CVC Annual Report 2010 by Canadian VIGOUR Centre

Annual Report 2010

“The ﬁnal test of a leader is that he leaves behind him in others the conviction and the will to carry on.” —Walter Lippman

Table of Contents Message from the Director

CVC at a Glance

Background

Our Mission

CVC Core Values

Faculty Leaders

Key Personnel

Collaborations

External Advisors

Spectrum and Evolution: A Snapshot of CVC's Clinical Trial Experience

CVC Services

å Clinical Investigation, Project Management & Monitoring

å ECG Core Laboratory

å Activities of the ECG Core Laboratory å Academic Research Projects from Clinical Trials and Population Laboratory

35 36

å Research Training & Continuing Medical Education

Sources of Clinical Trial Revenue

Awards, Honours and Grants

Future Research

Publications—2010

Appendix 1: The Canadian Cardiac Chronicle Newsletters

Appendix 2: Beyond 2000 Program

Acknowledgements

Message from the Director I am pleased to introduce the 2010 Annual Report of the Canadian VIGOUR Centre (CVC), an academic research organization (ARO) which functions as an official research centre within the University of Alberta, Faculty of Medicine and Dentistry.

Our excellent faculty consisting of Justin Ezekowitz, Padma

Our senior operational leadership team consisting of

Kaul, Finlay McAlister and Rob Welsh have made great

Tracy Temple, Cindy Westerhout and Dianne Payeur has

strides in helping us to embrace the critical quality cycle

made quality a key focus across the full spectrum of our

that intersects early scientiﬁc development, the various

activity including clinical operations, the ECG Core Lab, data

evolutionary phases of clinical trials, the incorporation into

management and biostatistics. Our project team is ably

clinical practice guidelines, whether or not these guidelines

supported by a terriﬁc administrative staff. Our Core ECG

affect performance and how performance may ultimately

Laboratory staff has made great strides in the past year

impact on the health of populations such as our fellow

and along with our biostatistics group serve as welcome

Albertans. It is appropriate to acknowledge that all of the

resources for the research trainees we are privileged to

clinical investigators on CVC faculty have played key roles

mentor as they develop their professional careers. In

in guideline development and advancing the incorporation

addition, we at CVC are grateful for the tremendous support

of new science into recommendations for diagnosis and

we have received from our valued investigative network

management. I am pleased that my colleague, Padma Kaul,

across the ten provinces of Canada.

has accepted the leadership role as Director, Outcomes Research in CVC since her key leadership in this arena enhances closure of the quality cycle as noted above.

Annual Report — Two-thousand and Ten — Canadian VIGOUR Centre

Message from the Director

Our faculty and leadership team play a key role in research

for a cardiologist) comprehend the intricacies of oral

mentoring of medical students; trainees in Internal Medicine

hypoglycemics.

and Cardiology; and foreign medical graduates as they seek to sharpen their analytical skills and gain invaluable lessons from the discipline of research and its commensurate satisfaction. Some of CVC’s 2010 highlights: å In collaboration with our partners at DCRI and internationally, we completed the largest ever study of patients with acute heart failure (ASCEND HF). While the conclusion may be disappointing to some, it is nonetheless rewarding to put to rest prior concerns about the safety of nesiritide infusion in acute heart failure. The lack of efficacy of this agent on mortality and re-hospitalization for acute heart failure highlight an enormous opportunity and unmet need amongst patients with this previously neglected, common and increasingly important manifestation of acute cardiovascular disease. The as yet largely untapped rich data derived from the ASCEND-HF data base will most assuredly point us in useful future directions. In particular the leadership of Justin Ezekowitz in developing a key respiratory substudy that provides a newly validated tool in the form of peak expiratory flow rate (derived from bedside spirometry) to aid in the assessment of dyspnea will be very useful in our future research. å Our core ECG team finished analyzing over 15,000 patient ECGs from the PLATO study (Study of PLATelet Inhibition and Patient Outcomes) in December. This unique dataset will provide new insights into the role of ticagrelor a novel

