Thrombolysis beyond the three-hour time window.

Abstract

Intravenous (i.v.) thrombolysis with tissue plasminogen activator (rt-PA, i.v. 0.9 mg/kg body weight) has been approved by European health authorities in 2002, with a 3-hr time window. The meta-analysis of i.v. rt-PA trials suggests efficacy of rt-PA up to 4.5 to 6 hr. However, treatment efficacy declines rapidly over time: the numbers of patients needed to treat to prevent 1 death or dependency are respectively 7, 12, and > 30 in the 0-3 hr, 0-6 hr, and 3-6 hr time windows. Magnetic resonance imaging may be the best way to select candidates for thrombolysis beyond 3 hr, on the basis of the presence of arterial occlusion and mismatch between diffusion and perfusion images. New trials are testing the possibility of extending the time window. Trials with new thrombolytic agents, ultrasound thrombolysis, and mechanical thrombolysis also are running or planned in the 3- to 6-hr time window. The 3-hr limit is just a matter of safety. Patients should be treated as soon as possible, and the earliest is the best.