Analysis Supports 4.5-Hour Alteplase Treatment Window

October 20, 2009—The Lancet Neurology announced the publication online ahead of print of findings from the ECASS III (European Cooperative Acute Stroke Study III) by Werner Hacke, MD, et al that add to the evidence to back the extension of the treatment window for stroke using alteplase recombinant tissue plasminogen activator to 4.5 hours. Currently, the drug is approved for use in the 0- to 3-hour window after a stroke.

According to The Lancet Neurology, previously published research from ECASS III has shown that alteplase leads to better outcomes than placebo in stroke patients in the 3- to 4.5-hour period after a stroke. In this study, the investigators conducted 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 the treatment outcome.

The investigators reported that 418 patients were assigned to alteplase in the 3- to 4.5-hour window after a stroke, and 403 patients were assigned to placebo. Although not significant in every case, all additional endpoints showed at least a clear trend in favor of alteplase. This included patients both older and younger than 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 investigators concluded that these results support the use of this thrombolytic drug in the extended period across a broad range of subgroups of patients who meet the requirements of the European product label but miss the approved treatment window of 0 to 3 hours.

The investigators stated, “Even with these encouraging findings, the most important principle of acute stroke intervention should not be lost—time remains critical, and fast treatment still provides the greatest chance of recovery.”

In an accompanying “Reflection and Reaction” commentary, Patrick Lyden, MD, stated:

“Thrombolytic therapy benefits patients, should be given as early as possible, offers sustained benefit, and is costeffective. The physician must, as always, diligently undertake a careful history and physical examination, look at the noncontrast brain computed tomography 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.”