The 2010 year was important for the international VIGOUR group, it marked the 20th anniversary of the ﬁrst GUSTO clinical trial and included a variety of efforts to attempt to enhance global collaboration in cardiovascular medicine. The VIGOUR group journeyed to São Paulo Brazil in October to welcome its newest member organization Brazilian Clinical Research Institute (BCRI) headed by Dr. Renato Lopes. Under his leadership, an international symposium “III International Symposium of Thrombosis and Anticoagulation (ISTA)”was held in October of 2010 and proved to be a stimulating opportunity to share insights into the best contemporary approach to atherothrombosis. As well, we achieved enhancement of VIGOUR’s global worldwide mission and collaboration. In a piece published in the European Heart Journal authored by Dr. Robert Califf in collaboration with members of the VIGOUR group, a new order in cardiovascular medicine is contemplated through a re-engineering of global collaboration. (EHJ 2010; 31:911-917). The VIGOUR Leaders had robust and substantial discussions relating to our collaborative future in global cardiovascular research. We recognize the importance of emerging new academic research organizations and the next generation of VIGOUR leaders as noted above. With kind regards,

platelet antagonist that will shortly be introduced into clinical practice. å CVC has been actively engaged in collaborative efforts aimed at improving cardiovascular outcomes amongst patients with type 2 diabetes. This initiative is bringing

together diabetologists and cardiologists in a true interdisciplinary effort that has worldwide public health implications. Oral hypoglycemics have attracted enormous interest recently especially given their impact (or lack thereof) on cardiovascular outcomes. Indeed the FDA’s new mandate to evaluate the public health implications on cardiovascular outcomes of hypoglycemic agents has deﬁnitely generated new opportunities for clinical research. Whether hypoglycemic agents that affect insulin release, the process of glucose absorption, the modulation of insulin-like hormones released from the gut or the effects of glucose uptake in muscle or fat cells are optimal is unclear. It’s astonishing to appreciate that diabetes affects over 250 million people worldwide and, like obesity, is rapidly becoming a global epidemic. It is one thing to manage a complex pharmacological proﬁle of six or seven drugs in a patient convalescing from an acute myocardial infarction and quite another to (at least

Canadian VIGOUR Centre — Two-thousand and Ten — Annual Report

Paul W. Armstrong, MD D

CVC at a glance Number of patients enrolled globally in studies

Number of Canadian patients enrolled in CVC studies

in which CVC has participated

260,000

17,000

Primary Investigator Participation in

Proﬁle of Site Investigators

CVC Administered Clinical Trials

by Area of Specialization 6% Others* 1% Hematology 54% Participating in 1 trial

26% Cardiology 19% Internal Medicine

n=440

n=440 5% Endocrinology 1% Cardio Interventionalist

46% Participating in more than 1 trial

4% Echocardiology 38% Cardio/ Internal Medicine *Nephrology, family, anaesthesiology, pulmonary, gastroenterology

Employees by Core Activities (2010)

Faculty Mentoring & Research Trainee Supervision by Dr. Armstrong 1997-2010

10% Admin/Finance/Business

19% Faculty Mentored

28% Clinical Operations 15% ECG Core Lab

n=40

n=64

13% Health Outcomes

8% Biostatistics

28% Monitors

81% Research Trainees Supervised

Annual Report — Two-thousand and Ten — Canadian VIGOUR Centre

Background, Our Mission, CVC Core Values

Background

Our Mission

The Canadian VIGOUR Centre (CVC) was established in 1997

Aligned with the University of Alberta, the mission of

as the Canadian arm of the international VIGOUR Group.

CVC is the generation, translation & dissemination of

The VIGOUR Group is an academic research organization

knowledge on novel, diagnostic and therapeutic strategies

composed of thought leaders in cardiovascular medicine

in cardiovascular medicine acquired through collaboration in

and clinical investigation who have achieved international

cardiovascular research to enhance the health of the citizens

recognition and since its inception CVC has undertaken over

of Alberta, Canada, and the world.

43 clinical trials in cardiovascular disease. Its operations extend from phase II and III clinical trials through regional registries and population health outcomes. It garners support through research grants and contracts from industry and external peer-reviewed agencies as well as the University of Alberta’s Mazankowski Alberta Heart Institute and Alberta Health Services. The Centre employs 20 full-time staff located primarily on the University campus and contracts a monitoring team of eight Clinical Research Associates (CRA) located across the country.

CVC Core Values Quality

Collaboration

Integrity

Aspire to the highest standard of work while respecting a balanced life perspective. Attract, mentor and retain high quality colleagues and collaborators with similar core values.

