30-Day Cardiac Event Monitor Belt for Recording Atrial Fibrillation After a Cerebral Ischemic Event (EMBRACE): A Randomized Controlled Trial

Project Leader:

David Gladstone, University of Toronto

Project Team:

Paul Dorian, University of Toronto
Melanie Spring, University of Toronto
Martin O’Donnell, McMaster University
Muhammad Mamdani, University of Toronto
Kevin Thorpe, University of Toronto
Andreas Laupacis, University of Toronto
Moira Kapral, University of Toronto
Richard Aviv, University of Toronto
John Blakely, University of Toronto
Robert Côté, McGill University
Mike Sharma, University of Ottawa
Ashfaq Shuaib, University of Alberta

Project Summary:

Atrial fibrillation (AF), the most common heart rhythm disorder in medical practice, is dangerous because it can lead to blood clots in the heart that can travel to the brain and cause stroke. Therefore, most patients who are recognized to have a stroke or “mini stroke” (TIA) caused by AF can benefit from the blood thinner warfarin to protect against recurrent strokes (warfarin reduces stroke risk by 67%). Without warfarin, the risk of recurrent strokes is high.

An unsolved problem is how to best diagnose AF because it is often intermittent and asymptomatic. Current methods for diagnosing AF are inefficient: most patients receive only a 24- or 48-hour heart rhythm recording (Holter monitor) and unless the AF occurs during the monitoring period, the diagnosis is missed, warfarin is not given, and a proportion of patients experience a recurrent stroke. An innovative new technology is now available to enable monitoring of patients for substantially longer periods. It is hypothesized that 30-day monitoring shortly after a stroke or TIA will be able to detect more patients with AF than a standard 24-hour monitor and prevent recurrent strokes.

EMBRACE is the largest study of its kind and the first randomized controlled trial to determine the optimal diagnostic strategy for detecting AF in stroke/TIA patients. Patients with a recent ischemic stroke/TIA of uncertain cause (“cryptogenic”), no known history of AF, and for whom the standard tests (ECG and Holter) have not revealed AF will be enrolled in the study. Half the patients will be randomly assigned to a 30-day electronic study monitor (experimental group) and half will be assigned to a repeat 24-hour Holter monitor (control group). The study monitor is programmed to automatically record episodes of AF. It is attached to a soft, lightweight elastic belt that is easily worn under clothing around the chest; it does not require electrodes that stick to the skin, so it is more comfortable than current monitors. The study will enroll 578 patients from 17 Canadian stroke centres over 2 years.

Promoting Adherence to Regimen of Risk Factor Modification by Trained Non-Medical Personnel (Volunteers) Evaluated against Regular Practice Study (PARTNERS):

Project Leader:

Richard Chan, University of Western Ontario.

Project Team:

Vladimir Hachinski, University of Western Ontario
Allan Donner, University of Western Ontario
Sumit Majumdar, University of Alberta
Finlay McAlister, University of Alberta
Robert Nolan, University of Toronto
Michael Harnadek, London Health Sciences Centre
Cheryl Mayer, London Health Sciences Centre
Leanne Casaubon, University of Toronto
Demetrius Sahlas, University of Toronto
Michel Beaudry, neurologist, Chicoutimee, QC
Brian Buck, neurologist Edmonton, AB
Barbara Hoppe, Memorial University of Newfoundland
David Howse, neurologist ,Thunder Bay Regional Hospital, ON
John Maher, neurologist, Barrie, ON
Arturo Tamayo, neurologist, Brandon Regional Hospital, MB

Project Summary:

PARTNERS is a project to identify the best strategy to reduce the impact of uncontrolled vascular risk factors in patients at high risk of developing ischemic strokes. Timely pharmacological interventions and the adoption of a healthy lifestyle can reduce the risk of stroke, but adherence to a regimen is crucial to success. Adherence is, in turn, dependent on the patients’ understanding of the effect of vascular risk factors, especially hypertension. The study will examine the efficacy, durability, and cost-effectiveness of a volunteer-facilitated risk modification program, compared against regular practice in patients who have experienced recent ischemic cerebrovascular events.

There will be 632 patients enrolled from 10 clinical centres in Canada. Patients are eligible for the study if they have experienced a recent ischemic cerebrovascular event and have hypertension. Participants will be randomized to receive regular practice (RP) or regular practice plus volunteer-facilitated risk modification program (RV). Patients in the RP group will receive usual medical care plus a 30-minute risk factor counseling by a nurse immediately following randomization. Patients in the RV group will receive standard medical management and 10 clinic or telephone contacts with the volunteer in the first year of follow-up. The volunteer will serve as an educator, a motivator, and a peer supporter. All patients will be followed by telephone contact or clinic visit every three months for two years. Primary outcome measure is the reduction in systolic BP from baseline to 12 months. Secondary outcome include measures of efficacy (magnitude of change in vascular or behavioral risk factor profile from baseline to 12 months), durability (magnitude of change in vascular or behavior risk factor profile from baseline to 24 months), clinical events (stroke, myocardial infarction, and/or death, cognitive decline), quality of life, and cost effectiveness of the intervention.

