The trials discussed above demonstrated either a nonsignificant or negative effect of treatment of ischemic strokes beyond the 3-hr window. Relatively few patients were able to present to the emergency room, undergo a CT scan, and receive evaluation and treatment by a neurologist within 3 hr. In the NINDS rtPA trial, 16,000 patients were screened for the total study population of 624 patients (15). This time-constraint problem, along with the advent of more advanced radiographic technologies, warranted questioning whether the time window for treatment of acute stroke could be expanded by local application of IA thrombolytics to the causative clot. IA application theoretically would increase the effectiveness of thrombolytics by increasing the local concentration at the site of the clot while decreasing the total amount used, thereby decreasing the hemorrhagic complication rate. This methodology appeared especially enticing for large strokes that were caused by occlusion of major cerebral vessels.
Starting in the early 1980s, many case series provided anecdotal evidence that IA application of thrombolytics could recanalize an occluded cerebral vessel (23-25), providing the groundwork for the first randomized clinical trial to test the efficacy and safety of IA thrombolytics.
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