Promote and support an outstanding team that integrates a diversity of knowledge, experience, ideas, and skills supportive of our mission/vision.

Perform our roles in an ethical framework which enhances our reputation as honest, trustworthy and responsible.

Create an innovative, engaging and inclusive work environment, appreciative of

Respect

individual differences and contributions. Our workplace will be conductive to personal growth and development that is aligned with our overall mission.

Emerging from CVC Advance January 2009

Canadian VIGOUR Centre — Two-thousand and Ten — Annual Report

Faculty Leaders

Faculty leaders Paul W. Armstrong, MD Director, CVC Paul W. Armstrong, MD is Distinguished University Professor, Department of Medicine Division of Cardiology at the University of Alberta, Edmonton, Alberta, Canada and Director of the Canadian VIGOUR Centre. Dr. Armstrong’s principal investigative focus, involves the pathophysiology, diagnosis and management of acute coronary syndromes and congestive heart failure. Having been principally involved in the introduction of novel ﬁbrinolytic therapy to Canada over 20 years ago, he and his colleagues have spearheaded a comprehensive and transforming initiative to further enhance the care of patients with ST-elevation myocardial infarction given that you need time sensitivity on the one hand, and the failure of patients so afﬂicted to arrive at health care institutions in a timely manner on the other so as to receive life-saving therapy. This concept is now being actively translated into other common and time sensitive life-threatening conditions namely acute non ST-elevation myocardial infarction and congestive heart failure. Dr. Armstrong has had a lifelong commitment to the education and training of healthcare professionals. A number of his many former trainees, residents and research fellows have won research prizes and awards under his tutelage and have gone on to academic positions in Canada and internationally. His mentorship of trainees and faculty has been a key signature of his career and is recognized both nationally and internationally.

Annual Report — Two-thousand and Ten — Canadian VIGOUR Centre

Faculty Leaders

Padma Kaul, PhD Director, Outcomes Research, CVC Associate Professor, University of Alberta Adjunct Assistant Research Professor, Duke University Medical Center In September 2010, CVC was pleased to recognize Dr. Kaul’s key leadership in population outcomes by appointing her the Director of Outcomes Research in CVC Dr. Padma Kaul is an Associate Professor in the Department of Medicine at the University of Alberta, Edmonton, Alberta, Canada and an Adjunct Assistant Research Professor at Duke University Medical Center, Durham, North Carolina and an Adjunct Professor at the School of Public Health at the University of Alberta, Edmonton, Alberta, Canada. Dr. Kaul is an Alberta Innovates – Health Solutions (previously Alberta Heritage Foundation for Medical Research) Population Health Investigator. She is an epidemiologist and policy analyst by training and commits 75% of her time to research. Her research interests can be broadly classiﬁed into four areas: 1) international

patients with heart failure.

differences in practice patterns and outcomes; 2) sex differences in treatment and outcomes of cardiovascular

In the current environment of constrained health care

disease; 3) issues related to access and delivery of care at a

resources, in Canada and the rest of the world, a new health

population level; and 4) health economics.

technology must demonstrate not only that it is clinically

beneﬁcial, but also that it is cost-effective. Facilitated by

Dr. Kaul is currently the Principal Investigator (PI) of a CIHR

the adjunct appointment at Duke University, Dr. Kaul has

funded grant examining sex differences in presentation,

been the co-PI on the economic substudies of several

treatment and outcomes of patients with acute coronary

international trials. She is currently a Co-PI of the economic

syndromes. The burden of cardiovascular disease, the

substudy of TRILOGY; and the Canadian lead on the

leading cause of morbidity and mortality in Canada, is being

economic substudy of PLATO and the ASCEND-HF trials.

increasingly borne by women. As part of the project, she is examining why women with heart attacks delay seeking medical attention and what are the consequences of this delay. Dr. Kaul has over ten years of experience working with large health care administrative databases, maintained by the provincial government (Alberta Health and Wellness), which are key to examining these issues at a populationlevel. Her team has developed an integrated database linking data from several sources (inpatient, outpatient, emergency department, physician ofﬁces, census, and vital status) , which has been used to examine a wide array of clinical and policy-relevant questions including: 1) the long-term outcomes of patients presenting with acute coronary syndromes and heart failure; 2) the effect of socioeconomic status on access to and outcomes of coronary revascularization procedures; 3) the impact of specialist care on outcomes; and 4) the costs of end of life care among

Canadian VIGOUR Centre — Two-thousand and Ten — Annual Report

Faculty Leaders

has led the development of a heart failure registry and has access to data from a number of databases, the support of statisticians and epidemiologists, and a proven methodology. These resources allow him to study differences in outcomes in former and current patients where he can learn a great deal about the impact of drugs and processes of care. Of significant interest to Dr. Ezekowitz is practical clinical trial design for heart failure, and he is also interested in trials and research associated with end of life issues or comorbidities such as atrial fibrillation and hip fractures. Dr. Ezekowitz has published numerous papers related to heart failure. His research on anemia in heart failure has highlighted how important anemia is in disease (Circulation. 2003;107(2):223-225) and he is hopeful that current large clinical trials involving anemia in these patients will provide insights on better methods to manage these patients. In addition, he has been involved in a large systematic review on devices, defibrillators and pacemakers in heart failure which has identified large knowledge gaps which are currently the focus of clinical trials. Currently, Dr. Ezekowitz is the Principal Investigator of two significant heart failure trials and serves on the Steering

Justin Ezekowitz, MD

Committee for two major international trials, namely the

Assistant Professor, Division of Cardiology, University of Alberta Director, Heart Function Clinic

ﬁbrillation) and the Acute Studies of Clinical Effectiveness

ARISTOTLE trial (a 15,000 patient trial of high risk atrial of Nesiritide in Decompensated Heart Failure (ASCEND-HF, a 7,000 patient global trial). Additionally, he has designed and received funding for three substudies derived from the ASCEND –HF trial.

Dr. Ezekowitz, a practicing Cardiologist, Director of a Heart Function Clinic and CIHR, AHFMR Population Health

Dr. Ezekowitz is a Member Canadian Cardiovascular Society

Investigator, has been collaborating with the CVC since

Heart Failure Guidelines and is involved with several

2001. Passionate about trying to improve the outcomes of

organizations including the Heart and Stroke Foundation,

his patients with congestive heart failure, he dedicates about

CIHR, the American Heart Association, College of Cardiology

75% of his time to clinical research to better understand

and Heart Failure Society of America, plus he collaborates

this disease and to increase the amount of clinical evidence

with many individuals in Canada, the US and Europe.

available to improve the process and quality of care for these patients. According to Dr. Ezekowitz, “this disease is a big burden on Canada’s healthcare system. It is responsible for 1.4 million hospital days/year which costs between 3-4 billion dollars in Canada alone. If someone gets admitted to hospital with heart failure, they are likely to be re-admitted.” The need for research to address the system demand is compelling, and Dr. Ezekowitz’ goal is to ﬁgure out how to keep people healthy and out of the hospital, and if they are admitted to the hospital, to ﬁgure out how we can reduce the 10% death rate in-hospital and the 30% death rate within one year. Dr. Ezekowitz is also a population health researcher and holds peer reviewed grants from CIHR and AHFMR. He

Annual Report — Two-thousand and Ten — Canadian VIGOUR Centre

Faculty Leaders

Finlay A. McAlister MD Professor of Medicine, University of Alberta Director, Patient Health Outcomes Research Institute, University of Alberta President, Canadian Society of Internal Medicine 2009-2011 Dr. Finlay McAlister is a Professor of Medicine, Division of General Internal Medicine at the University of Alberta and is a practicing general internist. He has published more than 250 research papers in peer reviewed journals, many of which are esteemed, on a variety of topics including outcomes research in hypertension, heart failure, perioperative care, and coronary artery disease, as well as clinical epidemiology methodology with a focus on guideline development and implementation schemes, trial methodology, and systematic reviews. He is currently the President of the Canadian Society of Internal Medicine; Director, Patient Health Outcomes Research Institute at the University of Alberta; Assistant Director of the Epidemiology Coordinating and Research Centre at the University of Alberta; Chair, Outcomes Research Task Force for the Canadian Hypertension Education Program; and is active in many other organizations including the Canadian Cochrane Network and various editorial boards. Dr. McAlister has collaborated with CVC Faculty and research staff for many years and enjoys collaborating with people in a wide range of areas in clinical research. He is interested in trying to improve the implementation of evidence at

