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

  2. 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). CASES - Original article available at www.cmaj.ca

  3. 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 CASES - Original article available at www.cmaj.ca

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

  5. 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 CASES - Original article available at www.cmaj.ca

  6. Baseline characteristics (n = 1135) Sex 55% male 45% female Handedness 95% right 4% left Symptom side 55% right 44% left 1% bilateral Mean age, yr 70 (SD 13, range 20–97) Ethnicity 91.3% white 4.5% Asian 4.8% other NIHSS score, median 14 (range 2–40) Note: NIHSS = National Institutes of Health Stroke Scale CASES - Original article available at www.cmaj.ca

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

  8. Baseline stroke risk factors CASES NINDS Hypertension 50% 67%* Ischemic heart disease 24% Prior TIA or stroke 23% 26.5% Atrial fibrillation 22% 18% Antiplatelet therapy 20% 33% High cholesterol 19% Diabetes mellitus 16% 20%* Current smoker 15% 31%* History of cancer 7% Congestive heart failure 7% 17.5%* Valvular heart disease 4% Subtherapeutic INR 3% Dementia 2% *p < 0.05 CASES - Original article available at www.cmaj.ca

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

  10. 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%]) CASES - Original article available at www.cmaj.ca

  11. Time to treatment 215 Frequency 0 0 60 120 180 240 300 360 Onset-to-treatment time, min CASES - Original article available at www.cmaj.ca

  12. 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 treatment 155 min Note: ED = emergency department CASES - Original article available at www.cmaj.ca

  13. Protocol violations and symptomatic ICH rate Protocol violations: – onset-to-treatment time > 180 minutes, platelet count < 100 ´ 109/L, INR > 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) CASES - Original article available at www.cmaj.ca

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

  15. Predictng symptomatic ICH Variable Odds ratio (95% CI) ­ baseline glucose 1.6 (1.2–2.3) per 5-mmol/Llevel increase in level ­ onset-to-treatment 1.2 (1.0–1.5) per 30-mintime increase in time CASES - Original article available at www.cmaj.ca

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