Alteplase does not appear to benefit patients with mild acute ischaemic stroke presenting with initially minor neurologic deficits.
The findings, from the prematurely terminated PRISMS trial, support current practice and should help reassure clinicians in managing this sub-group of stroke patients with a low NIH Stroke Scale score and non-disabling symptoms.
The data, from the first 313 patients enrolled into the trial, showed no difference in functional outcome between patients randomised to intravenous alteplase plus placebo oral aspirin (0.9mg/kg) versus oral aspirin alone.
About 78% of alteplase-treated patients had a favourable functional outcome on a modified Rankin Scale compared to 81% on aspirin.
Intracranial haemorrhage, the primary adverse event, occurred in five patients given alteplase (3.2%) but in none of the aspirin only patients.
Professor Alan Barber, a stroke specialist at the University of Auckland, said the study was compromised by its early termination but was still useful.
“The study stopped with only a third of the planned 900 patients and looking at the results there was no difference between aspirin and alteplase.”
“They also looked at how good would alteplase have to be in the remaining 600 patients if included in the study and they came up with the conclusion that it was unlikely that alteplase was ever going to be better than aspirin.”
“The signal this study gave was that we shouldn’t be using alteplase in people who have mild, non-disabling symptoms. It doesn’t mean that we shouldn’t use alteplase in patients with a low NHI Stroke Scale score but disabling symptoms which is what we are doing.”
Professor Barber said recent findings from the POINT trial suggested the most effective treatment was aspirin in combination with clopidogrel for three weeks.
An editorial in JAMA said that it was unlikely the premature termination of the PRISMS trial influenced the failure to demonstrate a benefit with alteplase.
“The PRISMS trial helps define the role of intravenous alteplase in the management of acute ischaemic stroke. Even with early study termination and resultant wide 95% confidence intervals, the excellent outcomes in the aspirin group and the numerically similar outcomes between the two groups render it unlikely that intravenous alteplase treatment meaningfully improves functional outcome in patients with initial NIHSS scores of 5 or lower with non-disabling symptoms.”