New insights on thrombolytic treatment of acute ischemic stroke.

In 1995, a two-part randomized trial showed the efficacy of intravenous tissue plasminogen activator (tPA) when given within 3 hours of onset of symptoms of acute ischemic stroke. Two subsequent trials were unable to extend the therapeutic window of intravenous tPA beyond 3 hours. A phase IV study performed by experienced stroke centers showed an acceptably low symptomatic intracerebral hemorrhage rate for intravenous tPA of only 3%, whereas a review of the Cleveland area experience showed a disturbingly high rate of symptomatic intracerebral hemorrhage of 15.7%. The Prolyse in Acute Cerebral Thromboembolism (PROACT) II study showed efficacy of intra-arterial pro-urokinase and intravenous heparin over intravenous heparin alone when given within 6 hours of onset of symptoms to patients with thrombotic occlusion of the proximal middle cerebral artery. Additional controlled investigations of intra-arterial thrombolytic therapy are needed. Neuroprotectants in combination with intravenous tPA have yet to show improved efficacy over the use of tPA alone.