1. 10 May 2005 CASES - Original article available at www.cmaj.ca CASES (Canadian Alteplase for Stroke Effectiveness Study) The CASES Investigators

2. 10 May 2005 CASES - Original article available at www.cmaj.ca Conditions of use Please use these slides freely to describe the CASES study. For background information and details of the study, refer to the full report (published in the May 10, 2005, issue of CMAJ, available at www.cmaj.ca).

3. 10 May 2005 CASES - Original article available at www.cmaj.ca Financial disclosure CASES was funded by: –Hoffmann-La Roche Canada Ltd. –Canadian Stroke Consortium –Canadian Stroke Network Personnel were funded by: –Heart & Stroke Foundation of Canada –Canadian Institutes of Health Research

4. 10 May 2005 CASES - Original article available at www.cmaj.ca 60 centres actively treating stroke – 27 (45%) teaching hospitals – 33 (55%) community hospitals The majority of treating physicians were neurologists Centres

5. 10 May 2005 CASES - Original article available at www.cmaj.ca Patients CASES was a postmarketing registry of patients with acute ischemic stroke receiving treatment with the tissue plasminogen activator (tPA) alteplase A total of 1135 patients were enrolled – 25 patients were lost to all follow-up after 24 hours

6. 10 May 2005 CASES - Original article available at www.cmaj.ca Baseline characteristics (n = 1135) Sex55% male45% female Handedness95% right4% left Symptom side55% right44% left1% bilateral Mean age, yr70 (SD 13, range 20–97) Ethnicity91.3% white4.5% Asian4.8% other NIHSS score, median14 (range 2–40) Note: NIHSS = National Institutes of Health Stroke Scale

7. 10 May 2005 CASES - Original article available at www.cmaj.ca Baseline volume High volume (> 1 patient/month): –10 centres (61% of patients) Low volume (< 1 patient/month): –50 centres (39% of patients)

8. 10 May 2005 CASES - Original article available at www.cmaj.ca Baseline stroke risk factors CASESNINDS Hypertension50%67%* Ischemic heart disease24% Prior TIA or stroke23%26.5% Atrial fibrillation22%18% Antiplatelet therapy20%33% High cholesterol19% Diabetes mellitus16%20%* Current smoker15%31%* History of cancer7% Congestive heart failure7%17.5%* Valvular heart disease4% Subtherapeutic INR3% Dementia2%*p < 0.05

9. 10 May 2005 CASES - Original article available at www.cmaj.ca 90-day outcomes

10. 10 May 2005 CASES - Original article available at www.cmaj.ca Adverse events Symptomatic intracranial hemorrhage (ICH): –52 patients (4.6% [95% CI 3.4%–6.0%]) –90-day mortality: 79% Anaphylactoid/angioedema reaction –15 patients (1.3% [95% CI 0.7%–2.2%])

11. 10 May 2005 CASES - Original article available at www.cmaj.ca Frequency Onset-to-treatment time, min 060120180240300360 0 215 Time to treatment

12. 10 May 2005 CASES - Original article available at www.cmaj.ca Median interval times Onset to ED 56 min ED to CT scan 36 min CT scan to treatment 44 min Door to treatment 85 min Onset to treatment155 min Note: ED = emergency department

13. 10 May 2005 CASES - Original article available at www.cmaj.ca Protocol violations and symptomatic ICH rate Protocol violations: – onset-to-treatment time > 180 minutes, platelet count 1.4, tPA dose > 90 mg Symptomatic ICH rate: – 7.8% (violation) v. 3.9% (no violation) RR 2.0 ( 95% CI 1.1–3.8 )

14. 10 May 2005 CASES - Original article available at www.cmaj.ca ASPECTS predicts outcome Probability of excellent outcome Baseline ASPECTS score

15. 10 May 2005 CASES - Original article available at www.cmaj.ca Predictng symptomatic ICH VariableOdds ratio (95% CI)  baseline glucose 1.6 (1.2–2.3) per 5-mmol/L levelincrease in level  onset-to-treatment1.2 (1.0–1.5) per 30-min timeincrease in time

16. 10 May 2005 CASES - Original article available at www.cmaj.ca Conclusions — goals met! Alteplase is safe and effective for the “real-world” clinical treatment of acute ischemic stroke.