of administration would be rapid if it were shown to be effective and safe for acute ischaemic stroke.

Obviously, consensus among care providers on the use of tPA does not exist. This means that more research needs to be done to work out the answers to these difficult questions. I believe there is much support for this, as we need to define who should be receiving thrombolysis, and, perhaps more importantly, who should not. We all want something that works! However, we need greater knowledge to overcome the safety issues. The answer to Levi’s question “Why did it take so long?” is “Because it is a complex problem”.