Giving a lower dose of clot-busting drugs to ischemic stroke patients reduced serious brain bleeding by two-thirds but led to a slight rise in ongoing disability, according to results of a study presented at the Second European Stroke Organization Conference 2016 in Barcelona, Spain.
The ENCHANTED study, led by Professor Craig Anderson of the George Institute for Global Health and University of Sydney, Australia, tested whether a lower dose of the intravenous rtPA (or alteplase) was safer and as effective as the dose currently used in patients with ischemic stroke. The drug is given to help break up blood clots blocking the flow of blood to the brain. However, it can cause serious bleeding in the brain in around 5% of cases, with many of these proving fatal.
Investigators randomly assigned 3,310 ischemic stroke patients who were eligible for thrombolytic therapy (median age, 67 years; 63% Asian) to low-dose intravenous alteplase (0.6 mg/kg) or the standard dose (0.9 mg/kg); patients underwent randomization within 4.5 hours after the onset of stroke. The primary objective was to determine whether the low dose would be noninferior to the standard dose with respect to the primary outcome of death or disability at 90 days.
Death or disability occurred in 855 of 1,607 participants (53.2%) in the low-dose group and in 817 of 1,599 participants (51.1%) in the standard-dose group (odds ratio, 1.09; 95% confidence interval [CI], 0.95–1.25; P = 0.51 for noninferiority). Major symptomatic intracerebral hemorrhage occurred in 1.0% of the participants in the low-dose group and in 2.1% of the participants in the standard-dose group (P = 0.01).
Low-dose treatment reduced serious brain bleeding by two-thirds; it also reduced death at 90 days (from 10.3% to 8.5%), although the difference was not statistically significant. For every 1,000 patients treated with low dose rtPA, 19 fewer people died; however, 41 more people had physical disabilities, such as needing help dressing or walking.
The study was published online in The New England Journal of Medicine.
The trial did not meet the standard for the noninferiority of low-dose alteplase to standard-dose alteplase with respect to death and disability at 90 days. Still, Anderson said he hoped the lower dose would become the standard in situations where a doctor considers the risk of cerebral hemorrhage to be high in a particular patient.
"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,” Anderson said. “On a global scale, this approach could save the lives of many tens of thousands of people."