The safety of a controversial clot-busting drug has been investigated by researchers, who have shown a modified dosage can reduce serious bleeding in the brain and improve survival rates.
It is hoped the findings from the trial of more than 3,000 patients in 100 hospitals worldwide could change the way the most common form of stroke is treated globally.
“If we reduce the dose level, we maintain most of the clot busting benefits but with significantly less major bleeds”
Intravenous rtPA – or alteplase – is given to people suffering acute ischaemic stroke. However, it can cause serious bleeding in the brain in around 5% of cases, with many of these proving fatal.
The study, published in the New England Journal of Medicine, was conducted by the George Institute for Global Health and the University of Leicester.
Compared to standard dose (0.9mg/kg body weight), the lower dose (0.6mg/kg) of rtPA reduced rates of intracerebral haemorrhage by two thirds.
After 90 days, 8.5% of patients had died after receiving low dose rtPA, compared to 10.3% who received the standard dose.
The survival benefit was offset by a slight rise in the amount of people suffering residual disability.
“This new study will be welcome news for clinicians and patients”
For every 1,000 patients treated, low dose rtPA, compared to the standard dose, 41 more people had physical disabilities, such as needing help dressing or walking, but 19 fewer people died.
Lead study author Professor Craig Anderson said: “At the moment you could have a stroke but end up dying from a bleed in the brain. It’s largely unpredictable as to who will respond and who is at risk with rtPA.
“What we have shown is that if we reduce the dose level, we maintain most of the clot busting benefits of the higher dose but with significantly less major bleeds and improved survival rates,” he said.
“There is a trade off with the lower dose in regards to recovery of functioning, but being alive is surely preferable to most patients than suffering an early death,” he said.
Leicester’s Professor Tom Robinson said: “The results provide important information when discussing clot-busting treatment with patients and their families.
Researchers identify safer treatment regimen after stroke
“Most patients who have a major stroke want to know they will survive but without being seriously dependent on their family. We have shown this to be the case with the lower dose of the drug,” he said, adding that currently, around 11% of UK stroke patients receive thrombolysis treatment.
Dr Dale Webb, director of research and information at the Stroke Association, which helped fund the study, highlighted that an independent review in the UK concluded last year that the benefits of rtPA outweighed the risks.
“This new study will be welcome news for clinicians and patients, because it suggests that we can reduce the risk of bleeding with a lower dose of alteplase, whilst retaining most of its benefit,” he said.
The authors noted the differing effects meant that the trial was unable to show conclusively that the low dose was as effective as standard dose rtPA in terms of survivors being free of any disability.
Concerns over the risks of bleeding on the brain associated with rtPA have prompted independent reviews of the research evidence in Australia and the UK.