An Article published Online First and in the December edition of The Lancet Neurology adds further evidence to back the extension of the treatment window for stroke using alteplase to 4.5 hours. Currently, the drug is only licensed for use in the 0-3 hour window following stroke. The Article is written by Dr Werner Hacke, Department of Neurology, University of Heidelberg, Germany, and colleagues.
Previously published research from ECASS III has shown that alteplase leads to better outcomes than placebo in stroke patients in the 3.0-4.5 hour window post stroke. In this study, the authors did secondary analyses using different endpoints to confirm or refute the efficacy and safety outcomes in the primary analysis in ECASS III. They also looked for evidence of confounding factors or subgroups that might differentially affect treatment outcome.
418 patients were assigned to alteplase in the 3.0-4.5 hours window post stroke, and 403 to placebo. Although not significant in every case, all additional endpoints showed at least a clear trend in favour of alteplase. This included patients both over and under 65 years, men and women, and patients with or without a history of diabetes, stroke, or high blood pressure. Alteplase was also beneficial regardless of the severity of the stroke.
The authors conclude: "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 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 accompanying Reflection and Reaction Comment, Dr Patrick Lyden, Cedars-Sinai Medical Center, Los Angeles, CA, USA, says: "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."
Dr Werner Hacke, Department of Neurology, University of Heidelberg, Germany. T) +49 (0) 6221 56 82 11 E) werner.hacke@med.uni-heidelberg.de
Dr Patrick Lyden, Cedars-Sinai Medical Center, Los Angeles, CA, USA. T) +1 619 787 4111 E) lydenp@cshs.org
For full Article and Reflection and Reaction, see: http://press.thelancet.com/tlnaltecass.pdf
Journal
The Lancet Neurology