INTERSTROKE (Canada): Importance of Conventional and Emerging Risk Factors for Stroke in Different Regions of the World and in Different Ethnic Groups.

Project Leaders:

Martin O’Donnell, McMaster University
Salim Yusuf , McMaster University

Project Team:

Philip Teal, University of British Columbia
Moira Kapral, University of Toronto
Ashfaq Shuaib, University of Alberta
David Gladstone, University of Toronto
Gordon Gubitz, Dalhousie University
Frank Silver, University of Toronto
Mike Sharma, University of Ottawa

Project Summary:

Stroke is a major global public health problem. The overall purpose of INTERSTROKE is to learn about the role of known risk factors, such as high blood pressure, and emerging risk factors, such as genetics, for stroke in different regions of the world and ethnic groups. Members of the project team completed a similar study for myocardial infarction (MI). INTERHEART included 30,000 participants from 52 countries and showed that 9 modifiable risk factors accounted for over 90% of the risk. A similar study is necessary in stroke because:

• the causes of stroke are far more diverse than MI;
• many of the common risk factors for stroke and MI (e.g. lipids) appear to exert very different magnitudes of risk for stroke compared with MI, and;
• there are limited epidemiological studies in stroke.

This study compares risk factors in people with stroke (cases) to people without stroke (controls) in a large, international case-control study that includes approximately 30,000 cases and controls from about 32 countries. Countries will recruit the following ethnic groups: Caucasians, Chinese, South Asians, Africans and native South Americans. The pilot phase of INTERSTROKE, involving 8 countries, started in March 2007 and recruitment was to be completed in July 2008 (3,200 patients). The pilot phase, funded by the Canadian Institutes of Health Research, included 220 case-control pairs from Canada. Upon completion of the pilot phase of the study, there will be a transition into the full-scale study. For the full study, CSN funding enables recruitment of a further 880 pairs (total of 1,000 pairs) over 3 years from Canadian sites (6 sites).

INTERSTROKE will provide essential information on conventional and emerging risk factors that will guide population-based interventions to reduce the risk of stroke in Canada. INTERSTROKE will involve national and international collaboration. Central coordination of the study will be at McMaster University. The control group in INTERSTROKE-Canada will also serve as a cohort for completion of an imaging study to determine the prevalence and determinants of silent brain infarction. INTERSTROKE will have enormous implications for our understanding of the causes of stroke within Canada and around the world. It will also provide key information to help guide population health initiatives aimed at preventing stroke in low and high-income countries.

The Fast Assessment of Stroke and Transient Ischemic Attack to prevent Early Recurrence (FASTER) II Randomized Controlled Clinical Trial

Project Leaders:

Michael Hill, University of Calgary
James Kennedy, University of Oxford

Project Team:

Alastair Buchan, University of Oxford
Philip Teal, University of British Columbia
Ashfaq Shuaib, University of Alberta
Andrew Demchuck, University of Calgary
Daniel Selchen, Trillium Health Centre, Mississauga
Frank Silver, University of Toronto
Mike Sharma, University of Ottawa
Vladimir Hachinski, University of Western Ontario
Leo Berger, Hopital Charles LeMoyne, Montreal
Ariane Mackey, Quebec City, Quebec
Michel Beaudry, Chicoutimi, Quebec
Gordon Gubitz, Dalhousie University
Stephen Phillips, Dalhousie University

Project Summary :

The FASTER pilot trial was the first randomized clinical trial to address the question of how to prevent patients with a transient ischemic attack or minor stroke going on to have a further stroke. The international pilot phase was presented to some acclaim at the European Stroke Conference and the manuscript has been published in Lancet Neurology. It showed that rapid, early intervention may provide substantial benefit to patients, but the pilot phase was designed only as a proof-of-principle. This key piece of research was a Canadian Stroke Network funded project, which leveraged $500,000 CSN funding fourfold to a total of $2 million.

The FASTER II trial brings together the same core group of collaborators from across the Canadian Stroke Network. However, in order to deliver the sample size (~2500 patients) required for a main phase of a randomized clinical trial, it will require an international collaboration to ensure the timely completion of the trial. This will be realized through the strong links with the University of Oxford through to the UK Stroke Research Network. The expected output of this project would be evidence-based guidelines that would improve the chances of Canadians who experience a warning event to avoid a devastating stroke.