Research published from ECASS III has suggested that alteplase leads to better outcomes than placebo in stroke patients in the 3.0 to 4.5 hour window after a stroke. An article published Online First and in the December edition of The Lancet Neurology reports additional evidence to back the extension of the treatment window for stroke using alteplase to 4.5 hours. At present, the drug is licensed only for use in the 0 to 3 hour window following a stroke. The article is the work of Dr Werner Hacke, Department of Neurology, University of Heidelberg, Germany, and colleagues.
The authors in this study carried out secondary analyses using different endpoints to validate or disprove the efficacy and safety outcomes in the primary analysis in ECASS III. In addition, they explored evidence of confounding factors or subgroups that might differentially influence treatment outcome.
A total of 418 patients were assigned to alteplase in the 3.0 to 4.5 hours window post stroke. Another 403 patients were assigned to placebo. Findings indicated that all additional endpoints showed at least a clear trend in favour of alteplase. However, results were not significant in every case. The study included patients both over and under 65 years from both genders, patients with or without a history of diabetes, stroke, or high blood pressure. Regardless of the severity of the stroke, Alteplase was also beneficial.
The authors write in conclusion: “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 h. Even with these encouraging findings, the most important principle of acute stroke intervention should, however, not be lost – ie, time remains critical and fast treatment still provides the greatest chance of recovery.”
In an associated comment, Dr Patrick Lyden, Cedars-Sinai Medical Center, Los Angeles, CA, USA, remarks: “Thrombolytic therapy benefits patients, should be given as early as possible, offers sustained benefit, and is cost-effective. The physician must, as always, diligently undertake a careful history and physical examination, look at the non-contrast brain CT scan carefully, and follow the appropriate protocol. All of these steps will result in substantial benefit to public health and will safely benefit many patients. But ‘time is brain’, and therapy must be given as soon as possible after the patient arrives – there is indeed not a moment to lose.”
“Stroke treatment with alteplase given 3•0 – 4•5 h after onset of acute ischaemic stroke (ECASS III): additional outcomes and subgroup analysis of a randomised controlled trial”
Erich Bluhmki, Ángel Chamorro, Antoni Dávalos, Thomas Machnig, Christophe Sauce, Nils Wahlgren, Joanna Wardlaw, Werner Hacke
DOI: 10.1016/S1474-4422(09)70264-9
Written by Stephanie Brunner (B.A.)