Consider thrombolysis in all stroke patients

MANY Australian stroke patients could be missing out on the most effective treatment available, with new research backing the use of intravenous thrombolysis in a wider range of patients.

Thrombolytic therapy with intravenous recombinant tissue plasminogen activator (rt-PA) is known to be of net benefit in acute ischaemic stroke patients younger than 80 years treated within 4.5 hours of onset.

However, two new research articles published in The Lancet suggest that a wider range of patients could benefit from the treatment.

The first, the largest study of thrombolysis to date by the International Stroke Trial (IST-3) collaborative group, assessed 3035 patients, including 53% aged over 80 years, at 156 hospitals in 12 countries, including Australia. It found that the treatment improved patients’ functional outcome and did not increase mortality. (1)

When patient outcome was assessed on a five-point scale ranging from no problems to very severe problems or death, patients treated with rt-PA had a 27% greater chance of surviving with less disability than those in the control group.

While rt-PA was associated with an increased risk of symptomatic haemorrhage and death in the first 7 days after treatment, fewer deaths were reported in the rt-PA group than in the control group between 7 days and 6 months, and by 6 months, similar numbers of patients had died in the two groups.

“The data add weight to the policy of treating patients as soon as possible, and also justify extending treatment to patients older than 80 years of age”, the authors wrote.

“The data do not support any restriction of treatment on the basis of stroke severity or the presence of early ischaemic change on the baseline brain scan.”

The second study, a meta-analysis combining the IST-3 trial results with other major trials on rt-PA, found that for every 1000 patients treated with intravenous rt-PA up to 6 hours after stroke, 42 more patients were alive and independent, and 55 more were alive with a favourable outcome at the end of follow-up. (2)

The study also found that among the 1711 patients older than 80 years, the absolute benefits from the treatment were a least as large as for the younger patients, especially with early treatment.

Professor Richard Lindley, a geriatrician from Westmead Clinical School and a coauthor of the second study, told MJA InSight that the uptake of thrombolysis was too low in Australia.

“People miss out because of delays in getting to hospital, within-hospital delays and sometimes reluctance to consider treatment. These new results from the IST-3 trial and the updated thrombolysis systematic review tell us that treatment can be extended to a wider group of people.

“Clinicians should be more confident that a wider group of people can be treated and hospitals need to change their practice to allow this to happen, and happen fast”, he said.

The authors of an accompanying comment in The Lancet wrote that the key message to emerge from the studies was that many patients currently excluded from treatment should now be candidates for treatment. (3)

They said the role of emergency physicians with stroke patients was now “not to identify patients who will be given rt-PA, but to identify the few who will not”.

Associate Professor Peter Hand, co-head of the acute stroke unit at Royal Melbourne Hospital, agreed, describing IST-3 as a landmark trial.

“In Australia, there is widespread variation in use of rt-PA. In some leading centres as many as 15% of patients with acute ischaemic stroke receive treatment. In many centres, no patients are treated”, he said.

He said there remained a small yet vocal group of clinicians who were sceptical of the benefits of rt-PA. “The results of IST-3 and the revised Cochrane Systematic Review should make these clinicians change their practice”, he said.

Although there were clear contraindications to treatment, such as finding haemorrhage on the CT scan, or a therapeutic INR, these were becoming fewer, Professor Hand said.

“Every patient who presents to hospital within 6 hours must be considered eligible for rt-PA until proven otherwise.”

- Amanda Bryan

1. Lancet 2012; Online 23 May
2. Lancet 2012; Online 23 May
3. Lancet 2012; Online 23 May

Posted 28 May 2012