1. tPA… SMART or not SMART? That is the Question. Sarah Parker, MD

2. Disclosure – Sarah Parker I declare that I or my immediate family do not have a financial interest or other relationship with any manufacturer/s of a commercial product/s which may be discussed at the conference.

3. Epidemiology Newly announced that stroke has moved from the 4 th leading cause of death in the United States to the 5 th leading cause of death. Stroke is still the number one cause of adult disability in the United States

4. Percentage of patients with ischemic stroke who receive t-PA?

5. 4%

6. Activase therapy inpatients with acute ischemic stroke is contraindicated in the following situations because of an increased risk of bleeding, which could result in significant disability or death: Evidence of intracranial hemorrhage on pretreatment evaluation Suspicion of subarachnoid hemorrhage on pretreatment evaluation Recent (within 3 months) intracranial or intraspinal surgery, serious head trauma, or previous stroke History of intracranial hemorrhage Uncontrolled hypertension at time of treatment (e.g., >185 mmHg systolic or >110 mm Hg diastolic) Seizure at the onset of stroke Active internal bleeding Intracranial neoplasm, arteriovenous malformation, or aneurysm Known bleeding diathesis including but not limited to: – Current use of oral anticoagulants (e.g., warfarin sodium) or an International Normalized Ratio (INR) >1.7 or a prothrombin time (PT) >15 seconds – Administration of heparin within 48 hours preceeding the onset of stroke and have an elevated activated partial thromboplastin time (aPTT) at presentation – Platelet count <100,000/mm 3

7. In addition to the previously listed conditions, the risk of Activase therapy to treat acute ischemic stroke may be increased in the following conditions and should be weighed against the anticipated benefits: Patients with severe neurological deficit (e.g., NIHSS>22) at presentation. There is an increased risk of intracerebral hemorrhage in these patients. Patients with major early infarct signs on a computerized cranial tomography (CT) scan (e.g., substantial edema, mass effect, or midline shift). Due to the increased risk for misdiagnosis of acute ischemic stroke, special diligence is required in making the diagnosis in patients whose blood glucose values are 400 mg/dL. The safety and efficacy of treatment with Activase in patients with minor neurological deficit or with rapidly improving symptoms prior to the start of Activase administration has not been evaluated. Therefore, treatment of patients with minor neurological deficit or with rapidly improving symptoms is not recommended.

8. Contraindicated Evidence of intracranial hemorrhage Suspicion of subarachnoid hemorrhage Recent (within 3 months) intracranial or intraspinal surgery, serious head trauma, or previous stroke History of intracranial hemorrhage Uncontrolled hypertension at time of treatment (e.g., >185 mmHg systolic or >110 mm Hg diastolic) Seizure at the onset of stroke Active internal bleeding Intracranial neoplasm, arteriovenous malformation, or aneurysm Known bleeding diathesis INR >1.7 Administration of heparin within 48 hours and elevated aPTT Platelet count <100,000/mm 3 Minor neurologic deficit Rapidly improving symptoms Use caution NIHSS >22 Signs of ischemic stroke on CT Blood glucose 400

9. SMART (Simplifying Management of Acute Stroke using Revised Treatment) criteria Inclusion criteria – stroke symptoms starting within 4.5 hours of patient arrival. Exclusion criteria – symptomatic ICH on CT

10. tPA experience at OSF July 2010 – July 2014 218 patients 41% had a contraindication (n=90) Total of 154 contraindications

12. No significant difference ContraindicationsNo Contraindications Decrease in NIHSS44 MRS 0-243%42% Discharge Home or Rehab64.8%66.1% Symptomatic ICH1%2%

13. Outcomes

14. New Package Insert

17. Contraindicated Evidence of intracranial hemorrhage Suspicion of subarachnoid hemorrhage Recent (within 3 months) intracranial or intraspinal surgery, serious head trauma, or previous stroke History of intracranial hemorrhage Uncontrolled hypertension at time of treatment (e.g., >185 mmHg systolic or >110 mm Hg diastolic) Seizure at the onset of stroke Active internal bleeding Intracranial neoplasm, arteriovenous malformation, or aneurysm Known bleeding diathesis INR >1.7 Administration of heparin within 48 hours and elevated aPTT Platelet count <100,000/mm 3 Minor neurologic deficit Rapidly improving symptoms Use caution NIHSS >22 Signs of ischemic stroke on CT Blood glucose 400

18. Contraindicated Evidence of intracranial hemorrhage SAME Suspicion of subarachnoid hemorrhage CHANGE Recent (within 3 months) intracranial or intraspinal surgery, serious head trauma, or previous stroke CHANGE History of intracranial hemorrhage GONE Uncontrolled hypertension at time of treatment (e.g., >185 mmHg systolic or >110 mm Hg diastolic) CHANGE Seizure at the onset of stroke GONE Active internal bleeding SAME Intracranial neoplasm, arteriovenous malformation, or aneurysm CHANGE weigh risks/benifits Known bleeding diathesis SAME/CHANGE specific examples gone INR >1.7 GONE Administration of heparin within 48 hours and elevated aPTT GONE Platelet count <100,000/mm 3 GONE Minor neurologic deficit GONE Rapidly improving symptoms GONE Use caution NIHSS >22 GONE Signs of ischemic stroke on CT GONE Blood glucose 400 GONE NEW – When risk of bleeding is higher weigh the risks and benefits