"Quality research should answer the question deﬁnitively or appropriately highlight the limitations of the evidence, in order to stand the test of time."

the bedside and the interpretation of evidence at bedside for many cardiovascular conditions including hypertension and heart failure. In his new role as Director of the Patient

—Finlay A. McAlister, MD

Health Outcomes Research Institute, he plans to bring together various health outcomes researchers to create a

Dr. McAlister is committed to quality research and he would

common foundation for accessing administrative data from

like his research to “answer the question deﬁnitively or

Alberta Health and Wellness and Alberta Health Services

appropriately highlight the limitations of the evidence, in

as well as to bring together various patient registries to

order to stand the test of time".

facilitate more comprehensive health outcomes research. Dr. McAlister is a Fellow of the Canadian Academy of Health Some of Dr. McAlister’s signiﬁcant contributions to research

Sciences and has won numerous awards including the

include:

Merck Frosst/ Aventis Chair in Patient Health Management,

å Systematic reviews

the Young Investigator Award of the Canadian Society of

å Identifying discrepancies between clinical practice and

Internal Medicine, and the Royal College Medal in Medicine

the evidence base å Strategies to enhance evidence uptake to optimize patient care å Perioperative risk stratiﬁcation.

Canadian VIGOUR Centre — Two-thousand and Ten — Annual Report

from the Royal College of Physicians and Surgeons in Canada. He currently holds a Senior Health Scholar Award from the Alberta Heritage Foundation for Medical Research/ Alberta Innovates-Health Solutions.

Faculty Leaders

intervention versus lysis drug. Time is undoubtedly the single most important thing that we can change. Because the risk of the disease is there regardless of what we do, … the best thing that a medical system can do to improve the outcomes is to decrease the time between the cardiac event and the time to receive deﬁnitive medical care.” Welsh’s team undertook to personally train the paramedics and those ﬁrst attending heart attack victims in the greater Edmonton region, to put his pursuit of more timely care into action. “By using the ambulance and the skills from the ambulance personnel, we are now taking anywhere from 45 minutes to an hour and a half off time to treatment depending on where patients present.” The heart attack treatment programs cover the majority of central and northern Alberta, and takes advantage of the most current technological capabilities of the rural health facilities, which normally would not have such immediate access to cardiac expertise in their region. Steadfast in his commitment to improve patient care and their outcomes, Rob and his team have established processes which provide timely feedback to the caregivers

Robert Welsh, MD

participating in these programs, so that all participants can

Associate Professor, Division of Cardiology, University of Alberta Interventional Cardiologist, Mazankowski Alberta Heart Institute Director, Adult Cardiac Catheterization and Interventional Cardiology program Co-Director, University of Alberta Chest Pain Program

safe and effective, and that result, ultimately, in improved

Robert Welsh is an associate professor and academic interventional cardiologist at the Mazankowski Alberta Heart Institute and University of Alberta in Edmonton, Alberta, Canada. He is the director of Adult Cardiac Catheterization and Interventional Cardiology program. He is also the codirector of the University of Alberta Chest Pain Program, which he initiated and designed in collaboration with Dr. Brian Holroyd (Chief, Emergency Medicine). He is co-chair of Vital Heart Response, a regional reperfusion program for early treatment of STEMI patients. He is co-chair of the Mazankowski Alberta Heart Institute Transcatheter Aortic Valve Intervention program (TAVI).

work to formalize changes to their processes of care that are care and outcomes for heart attack patients. To assist with this clinical research, Dr. Welsh implemented a Vital Heart Response registry which has tracked heart attack patients in the greater Edmonton region since 2007. Since his ﬁrst collaboration with CVC in 1999, Rob has played an active role with the CVC in the design and championing of various cardiovascular clinical trials. These include the investigation of novel antiplatelet therapies in acute coronary syndromes, pre-hospital management of STEMI and the interaction of pharmacological (antithrombotic and ﬁbrinolytic) and mechanical interventions (primary and rescue angioplasty) which are a major focus of his clinical research. Dr. Welsh continues to be actively involved in research with patients with acute coronary syndromes. Recently he expanded his clinical research interests to understand the implications of and interplay between cardiovascular disease and diabetes and to explore exercise physiology and cardiac physiology. Rob is also involved in Postgraduate training (Masters and PhD).

