Patients Outside the 3hr Window

Although little controversy exists over the care of stroke patients presenting within 3 hr of symptom onset, patients beyond this window have increased rates of complications that bring into question the benefit of thrombolytics. Desmoteplase is the only intravenously administered thrombolytic to show improved functional outcome in patients who present >3 hr after onset of symptoms. The failure of the ECASS and ATLANTIS trials to show benefit has been largely attributed to the >3-hr time limit to administer thrombolytics. These findings beg the question: Should the 3-hr window be an absolute ceiling for administration of IV thrombolysis? A pooled analysis of ECASS I and II, the NINDS, and ATLANTIS trials, which addresses this issue, was recently published (45). Results of this analysis again clearly verified the safety and efficacy of thrombolysis within 3 hr from onset of symptoms and, in fact, showed possible efficacy up to 4.5 hr (Fig. 1), in addition to demonstrating a strong association between rapid treatment and favorable outcome.

One key to treating patients outside of the 3-hr window is to distinguish those who would benefit from reperfusion from those with no salvageable tissue who would only be exposed to the detrimental effects of administration of thrombolytics. Of these patients, better patient characterization is necessary to determine which method of revascularization would be best. The goal of the ongoing EPITHET trial is to determine whether the extent of the ischemic penumbra apparent on perfusion-diffusion MRI can be used to identify patients who would respond positively and safely to IV rtPA beyond 3 hr of stroke onset.

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