Stroke a Race Against the Clock, Review Confirms

Megan Brooks

August 28, 2014

A large review of individual-patient data confirms the importance of providing rapid thrombolytic therapy in cases of acute ischemic stroke.

Irrespective of age or stroke severity, administration of alteplase within 4.5 hours of stroke onset significantly improves the likelihood of a good outcome (modified Rankin score of 0 or 1 indicating little or no residual disability at 3 to 6 months), with earlier treatment providing greater benefits, the researchers found.

"Our results show that alteplase treatment is a very effective means of limiting the degree of disability in stroke patients," Jonathan Emberson, PhD, study coauthor and senior statistician at the University of Oxford's Clinical Trial Service Unit in the United Kingdom, said in a statement.

Kennedy Lees, MD, study coauthor and professor of cerebrovascular medicine at the University of Glasgow, United Kingdom, added, "What this shows is that we are up against the clock when treating ischemic stroke. Every minute counts. People need to be identified quickly and systems need to be in place to get them scanned, diagnosed accurately, and then treated within minutes to hours."

The analysis was published online August 6 in The Lancet. The meta-analysis was also discussed earlier this year at the American Stroke Association International Stroke Conference 2014 and reported by Medscape Medical News at that time.

Clear Information

The study team assessed the effect of treatment delay, age, and stroke severity on the effect of intravenous thrombolysis with alteplase in 6756 patients with acute ischemic stroke who participated in 9 major trials of thrombolysis for treatment of stroke.

They found that the odds of a good stroke outcome were 75% greater for patients who received alteplase within 3 hours of symptom onset compared with those who did not receive the drug; for those given alteplase 3 to 4.5 hours after onset, there was a 26% increased chance of a good outcome; and those with a delay of more than 4.5 hours in receiving treatment had a non–statistically significant 15% increase in the chance of a good recovery.

The proportional treatment benefits of thrombolytic therapy were similar regardless of age or stroke severity. Of the 6756 patients in the studies, 1729 (25.6%) were older than 80 years of age.

"These new results tell us that the elderly should be treated with the same urgency as younger patients," Richard Lindley, MD, coauthor and professor of geriatric medicine at the University of Sydney in Australia, said in the statement.

The authors note that treatment with alteplase increased the risk for death from intracranial hemorrhage by about 2% within the first few days after stroke. However, by 3 to 6 months, this risk was offset by an average absolute increase in disability-free survival by about 10% for patients treated within 3 hours of onset and about 5% for those treated up to 4.5 hours after onset.

"I cannot overemphasise how useful these analyses are—they provide the type of clear information that patients and their families need when weighing the benefits and risks of this important treatment," Peter Sandercock, MD, professor of neurology, University of Edinburgh, United Kingdom, added in the statement.

Label "Obsolete"

In a linked comment, Michael Hill, MD, and Shelagh Coutts, MD, from the Hotchkiss Brain Institute and Department of Clinical Neurosciences, Calgary, Alberta, Canada, say the data "render obsolete" the European licensing label for alteplase, which excludes patients older than age 80 and those with severe stroke.

In addition, they say the finding of a small benefit of treatment up to 4.5 hours from onset makes the advice of the US Food and Drug Administration and Health Canada to not treat patients after 3 hours from onset "similarly outdated."

Dr. Hill and Dr. Coutts say the question now is not whether to extend the window for treatment, but rather how to get everyone treated faster and how to dispel preconceived notions about not treating older patients or those with milder strokes.

"Audits show that patients with ischemic stroke are offered thrombolysis too rarely or, if they are offered it, too slowly," they point out. "Quick treatment requires efficient processes and a team approach. Pre-hospital systems to identify patients and bring them to the appropriate hospitals, emergency department swarming, rapid simple imaging, and use of telemedicine must be harnessed to reduce times to treatment. Strategies to do so will vary by region but it is simply unacceptable not to achieve very fast treatment times," Dr. Hill and Dr. Coutts conclude.

The study was funded by the UK Medical Research Council, British Heart Foundation, University of Glasgow, and University of Edinburgh. A complete list of author disclosures is listed with the article.

Lancet. Published online August 6, 2014. Abstract Comment


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