While still a trainee, Rob recognized both the need and the opportunity to improve the care of heart attack patients by beginning treatment earlier, in fact, before they arrive at the hospital. According to Dr. Welsh, for patients having a heart attack, “if you want to change outcomes, time to treatment has a bigger impact than percutaneous coronary

Annual Report — Two-thousand and Ten — Canadian VIGOUR Centre

Key Personnel

Dianne Payeur, MBA

Yuling Fu, MD

Assistant Director

Consultant, ECG CORE Laboratory

Dianne Payeur has a pivotal role in the leadership of CVC,

Yuling Fu, MD is an Assistant Clinical Professor in the

and in her position of Assistant Director, she is responsible

Department of Medicine at the University of Alberta,

for ﬁnancial and human resource management, strategic

Director of CVC’s ECG CORE Laboratory. Dr. Fu’s main area

planning including marketing and IT infrastructure, and

of research involves studying the prognostic utility of the

contractual negotiations for CVC’s clinical operations. Dianne

electrocardiogram in the risk stratiﬁcation of patients with

has extensive experience in business development, strategic

acute coronary syndromes and identifying research areas in

planning and ﬁnancial management, and has made a

which the ECG Core Laboratory provides added value to the

signiﬁcant contribution to CVC in terms of quality assurance

overall investigative process of clinical trials. She provides

and process improvements, and has led CVC’s operations in

consultation to our team of ECG interpreters in high quality

making substantive and measurable impacts on many key

analysis of ECG data arising from clinical trials of acute

performance indicators within our service offerings, which

cardiovascular disease. She continues to provide research

highlight the value and contribution CVC can and has made

mentorship and guidance to University of Alberta trainees

in our involvement with clinical trials. She has a Masters of

and students.

Business Administration degree and her strong personal leadership skills are an asset to our organization.

Canadian VIGOUR Centre — Two-thousand and Ten — Annual Report

Key Personnel

Hany Siha, MBBCh

Tracy Temple

Assistant Director, ECG CORE Laboratory.

Manager, Clinical Operations

Dr. Hany Siha has been a senior member in the CVC’s ECG

Tracy Temple started with our organization in April 2000

CORE Laboratory group and in 2010 became Assistant

as a Project Manager. She is a Registered Nurse with a

Director of this lab. He has been involved in research on

Bachelor of Science in Nursing and experience in CCU,

the prognostic utility of the ECG in the risk stratiﬁcation of

Cardiothoracic Surgery and CVICU. She has her SOCRA

patients with acute coronary syndromes based on the data

CCRP (Certiﬁed Clinical Research Professional) designation.

generated by this group. Dr. Siha is responsible for training

Having worked as a Project Manager on several trials

of new ECG personnel and for maintaining the consistency

since April 2000, in October 2008 Tracy took on the

of processes, methodologies and standard operating

role as Manager of Clinical Operations and now oversees

procedures in efforts to ensure data integrity.

the day to day functions of our Clinical Operations and Monitoring teams. In this role she is an ambassador for the organization, works to establish and implement standard operating procedures, is a resource and mentor, is responsible for implementing ongoing training initiatives for the clinical operations group and ensures quality control measures are in place. Quality control and assurance initiatives have been a strong focus for her and her team over this last year and will continue to be through 2011.

Annual Report — Two-thousand and Ten — Canadian VIGOUR Centre

Key Personnel

Cynthia Westerhout, PhD

Halina Nawrocki

Assistant Director, Biostatistics

Lead Clinical Research Associate

Cynthia (Cindy) Westerhout, PhD is a Senior Research

Halina Nawrocki transitioned into the Lead Clinical Research

Associate and Assistant Director of the CVC. She completed

Associate position in 2010 and has worked as a Clinical

her doctoral studies in Clinical Epidemiology (Cardiology)

Research Associate (CRA) with CVC for over seven years.

at Erasmus University (Rotterdam, the Netherlands) in

Based in Mississauga, Ontario, Halina currently monitors

2007. Her research interests include novel risk stratiﬁcation

sites across Canada. She has extensive experience as a

techniques and risk adjustment procedures in acute

cardiology nurse, study coordinator, and clinical trials

coronary syndromes and acute heart failure. Active research

monitor. Prior to working with CVC, Halina worked as a

collaborations include the Duke Clinical Research Institute

Clinical Research Associate (CRA) in the pharmaceutical

(Durham, NC) and Erasmus Medical Center (Rotterdam, The

industry. Halina has a particular interest in the regulatory

Netherlands).

affairs aspect of clinical trials.

