Neurology News

Follow our Neurology News blog for the latest news on neurologic diseases and research.

Friday, August 8, 2014

Early Treatment with Alteplase Leads to Better Patient Outcomes in Acute Ischemic Stroke

by Rebecca Hiscott


A new meta-analysis of stroke patients treated with alteplase (recombinant tissue plasminogen activator) shows that the clot-dissolving drug can significantly improve patient outcomes, especially when administered within three hours of symptom onset.


Computed tomographic appearance of acute ischemic stroke with intracerebral hemorrhage and subarachnoid hemorrhage.


The study, published in the August 6 online issue of The Lancet, looked at nine randomized clinical trials involving 6,756 patients with acute ischemic stroke, including 1,729 patients older than 80 years of age. In these trials, 787 patients were treated with alteplase within 3 hours of symptom onset, 1,275 received alteplase between 3 and 4.5 hours, and 1,229 were treated after more than 5 hours. The remaining patients received a placebo or open control.


“Our results show that alteplase treatment is a very effective means of limiting the degree of disability in stroke patients,” study co-author Jonathan Emberson, PhD, senior statistician at the University of Oxford’s Clinical Trial Service Unit, in the United Kingdom, said in a news release.


            Kennedy Lees, study co-author and professor of cerebrovascular medicine at the University of Glasgow, added that the treatment was most effective when administered within 3 hours of symptom onset. “What this shows is that we are up against the clock when treating ischemic stroke,” he said. “Every minute counts.”


            Patients who were given alteplase within 3 hours of symptom onset were 75 percent more likely to have a good outcome – defined as no significant disability after 3-6 months – than patients who were not treated with the drug. Those who received alteplase between 3 and 4.5 hours post-stroke saw their odds of a good outcome increase by 26 percent. Conversely, patients treated with alteplase more than 5 hours after symptom onset had improved odds of 15 percent, an increase that was not considered statistically significant. 


            “Alteplase significantly increased the odds of a good outcome, with earlier treatment resulting in significantly greater proportional benefit (p=0.016),” the authors wrote. “Proportional treatment benefits were similar irrespective of age or stroke severity,” they added.


The meta-analysis also sought to determine whether treatment with alteplase increased stroke patients’ risk of fatal intracranial hemorrhage, and found that risk of death by intracranial hemorrhage increased by 2 percent with intravenous alteplase treatment. The drug did not increase the risk of any other early causes of death, the authors noted.


            “Although alteplase increased the risk of death from intracranial hemorrhage by about 2 percent within the first few days after stroke, by a few months survivors treated with alteplase were less likely to be disabled than those not receiving such treatment,” Dr. Emberson said. “Indeed, alteplase increased the proportion who avoided disability altogether by about 10 percent for patients treated within three hours and 5 percent for those treated between three and four to five hours.”


            The findings could also impact current regulations governing alteplase treatment, the authors noted. For instance, US Food and Drug Administration has only approved the use of alteplase within 3 hours of symptom onset, while in some European nations, marketing of alteplase is restricted to patients younger than 80 years of age. However, the meta-analysis demonstrated that patients continue to benefit from alteplase treatment up to 4.5 hours after symptom onset, and also found that patients over the age of 80 treated with alteplase experienced the same improved outcomes as younger stroke patients.


            “Our results support guidelines that recommend use of alteplase irrespective of age and up to 4.5h after onset of stroke,” the authors concluded.


            For more coverage of alteplase treatment in stroke, browse our archives here: