The incidences of all-cause 90-day mortality, ICH, and new ischemic stroke following Activase treatment compared to placebo are presented in Table 4 as a combined safety analysis (n=624) for Parts 1 and 2. These data indicated a significant increase in ICH following Activase treatment, particularly symptomatic ICH within 36 hours. In Activase-treated patients, there were no increases compared to placebo in the incidences of 90-day mortality or severe disability.

Table 4
The NINDS t-PA Stroke Trial
Safety Outcome

In a prespecified subgroup analysis in patients receiving aspirin prior to onset of stroke symptoms, there was preserved favorable outcome for Activase-treated patients. Exploratory, multivariate analyses of both studies combined (n=624) to investigate potential predictors of ICH and treatment effect modifiers were performed. In Activase-treated patients presenting with severe neurological deficit (e.g., NIHSS > 22) or of advanced age (e.g., > 77 years of age), the trends toward increased risk for symptomatic ICH within the first 36 hours were more prominent. Similar trends were also seen for total ICH and for all-cause 90-day mortality in these patients. When risk was assessed by the combination of death and severe disability in these patients, there was no difference between placebo and Activase groups. Analyses for efficacy suggested a reduced but still favorable clinical outcome for Activase- treated patients with severe neurological deficit or advanced age at presentation.

Pulmonary Embolism Patients

In a comparative randomized trial (n=45),¹³ 59% of patients (n=22) treated with Activase (100 mg over 2 hours) experienced moderate or marked lysis of pulmonary emboli when assessed by pulmonary angiography 2 hours after treatment initiation. Activase-treated patients also experienced a significant reduction in pulmonary embolism-induced pulmonary hypertension within 2 hours of treatment (p=0.003). Pulmonary perfusion at 24 hours, as assessed by radionuclide scan, was significantly improved (p=0.002).

REFERENCES

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