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Mode of thrombolysis: Giving thrombolysis by infusion is an outdated approach.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”.

To the Editor: We applaud the call of Levi and his co-contributors for collegiate communication and consensus regarding the use of tissue plasminogen activator in acute ischaemic stroke.1 Emergency care providers are acutely aware of their role at the centre of the acute healthcare system. Daily, we interact with colleagues from other disciplines in the course of seeking the best clinical care for our patients.

However, the views expressed by Hoffman2 are shared by many emergency physicians and prehospital care providers. We remain unconvinced of the role of thrombolysis in acute ischaemic stroke outside the setting of properly constituted clinical trials.

On review of the contributors list in Levi’s article, we are unable to identify a single specialist emergency medicine or prehospital care provider. Consensus is not likely to be achieved until position statements from expert groups include a strong representation from all the specialty disciplines involved in the care of stroke patients. We look forward to developments in this direction.

In reply: We thank the authors for their comments on our recent position statement.1 We fully agree and accept the view of Rogers and colleagues that emergency physicians are central to the timely and safe delivery of emergency medical care in our health system. This is especially the case for a therapy such as intravenous tPA, given the narrow therapeutic window and coordination challenges. We view the development of linkages with our colleagues in emergency medicine as crucial in implementing not only tPA but also a number of acute stroke therapies showing great promise in the advanced stages of development.2 Our position statement is a starting point for broader discussion, and we are pleased that discussions between the key groups are under way.

We agree that, when considering patient suitability for intravenous tPA, a number of uncertainties remain, and we fully support the rationale for the ongoing clinical trials of thrombolysis in acute ischaemic stroke (see www.astn.org.au/epithet/index.html and www.ist3.com/). The risk–benefit ratio will be improved in the 0–90-minute window, as indicated by Fatovich. However, it is likely that some patients at much later time points will also gain benefit. We would emphasise, however, that according to Australia’s independent arbiter of therapeutic safety and efficacy, the Therapeutic Goods Administration, intravenous tPA is an approved therapy if given within a 3-hour window, under appropriate clinical circumstances and within appropriate healthcare settings.

Regarding the comments by Fatovich on number needed to harm, it is important to recognise that the most serious adverse outcome of intravenous tPA — fatal intracerebral haemorrhage — is already accounted for in the calculations of number needed to treat (for patients to survive free from dependency). Intra-arterial thrombolytic therapy in the form of prourokinase has been found to be effective in reducing dependency in acute ischaemic stroke, shown angiographically to be caused by middle cerebral artery occlusion.3 Feasibility issues, however, presently limit the application of the intra-arterial approach, and the relative risk of intracranial haemorrhage, even with this more targeted approach, is similar to that seen with intravenous therapy.

The importance of cross-disciplinary teamwork in the effective application of current and future acute stroke therapies cannot be underestimated. Central to this is the need to develop an effective dialogue between the leaders of these teams — stroke physicians and emergency physicians. The Australasian Stroke Unit Network, the New South Wales Greater Metropolitan Clinical Taskforce Stroke Initiative, and the Towards A Safer Culture Stroke Expert Working Group are committed to the task of helping to build better links between stroke units and emergency departments.