Sue Ieraci: Thrombolytic truths

IT was reported last month that the Australian Competition and Consumer Commission (ACCC) had instituted claims against a NSW homeopath for posting allegedly misleading material on her website.

Most readers would agree that people making false or exaggerated claims about any therapeutic product should be held to account.

How well, then, do we apply those principles to our own practice? While we all support the principles of evidence-based practice (where appropriate evidence exists), are there areas where our own profession may be making claims beyond the evidence?

This made me look at the evidence, claims and evolving practice in the use of thrombolytic therapy for stroke.

While there is no comparison between the scientific principles of revascularisation and the anti-science of homeopathy, there is a common underlying principle. We need to be realistic with our claims and honest with our patients — and each other — about what the evidence actually shows.

Many of us remember the initial studies that established the place of thrombolysis in heart attack. The findings were reproduced over and over, and the evidence accumulated exponentially.

The criteria to thrombolyse were relatively straightforward, many people benefitted, and very few were significantly harmed.

It was natural that clinicians treating stroke — also a disease of vascular occlusion — would look for similar results to help their patients. While we know that stroke patients benefit in the long-term from admission to a specialised stroke unit, it makes sense to look for a more active and immediate therapy.

As interventional cardiology began to take over, thrombolytic therapy was looking for a new role.

So, what is the stroke thrombolysis research? Have the initial positive results been replicated in a huge database of strong evidence of benefit over harm?

Despite the trend for stroke thrombolysis to be seen by neurologists as a standard of care, the answer is, unfortunately, no.

A news article in MJA InSight last year illustrates the dilemma. The story, headed “Consider thrombolysis in all stroke patients”, reported on two papers in The Lancet suggesting that a wider range of stroke patients could potentially benefit from thrombolysis. It is in the readers’ comments on the article where critical commentary of the literature occurs.

The trial that first put stroke thrombolysis on the world stage was that by the National Institute of Neurological Disorders and Stroke, published in 1995. This work was not replicated in a major study until 2008, when the European Cooperative Acute Stroke Study (ECASS 3) was published.

ECASS 3 was a manufacturer-supported randomised controlled trial (RCT), with just over 800 patients enrolled. Despite randomisation, there were 5% more cases with severe stroke in the placebo group — which could account for the entire benefit found. Major symptomatic haemorrhages occurred in 2.4% of the thrombolysed group vs 0.2% of the placebo group.

To this point, nine of the 11 major acute stroke trials had demonstrated either no benefit or harm.

And what is the nature of the benefit? A study published in JAMA showed a small improvement in function at 30 days in patients administered thrombolysis between 3 and 5 hours after symptom onset (greatest in those with the mildest strokes), and no improvement in mortality (more in the thrombolysed group died in the early phase).

Therefore, to meet truth in advertising standards in 2013 thrombolysis in stroke requires this explanation: “There may be some long-term benefit from clot-busters in acute stroke but it’s not great. We don’t know which patients will benefit most, and who will die from it. It’s no miracle.”

Dr Sue Ieraci is a specialist emergency physician with 30 years’ experience in the public hospital system. Her particular interests include policy development and health system design, and she has held roles in medical regulation and management.

Posted 18 March 2013

Click here to read a news report on why experts are demanding a national strategy to improve stroke care, including wider use of thrombolysis