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Thrombolysis with intravenous (IV) tissue plasminogen activator (TPA) is an established treatment for patients with acute ischemic stroke. Previous analyses have found better outcomes associated with earlier TPA administration, up to 4.5 hours after symptom onset (Lancet 2010; 375:1695).
These investigators combined data from 10 European centers to determine whether “ultra-early” treatment (within 90 minutes after stroke onset) benefits all patients equally, regardless of baseline stroke severity. The 6856 patients were divided into groups by initial stroke severity score on the National Institutes of Health Stroke Scale (mild, 0–6 points; moderate, 7–12; severe, >12), and the researchers assessed their odds of achieving an excellent 3-month outcome (defined as a modified Rankin score of 0 to 1).
In the cohort as a whole, shorter time to treatment was associated with excellent neurologic outcome (P<0.001). Compared with later treatment, ultra-early thrombolysis was significantly associated with excellent outcome in patients with moderate baseline stroke severity, but not mild or severe stroke. The odds ratios for achieving an excellent outcome were 1.37 with moderate stroke (P=0.004); 1.00 with severe stroke (P=0.99); and 1.04 with mild stroke (P=0.80). There was no association between ultra-early treatment and mortality. Ultra-early treatment was associated with a decreased rate of overall brain hemorrhage but not symptomatic hemorrhage.
Strbian D et al. Ultra-early intravenous stroke thrombolysis: Do all patients benefit similarly? Stroke 2013 Aug 22; [e-pub ahead of print]. (http://dx.doi.org/10.1161/STROKEAHA.111.000819)
Comment
This study shows that the benefits of ultra-early thrombolysis are likely to be heterogeneous. Patients with moderate stroke showed the greatest improvement in outcomes with early treatment. Those with mild stroke have a shorter “distance to go” with regard to clinical improvement, so large numbers would be required to show a benefit. On the other hand, patients with severe stroke likely have a larger clot burden and may not respond as efficiently to IV thrombolysis. For severe stroke, improvement to a Rankin score of 0 to 2 may be a better index of recovery.
Importantly, this was not a randomized trial, and these data should not be used to guide treatment. Early thrombolytic administration is still better than late treatment.