In addition to research activities, she provides statistical oversight and consultation to the CVC Research Group, medical residents and students and arranges statistical training programs for the same. She is also responsible for standard operating procedures, quality control and assurance for biostatistics group. She serves as the biostatistics representative to the CVC Faculty and CVC Leadership Team and to Global VIGOUR Group and other external groups (e.g., trial statistical working groups).

Canadian VIGOUR Centre — Two-thousand and Ten — Annual Report

Collaborations, External Advisors

Collaborations

External Advisors

The CVC is afﬁliated with VIGOUR, a global collaboration of

å Robert M. Califf, MD, Vice Chancellor for Clinical Research,

coordinating centres, academic cardiovascular investigators and thought leaders that includes the Duke Clinical Research Institute (DCRI); the Leuven Coordinating Centre, Belgium; the National Health and Medical Research Council Clinical Trials Centre and Flinders Medical Centre, Australia; the Green Lane Coordinating Center, New Zealand; the Uppsala Clinical Research Center in Sweden; the Trials ArgeNtina Group Organization (TANGO); the Estudios Cardiologicos Latino America (ECLA) in Argentina and the Brazilian Clinical Research Institute in São Paulo, Brazil.

Duke University, Durham, NC å Christopher B. Granger, MD, Associate Professor of Medicine; Division of Cardiology; Director, Cardiac Care Unit, Duke University Medical Center, Durham, NC å Robert A. Harrington, MD, Professor, Division of Cardiology; Director, Duke Clinical Research Institute, Durham, NC å Kerry L. Lee, PhD, Professor of Biostatistics and Informatics, Duke University Medical Center, Durham, NC å R. John Simes, MD, Professor of Clinical Epidemiology, Faculty of Medicine; Director, National Health and

More information about the nature of these collaborations

Medical Research Council (NHMRC) Clinical Trials Centre

can be gained in the following articles:

and Medical Oncologist Royal Prince Alfred Hospital,

å Topol EJ, Califf RM, Van de Werf F, Simoons M, Hampton J, Lee KL, White H, Simes J, Armstrong PW, for the VIGOUR

University of Sydney, Sydney, Australia å Frans Van de Werf, MD, PhD, Professor of Medicine,

Group. Perspectives on Large Scale Cardiovascular

Chairman, Department of Cardiology, University Hospital

Clinical Trials for the New Millennium. Circulation.

Gasthuisberg and head Leuven Coordinating Centre (LCC),

1997;95(4):1072-82. å Armstrong PW, Newby LK, Granger CB, Lee KL, Simes RJ, Van de Werf F, White HD, Califf RM, for the VIGOUR group. Lessons learned from a clinical trial. Circulation 2004:110:3610-3614. å Mark DB, Van de Werf FJ, Simes RJ, White HD, Wallentin LC, Califf RM, Armstrong PW for the VIGOUR Group.

The University of Gasthuisberg, Leuven, Belgium å Lars Wallentin, MD, PhD, Professor of Cardiology, Institution of Medical Sciences Cardiology, University Hospital, Uppsala, Sweden å Harvey White, MB, Director of Coronary Care & Green Lane Cardiovascular Research Unit; Green Lane Cardiovascular Service, Auckland, New Zealand

Cardiovascular Disease on a Global Scale: Deﬁning the Path Forward for Research and Practice Eur Heart J 2007; 28(21):2678-84. Epub 2007 Oct 16. å Califf RM, Armstrong PW, Granger CB, Harrington RA, Lee K, Simes RJ, Van de Werf F, Wallentin L, White HD for the Virtual Coordinating Centre for Global Collaborative Cardiovascular Research (VIGOUR) Organization. Toward a new order in cardiovascular medicine: Re-engineering through global collaboration. Eur Heart J. 2010;31:911917.

