'Ultra-Early' Thrombolysis Cuts Disability in Mild Stroke

Megan Brooks

August 28, 2013

Giving intravenous (IV) tissue plasminogen activator (tPA) within 90 minutes was strongly and independently associated with excellent outcome in patients with mild to moderate acute ischemic stroke in a large 10-center European study.

The American Heart Association/American Stroke Association (AHA/ASA) recommends acute stroke patients arrive at the hospital within 3 hours of the onset of stroke symptoms. IV thrombolysis may be given up to 4.5 hours after the onset of symptoms.

The new study showed that survivors with mild to moderate stroke (National Institutes of Health Stroke Scale [NIHSS] score, 7 to 12) who received IV thrombolytic therapy in the first 90 minutes of the recommended time window had little or no disability 3 months later compared with those who were treated between 90 and 270 minutes.

"This paper tells us that early administration of clot-busting treatment to acute stroke patients is not good enough; we have to be ultra-early," first author Daniel Strbian, MD, PhD, associate professor, Department of Neurology, Helsinki University Central Hospital in Finland, told Medscape Medical News.

The study was published online August 22 in Stroke.

Early Treatment 'Not Good Enough'

In a telephone interview, Lee H. Schwamm, MD, national spokesperson for the AHA/ASA, noted that since the mid-1990s, the "real emphasis has been to increase the proportion of people who get treated. I think this study marks a new maturation in that campaign to say it's not enough to just treat, you have to treat as early as possible."

Dr. Schwamm wasn't involved in the study. He is vice chairman of the Massachusetts General Hospital, Neurology; director, Massachusetts General Hospital, Acute Stroke Services; professor of neurology, Harvard Medical School; and director, Partners TeleStroke Center, Massachusetts General Hospital, Boston.

In a prior single-center study published in Stroke in January 2010, Dr. Strbian and colleagues showed that "ultra-early" thrombolysis in acute ischemic stroke leads to better outcome and lower mortality. A pooled analysis of studies published in May 2010 showed similar findings, as reported by Medscape Medical News.

However, "not all patients benefit from early IV thrombolysis equally, say Dr. Strbian and colleagues in their latest report. Therefore, they explored whether the extra benefit of better outcome and lower mortality is distributed equally among predefined subgroups of stroke severity.

They used prospectively collected data on 6856 consecutive patients with acute ischemic stroke who received IV thrombolysis in 10 European stroke centers. In the whole cohort, shorter onset-to-treatment time (OTT) was significantly associated with excellent outcome (modified Rankin scale [mRS] score, 0 to 1; P < .001).

Almost 20% of all patients had OTT within 90 minutes, and these patients had lower frequency of intracranial hemorrhage. After adjustment for age, sex, admission glucose level, and year of treatment, OTT within 90 minutes was associated with excellent outcome in patients with mild/moderate stroke, but not in those with moderate to severe stroke or minor stroke.

Table. Adjusted Odds of Attaining mRS Score of 0 to 1 With OTT < 90 Minutes

Stroke Severity Odds Ratio (95% Confidence Interval)
Mild to moderate (NIHSS score, 7 to 12) 1.37 (1.11 - 1.70)
Moderate to severe (NIHSS score >12) 1.00 (0.76 - 1.32)
Minor (NIHSS score, 0 to 6) 1.04 (0.78 - 1.39)


The finding that patients with mild symptoms "seem to benefit less from ultra-early treatment may be explained by a ceiling effect from the spontaneously better prognosis," the researchers say.

In fact, when excellent 3-month outcome was set to an mRS score of 0, they did see an independent association of ultra-early thrombolysis in this subgroup of patients (odds ratio, 1.51; 95% confidence interval, 1.14 - 2.01; P < .01).

Unlike their previous study, they did not find any association of ultra-early thrombolysis with mortality. They think this may be due to the limited number of patients receiving ultra-early treatment in the current cohort.

For More Severe Stroke, Ultra-Early tPA Plus "Something Else"

The findings from this study "add to a growing literature that the benefits of early treatment are really substantial," Dr. Schwamm told Medscape Medical News.

"What I think is important about this paper," he added, "is it's from 10 European stroke centers, not just a single center, and it shows us that the patients who are most likely to respond to IV therapy are those with mild-to-moderate stroke."

"For the severe strokes, intravenous tPA alone really probably is not effective for most of those patients," Dr. Schwamm said. "For those patients, what we are going to need is ultra-early tPA plus something else. That something else is probably going to be a catheter-based treatment. Whether the newer generation of devices will finally give us what we hope, which is a rapid and effective reperfusion device, remains to be proven but looks very promising," Dr. Schwamm said.

Dr. Strbian and Dr. Schwamm have disclosed no relevant financial relationships. A complete list of author disclosures is provided with the original article.

Stroke. Published online August 22, 2013. Abstract


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.