Time is brain: Post-marketing experience with alteplase (tPA) for acute ischemic stroke

Thrombolytic therapy with alteplase (tPA; Activase(®)) has been approved in the U.S. and Canada for use in the treatment of acute ischemic stroke (AIS). Based on the results of five Phase III clinical trials, administration of alteplase is limited to those patients presenting for treatment within 3 hours after initial onset of stroke symptoms. Published post-marketing experience with alteplase has been reported in over 1,000 patients, largely from investigative centers that have previously participated in the randomized clinical trials. This study population will soon be expanded three-fold, with the publication of post-marketing data from two ongoing collaborations, the multicenter tPA Stroke Survey and the Canadian Activase for Stroke Effectiveness Study (CASES). Initial clinical data in CASES from over 600 treated patients have been very favorable, with 31% achieving an excellent neurological outcome and a rate of symptomatic intracranial hemorrhage of only 4%. However, open clinical experience with alteplase does not appear to demonstrate the same degree of therapeutic efficacy as in the randomized trials, particularly in community hospital settings. This is likely due to alteplase being administered later during the 3-hour post-stroke treatment window, less uniform patient selection, and the difficulties typically experienced in applying complex technologies to clinical practice. An overwhelming majority of the published reports on post-marketing experience with alteplase in stroke have been positive, and hundreds of stroke patients have benefited from this treatment. However, physicians, hospitals and the lay public must be more aggressively educated about acute stroke care, and stroke teams must be more widely established, in order to ensure the most effective application of thrombolysis with the use of alteplase in AIS.