MedWire News: The treatment window for thrombolysis in acute ischemic stroke (AIS) can be extended to 4.5 hours, a new analysis of clinical trial data indicates.
In the ECASS III trial, patients who received alteplase up to 4.5 hours after the onset of stroke symptoms had better outcomes than patients treated with placebo, with the benefits of thrombolysis seen across a broad range of patient subgroups.
"Our results support the use of this thrombolytic drug in the extended period across a broad range of patient subgroups who meet the requirements of the European product label but miss the approved treatment window of 0-3 hours," write the study authors, led by Werner Hacke (University of Heidelberg), in the journal Lancet Neurology.
However, they add: "Even with these encouraging findings, the most important principle of acute stroke intervention should not be lost - ie, time remains critical and fast treatment still provides the greatest chance of recovery."
Hacke's group performed a post-hoc analysis of the European Cooperative Acute Stroke Study III (ECASS III), a multicenter, double-blind, randomized, placebo-controlled trial in which patients with AIS were randomly assigned to receive intravenous alteplase 0.9 mg/kg or placebo 3.0-4.5 hours after the onset of stroke symptoms.
As reported previously by MedWire, the main finding from ECASS III was that alteplase-treated patients were more likely to have a favorable outcome (modified Rankin scale [mRS] score 0-1) at 90 days than placebo-treated patients. Mortality was similar between the groups.
The new report confirms the superiority of alteplase versus placebo on additional endpoints, such as the likelihood of independence (mRS score 0-2 and Barthel Index score ≥85) and response (at least an 8-point improvement on the National Institutes of Health Stroke Scale score).
Hacke's team also investigated the effect of alteplase in predefined subgroups, finding that treatment was consistently beneficial irrespective of patients' age, gender, stroke severity at baseline, or history of diabetes, stroke, or high blood pressure.
In terms of safety, the risk for symptomatic intracranial hemorrhage in alteplase-treated patients seemed to be independent of previous antiplatelet drug use and time from onset of symptoms to treatment. However, the risk was significantly higher in patients aged 65 years and over compared with younger patients.
In an accompanying Comment article, Patrick Lyden (Cedars-Sinai Medical Center, Los Angeles, California) says the new data are "robust" and "substantially confirm the findings of the main ECASS III paper" in supporting a wider therapeutic window for thrombolysis.
He adds: "Any physician who chooses to treat patients between 3.0 and 4.5 hours after stroke onset should adhere carefully to the ECASS III exclusion and inclusion criteria, and do so without delay-the extended time window allows us to treat more patients but does not allow us to prolong the door-to-needle time, which must remain as close to 1 hour as possible."
MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2009
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ECASS III: Window opens wider for thrombolysis