10 May 2005 CASES - Original article available at CASES (Canadian Alteplase for Stroke Effectiveness Study) The CASES Investigators

10 May 2005 CASES - Original article available at 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

10 May 2005 CASES - Original article available at 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

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

10 May 2005 CASES - Original article available at 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

10 May 2005 CASES - Original article available at 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

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

10 May 2005 CASES - Original article available at 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

10 May 2005 CASES - Original article available at 90-day outcomes

10 May 2005 CASES - Original article available at 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%])

10 May 2005 CASES - Original article available at Frequency Onset-to-treatment time, min Time to treatment

10 May 2005 CASES - Original article available at 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

10 May 2005 CASES - Original article available at 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 )

10 May 2005 CASES - Original article available at ASPECTS predicts outcome Probability of excellent outcome Baseline ASPECTS score

10 May 2005 CASES - Original article available at 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

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