The primary analysis of the European Cooperative Acute Stroke Study III (ECAS III) indicated that even when given outside the well established 3-hour treatment window (3 to 4.5 hours), alteplase reduces mortality relative to placebo. The goal of the current ECAS III analysis was to confirm a beneficial effect for alteplase using other endpoints and to examine outcomes in different patient subgroups.
As reported in the October 21st online issue of The Lancet Neurology, Dr. Werner Hacke, from the University of Heidelberg, Germany, and colleagues assessed functional outcomes in 418 patients randomized to receive alteplase (0.9 mg/kg) and 403 treated with placebo. The corresponding numbers of patients in the per-protocol analysis were 375 and 355.
In both intention-to-treat and per-protocol analyses, alteplase was associated with better outcomes than placebo. Although not all of the differences were statistically significant, there was always at least a trend toward better outcomes with alteplase.
The outcomes that were significantly better with alteplase included the modified Rankin scale score 0-1, the National Institutes of Health stroke scale score 0-1, and the Global outcome statistic.
Alteplase was found to be useful in men and women, over and under 65 years of age, and with or without a history of hypertension, stroke, or diabetes. Moreover, the drug was beneficial regardless of stroke severity.
The risk of symptomatic intracranial hemorrhage was significantly higher in patients 65 years of age and older. Previous antiplatelet drug use and time from onset of stroke symptoms to treatment, by contrast, had no bearing on the risk of this complication.
“I continue to be surprised at the sound and fury directed against thrombolytic therapy for stroke by some, but the publication of ECASS III, with the extended analyses published in this issue of the journal, reassures me,” Dr. Patrick D. Lyden, from Cedars-Sinai Medical Center, Los Angeles, writes in an editorial. “Thrombolytic therapy benefits patients, should be given as early as possible, offers sustained benefit, and is cost-effective.”
Lancet Neurol 2009.