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

To the Editor: I respect the opinion of Hoffman1 and others who have recently expressed concerns about the use of tissue plasminogen activator (tPA) in patients with ischaemic stroke. However, it is critical that these views do not dampen the enthusiasm for better stroke treatments. The Therapeutic Goods Administration recently approved tPA for ischaemic stroke patients with symptoms of less than 3 hours’ duration. This approval has catalysed collaboration between stroke units around Australia and may provide benefits to patients who do not receive tPA, by improving clinical pathways, as well as a more coordinated approach to treatment.

Internationally acclaimed Australian stroke experts have already rebutted the arguments of opponents of the National Institute of Neurological Disorders and Stroke (NINDS) trial, 2,3 and an independent reanalysis of the NINDS data showed tPA to be more effective than originally reported.4 It is time to stop bickering about the NINDS trial5 and move forward, by focusing on a collaborative effort between emergency departments and stroke teams. In the near future, there will surely be better data on new-generation thrombolytics and other agents; all will operate on similar “time is brain” protocols, as did the NINDS trial.

Obviously, more data would be useful, but when clinicians are faced with patients with acute stroke today they must give the patients and their families the facts about tPA, regardless of their personal opinion. These are best expressed in terms of the absolute risk reduction for disability seen in the NINDs trial. It is interesting to note the widespread discomfort with the 6.4% risk of intracerebral haemorrhage (half of which were fatal) in this trial of a “medical” therapy. Surgeons quote similar morbidity and mortality risks every day to patients undergoing procedures such as coronary artery bypass grafting. Additionally, many surgical procedures became established on much less solid evidence than the NINDs trial, and yet there is no outcry. For example, many thousands of carotid endarterectomies were performed before the publication of controlled-trial data.

In properly selected patients in expert hands, we now have a treatment that works. Its risks should not be underestimated, but should also be placed into context when compared with other powerful therapies for serious illnesses. Patients presenting with acute ischaemic stroke in Australia today have the chance to benefit from tPA, but future patients will benefit even more, partly because of the process that is being undertaken to institute pathways for using this drug.