Recruitment Profile
	Baseline Characteristics of Patients
	Baseline ASPECTS (Alberta Stroke Program Early CT Score)
	Patients Outcomes at 90-day Follow-up
	Observed vs Expected Outcomes Among CASES Patients
	Adverse Events in CASES Patients

Background

Thrombolysis for acute ischaemic stroke has remained controversial. The Canadian Alteplase for Stroke Effectiveness Study, a national prospective cohort study, was conducted to assess the effectiveness of alteplase therapy for ischaemic stroke in actual practice.

Methods

A total of 76 centres have been registered. Of these, 60 are actively submitting data to the study. There are 25 tertiary care sites and 35 community sites. Centres from nine of the 10 provinces in Canada are represented. A total of 944 patients have been entered. cruitment progress until 27 March 2001 is shown in the figure.

Reference:
Hill MD, Buchan AM. Can J Neurol Sci 2001; 28: 232-238.

Recruitment Profile

Reference:
Hill MD, Buchan AM. Can J Neurol Sci 2001; 28: 232-238.

The study was mandated by the federal government as a condition of licensure of alteplase for the treatment of stroke in Canada. A registry was established to collect data over 2.5 years for stroke patients receiving such treatment from February 17, 1999, through June 30, 2001. All centres capable of administering thrombolysis therapy according to Canadian guidelines were eligible to submit patient data to the registry. Data collection was prospective, and follow-up was completed at 90 days after stroke. Copies of head CT scans obtained at baseline and at 24-48 hours after the start of treatment were submitted to a central panel for review.

Reference:
Hill MD, Buchan AM. Can J Neurol Sci 2001; 28: 232-238.

Baseline Characteristics of Patients

Characteristic	% of patients n = 1135
Demographic
Age > 70 yr Male sex White	59.0 54.9 83.2
Medical history
Previous stroke or TIA Hypertension Atrial fibrillation Diabetes mellitus Hypercholesterolemia Ischaemic heart disease Congestive heart failure Valvular heart disease Dementia History of cancer	23.6 50.7 22.2 15.9 19.0 24.9 6.9 3.7 2.1 7.4
Clinical measure
PNIHSS score > 15 ASPECTS score > 7 Serum glucose level > 8mmol/L Mean arterial pressure on admission > 100 mm HG Type of stroke*    Posterior circulation    Total anterior circulation    Partial anterior circulation    Lacunar	44.0 56.8 27.0 61.1 3.5 27.5 63.0 6.0
Process measure
Time from stroke onset to treatment < 120 min Protocol violation High-volume centre#	20.8 13.6 61.6

Note: NIHSS = National Institutes of Health Stroke Scale, ASPECTS = Alberta Stroke Programm Early CT Score.
* As determined using the Oxfordshire Community Stroke Projekt (OCSP) classification.
# Treated one or more patients per month

Reference:
Hill MD, Buchan AM. Can J Neurol Sci 2001; 28: 232-238.

Results:
The Baseline ASPECTS (Alberta Stroke Program Early CT Score) as predictor of an excellent outcome (functional independence) in patients experiencing an acute ischaemic stroke is shown in the figure. A higher baseline score is associated with a greater probability of an excellent outcome. Data are based on a fitted logistic regression model that adjusted for baseline NIHSS (National Institutes of Health Stroke Scale) score, age and baseline serum glucose level. The curve was generated from point-wise confidence intervals (CIs); the screened area represent 95% CIs.

Hill MD, Buchan AM. Can J Neurol Sci 2001; 28: 232-238.

Baseline ASPECTS (Alberta Stroke Program Early CT Score)

A total of 1135 patients were enrolled at 60 centres in all major hospitals across Canada. The registry collected data for an estimated 84% of all treated ischaemic stroke patients in the country.

The registry collected data for an estimated 84% of all treated ischaemic stroke patients in the country.

Residence refers to where the patient was living at the 90-day followup. Adjusted mRS implies difference between mRS score at 90-day follow-up and mRS score before stroke. This adjustment provides a composite measure of patients who achieved either an excellent functional outcome or returned to their baseline level of function, or both. For example, a patient with a baseline mRS score of 3 who had a score of 3 at 90 days Would be rated in the �excellent outcome� category.

An excellent clinical outcome was observed in 37% of the patients.

Reference:
Hill MD, Buchan AM. Can J Neurol Sci 2001; 28: 232-238.

Patients Outcomes at 90-day Follow-up

Reference:
Hill et al. CMAJ 2005; 172 (10): 1307-1312.

Observed vs. Expected Outcomes Among CASES Patients

Reference:
Hill et al. CMAJ 2005; 172 (10): 1307-1312.

Adverse Events:
Symptomatic intracranial haemorrhage occurred in only 4.6% of the patients (95% confidence interval [CI] 3.4% 6.0%); however, 75% of these patients died in hospital. An additional 1.3% (95% CI 0.7%-2.2%) of patients had haemiorolingual angioedema.

Adverse Events in CASES Patients

Adverse event	No. of patients	% of patients(95% CI)
Symptomatic intracranial haemorrhage	52	4.6 (3.4-6.0)
Major systemic bleeding	4	0.4 (0.1-0.9)
Orolingual angioedema	15	1.3 (0.7-2.2)
Acute hypotension	4	0.4 (0.1-0.9)
All	75	6.6 (5.2-8.2)

Note: CI = confidence interval.

Conclusions
The outcomes of stroke patients undergoing thrombolysis in Canada are commensurate with the results of clinical trials. The rate of symptomatic intracranial haemorrhage was low. Stroke thrombolysis is a safe and effective therapy in actual practice.

Reference:
Hill MD, Buchan AM. Can J Neurol Sci 2001; 28: 232-238.