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Safety results from the NINDS pivotal study

  • 6.4% incidence of SICH within first 36 hours. Significantly higher than among placebo patients (0.6%, P<0.001)4
  • All thrombolytic agents increase the risk of bleeding, including intracranial bleeding, and should be used only in appropriate patients
  • Not all patients with acute ischemic stroke will be eligible for Activase therapy, including patients with evidence of recent or active bleeding
    • – Recent (within 3 months) intracranial or intraspinal surgery, serious head trauma, or previous stroke
    • – Uncontrolled high blood pressure
    • – Or impaired blood clotting
  • Please see accompanying full prescribing information for additional safety information

In acute ischemic stroke —
Safety profile established by a wide range of studies1-3

SICH in clinical practice

Adapted from Graham GD. Stroke. 2003;34:2847; Katzan IL, et al. Stroke. 2003;34:799-800; and Wahlgren N. et al. Lancet. 2007;369:275.

The Cleveland (2000) study evaluated 29 area hospitals. Cleveland Clinic Health System (CCHS) studies later evaluated a subset of 9 hospitals. The NINDS and CCHS results are not factored into the overall 5.2% rate of SICH in "ABOVE STUDIES."

  • *
  • Symptomatic intracranial hemorrhage (SICH) percentages are for bleeding within the first 36 hours or the closest reported time point.
  • †
  • Indicates retrospective study; all others were prospective.

Results from meta-analysis of SICH in 15 published, open-label studies (N>2600) of Activase (t-PA)1,2:

The risks of Activase (t-PA) therapy to treat acute ischemic stroke may be increased in the following conditions:

  • Patients with severe neurologic deficit (eg, NIHSS score >22) at presentation; there is an increased risk of intracranial hemorrhage in these patients
  • Patients with major early infarct signs on a computerized cranial tomography (CT) scan (eg, substantial edema, mass effect, or midline shift)

The Cleveland Clinic Health System experience

Adapted from Katzan IL et al, Stroke. 2003;34:799.

  • ‡
  • One tertiary care center and 8 community hospitals.
  • §
  • Protocol deviations included: t-PA treatment given beyond 3 hours (n=7), antiplatelet agents or anticoagulant given within 24 hours (n=1), and deviations from blood pressure guidelines (n=3). t-PA administration was among all admitted ischemic stroke patients.


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After implementing a 2-year quality improvement program at 9 CCHS hospitals2:

  • Protocol violations were reduced by nearly half2
  • 6.4% incidence of SICH2

Indication
Activase (Alteplase) is indicated for the management of acute ischemic stroke in adults for improving neurological recovery and reducing the incidence of disability. Treatment should only be initiated within 3 hours after the onset of stroke symptoms, and after exclusion of intracranial hemorrhage by a cranial computerized tomography (CT) scan or other diagnostic imaging method sensitive for the presence of hemorrhage (see CONTRAINDICATIONS).

Important Safety Information
Activase therapy in patients with AIS is contraindicated in certain situations (eg, suspicion of subarachnoid hemorrhage on pretreatment evaluation, recent (within 3 months) intracranial or intraspinal surgery, history of intracranial hemorrhage, uncontrolled hypertension at time of treatment, active internal bleeding, known bleeding diathesis (eg, current use of oral anticoagulants, administration of heparin within 48 hours of onset of stroke, platelet count <100,000) (see CONTRAINDICATIONS for full list).

The most common complication during Activase therapy is bleeding. Should serious bleeding in a critical location (intracranial, gastrointestinal, retroperitoneal, pericardial) occur, Activase therapy should be discontinued immediately. Death and permanent disability are not uncommonly reported in patients who have experienced stroke (including intracranial bleeding) and other serious bleeding episodes.

The risks of Activase therapy may be increased and should be weighed against the anticipated benefits in certain conditions. [See WARNINGS in full prescribing information].

  • Patients with severe neurological deficit (eg, NIHSS >22) at presentation. There is an increased risk of intracranial hemorrhage in these patients.
  • Patients with major early infarct signs on a computerized cranial tomography (CT) scan (eg, substantial edema, mass effect, or midline shift).

Treatment of patients with minor neurological deficit or with rapidly improving symptoms is not recommended.

Orolingual angioedema has been observed in postmarketing experience in patients treated with Activase for AIS. Patients should be monitored during and for several hours after infusion for signs of orolingual angioedema.

Please click here for full prescribing information.
References:
1.
Graham GD. Tissue plasminogen activator for acute ischemic stroke in clinical practice: a meta-analysis of safety data. Stroke. 2003;34:2847-2850.
2.
Katzan IL, Hammer MD, Furlan AJ, et al. Quality improvement and tissue-type plasminogen activator for acute ischemic stroke: a Cleveland update. Stroke. 2003;34:799-800.
3.
Wahlgren N, Ahmed N, Dávalos A, et al; for the SITS-MOST Investigators. Thrombolysis with alteplase for acute ischaemic stroke in the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST): an observational study. Lancet. 2007;369:275-282.
4.
National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995;333:1581-1587.