This study found no significant rt-PA benefit on the 90-day efficacy end points in patients treated between 3 and 5 hours. The risk of symptomatic ICH increased with rt-PA treatment. These results do not support the use of intravenous rt-PA for stroke treatment beyond 3 hours.

Background and Purpose-Patient delays in seeking treatment for stroke and delays within the Emergency Department (ED) are major factors in the lack of use of thrombolytic therapy for stroke. The Genentech Stroke Presentation Survey was a multicentered prospective registry of patients with acute stroke. The study was designed to characterize prehospital delays and delays within the ED. Methods-Patients with stroke symptoms presenting to 48 EDs participating in a clinical trial of acute stroke therapy were enrolled prospectively. A 1-page data form was completed from patient interviews and medical records. Results-A total of 1207 subjects were entered into the study. Ninety-four percent of the 721 subjects with complete data had a diagnosis of stroke or transient ischemic attack, 13% were black, 50% were female, and 67% were aged Ͼ65 years. The median time from symptom onset to ED arrival was 2.6 (interquartile range 1.2 to 6.3) hours. The median time from ED arrival until CT scan completion was 1.1 (0.7 to 1.8) hours, and the total delay time (symptom onset until CT scan completion) had a median of 4.0 (2.3 to 8.3) hours. Patients who arrived by emergency medical services had significantly shorter prehospital delay times and times to CT scan. Age, race, sex, and educational level did not appear to affect prehospital delay times. Conclusions-Despite its limitations, this large geographically diverse study strongly suggests that the use of emergency medical services is an important modifiable determinant of delay time for the treatment of acute stroke. (Stroke. 2000;31:2585-2590.)

This study found no significant rtPA benefit on any of the planned efficacy end points at 30 and 90 days in patients treated between 0 and 6 hours after stroke onset. These negative results apply to patients treated after 3 hours, because only 15% of the patients were enrolled before 3 hours. The risk of symptomatic intracerebral hemorrhage was increased with rtPA treatment, particularly in patients treated between 5 and 6 hours after onset. These results do not support the use of intravenous rtPA for stroke treatment >3 hours after onset.

Rapid identification of stroke subtype is valuable for both practicing clinicians and the optimal design of clinical stroke trials. Mechanisms of ischemic injury might differ among different stroke subtypes. Certain subtypes might be clinically identified as suboptimal for future therapeutic or prophylactic stroke trials. Some subtypes might be so clinically distinct that extensive laboratory investigation is unwarranted. Investigators in the ongoing Trial of ORG 10172 in Acute Stroke Treatment are using criteria to categorize stroke etiology among enrolled patients into one of five subtypes: large-artery atherothromboembolic, cardioembolic, small-vessel thrombotic, other etiology, or undetermined etiology. As part of the study, physicians initially predict the most likely subtype of stroke based on clinical features and baseline CT. Three months after stroke, investigators use the criteria, which also incorporate results of diagnostic testing, to reclassify stroke subtype. Initial clinical impression of subtype agreed with final determination in 62% of patients, and the rate was similar for all stroke subtypes. No stroke subtype was more accurately diagnosed than others by initial assessment. No subtype was more commonly identified by diagnostic studies. Fifteen percent of patients remained without a clear etiologic subtype diagnosis at 3 months. We conclude that clinical trials in stroke should not attempt to restrict entry into trials based on presumed stroke subtype. A careful evaluation for etiology is justified in all patients presenting with stroke, regardless of presumed subtype.