The earlier within the recommended treatment window that intravenous thrombolytic therapy was administered, the better the outcomes following ischemic stroke, particularly among those with moderate symptoms initially, an observational study showed.
Treatment within 90 minutes of stroke onset was associated with an increased likelihood of having an excellent functional outcome -- defined as no significant disability with or without symptoms -- at 3 months compared with later treatment, but only among those with an NIH Stroke Scale (NIHSS) score of 7 to 12 (OR 1.37, 95% CI 1.11-1.70), according to , of Helsinki University Central Hospital, and colleagues.
Action Points
- This multicenter observational study demonstrated an association between very early IV thrombolysis and excellent functional outcome in stroke patients with moderate symptoms.
- Be aware that early thrombolysis had no clear benefit among those with severe symptoms at presentation.
Among those with milder strokes, however, administration of IV thrombolytics within 90 minutes was associated with greater odds of having no symptoms at 3 months (OR 1.51, 95% CI 1.14-2.01) in an analysis done "to overcome the possible ceiling effect from spontaneous better prognosis of patients with mild symptoms," the researchers reported online in .
It's been known for a long time that "the earlier that you can treat a patient with a stroke the better the outcome," according to James Grotta, MD, chairman of the neurology department at UT Health Science Center in Houston.
But there are barriers to quick treatment in the U.S. compared with Europe, Grotta told .
In Europe, physicians often ride in ambulances and are able to evaluate patients in the field, which allows thrombolytic therapy to be started as soon as the patients reach the hospital. In the U.S., treatment won't be started until patients are evaluated in the emergency department.
"So we have to do as we do on the battlefield," Grotta said. "That is, take the hospital to the patient. And if we could put CT scanners in the ambulances, which has now been shown to be feasible, then we can treat the patient on the scene and possibly get them treated within the first hour."
It has been established in prior studies that earlier IV thrombolytic treatment is associated with improved functional outcomes after an acute ischemic stroke, and a recommendation to administer treatment as quickly as possible -- -- has been incorporated into guidelines.
In a single-center study, Strbian and colleagues previously showed that IV thrombolytic therapy when given within 90 minutes, although the effect varied by stroke severity.
To explore the issue in a larger cohort of patients, they examined data on 6,856 patients (mean age 72) treated with IV thrombolytic therapy after an ischemic stroke collected prospectively from 10 European centers. None of the patients received additional treatments and 19% received thrombolysis 90 minutes or less from symptom onset.
An excellent 3-month outcome was defined as a modified Rankin scale score of 0 (no symptoms) or 1 (no significant disability despite some symptoms).
After adjustment for age, sex, baseline stroke severity, admission glucose level, and year of treatment, a shorter treatment time as a continuous variable was associated with a greater chance of having an excellent functional outcome (P<0.001).
Treatment within 90 minutes of stroke onset was associated with improved functional outcomes at 3 months in patients with moderate symptoms, but not in those with an NIHSS score less than 7 (OR 1.04, 95% CI 0.78-1.39) or in those with a score greater than 12 (OR 1.oo, 95% CI 0.76-1.32).
The lower rate of intracranial hemorrhage among those treated within 90 minutes compared with those treated later (14.8% versus 17.6%, P=0.027) might explain some of the benefit of very early treatment, according to the authors.
Also, it "may be explained by [the] predictive effect of NIHSS >10 on presence of proximal cerebral artery occlusion, and ," they wrote. "NIHSS >10 is also a common cut-off in patient selection for endovascular approaches."
And finally, they wrote, "another possible explanation is [the] higher proportion of cardioembolism and lower proportion of small vessel disease in patients with NIHSS >12."
There were no relationships between treatment within 90 minutes and mortality in the overall cohort or in the subgroups defined by stroke severity, in contrast to the prior single-center study by Strbian and colleagues.
"This may be because of the limited number of patients treated ultra-early in the current cohort," they wrote.
From the American Heart Association:
Disclosures
Strbian reported that he had no conflicts of interest. His co-authors reported relationships with Boehringer Ingelheim and Genzyme.
Primary Source
Stroke: Journal of the American Heart Association
Strbian D, et al "Ultra-early intravenous stroke thrombolysis: do all patients benefit similarly?" Stroke 2013; DOI: 10.1161/STROKEAHA.111.000819.