Annual Report — Two-thousand and Ten — Canadian VIGOUR Centre

Spectrum and Evolution: A Snapshot of CVC's Clinical Trial Experience 1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

1st SYMPHONY 2nd SYMPHONY

XaNADU pilot XaNADU ACS PACTS GUSTO ACS (IV) *

ADVANCE MI ASSENT II ASSENT III GUSTO III * VALIANT GUSTO AMI (V) * HERO II APLAUD

WATCH

EARLY ACS PARAGON B ** PURSUIT ***

XaNADU PCI APEX AMI ASSENT 3+ ASSENT IV PCI CAPTORS I CAPTORS II CARDINAL-COMMA CARDINAL-COMPLY ERASE-MI PREMIER WEST

* Previous GUSTO I, IIA, IIB prior to CVC establishment as centre, although Armstrong lead PI on these trials ** PARAGON A, prior to CVC establishment as centre although Armstrong lead PI on this trial *** PURSUIT commenced in 1995, prior to CVC's establishment as a centre PARADIGM commenced in 1995, prior to CVC's establishment as a centre

2009

2010

2011

2012

2013

2014

2015

2016

2017

Research spectrum

IMPROVE IT RADAR TRACER

Acute Coronary Syndrome

EXSCEL TECOS

Type 2 Diabetes

Acute Myocardial Infarction

Atrial ďŹ brillation STABILITY

ASCEND-HF & Sub-studies

Prevention Heart Failure

STREAM Myocardial Infarction

INNOVATE-PCI

Percutaneous Coronary Intervention

ST Elevation Myocardial Infarction

CVC Services

Biostatistics

The Canadian VIGOUR Centre provides a spectrum of clinical

å Development of statistical analysis plans and database

research based services including:

å Design of studies and sample size calculations speciﬁcations å Programming and validation of analysis databases and

Thought Leadership å Provide expert advice and promotion of cardiovascular

statistical tables, ﬁgures and listings å Advanced statistical analysis

research characterized by quality, scholarship and

å Development and application of novel statistical methods

integrity

Business Operations

å Deﬁne unmet needs for patients with and those at risk of cardiovascular disease å Align new cardiovascular research with these unmet needs å Seek cost effective solutions and enhance return on investment in research

Contract negotiations å Negotiations and management of agreements å Development and tracking of metrics å Invoicing & site payments Administration and Financial Management

Clinical Trial Operations

å Revenue/expense administration

Project management and clinical monitoring

å Performance management

å Investigator selection, qualiﬁcation, and recruitment å Investigative site start-up and training å Ensuring site regulatory compliance (i.e. Informed consent review for compliance with ICH requirements) å Monitoring of CRF completion, data collection, and query resolution å Expedited adverse-event reporting å On-site and in-house monitoring å Communication (Canadian Cardiac Chronicle Newsletter) Core ECG Laboratory å Facilitating trial design å Monitoring protocol adherence å ECG reading å Pathophysiologic insights

å Human resources management å Market and competitive landscape research å Information Systems (IS) planning management å Strategic planning å Process improvement å Quality Assurance å Training and Development Legal/ Institutional Liaise å Northern Alberta Clinical Trials & Research Centre (NACTRC) å University of Alberta å Alberta Health Services (AHS) å Duke Clinical Research Institute å Sponsors

å Assessment of prognosis and outcomes

CVC is dedicated to continuous quality assurance and

å Data management (data entry data collection, quality

diligently works with sites on timely and accurate data

control)

collection, collaborative problem solving and audit

Health Economics and Quality of life

preparedness. As an ARO, CVC routinely updates its

å Collection of resource utilization and cost data

Standard Operating Procedures (SOPs) and utilizes project

å Development of economic models

management principles for quality assurance. CVC employs

å Development of cost-effectiveness analyses

metrics to ensure that we deliver on commitments to our

Research

stakeholders and to identify areas for improvement.

Academic

CVC has access to an international group of clinical experts

å Trial architecture, development, data acquisition,

with experience in clinical research and access to a well-

integration, analysis, presentation and peer-review

established network of Canadian sites. We have some

publication

bilingual staff/ consultants and are sensitive to the linguistic

å Creation of novel substudies aimed at informing primary results and advancing knowledge

and cultural characteristics of our collaborative partners. Our work in clinical trials is both informed and enriched by

å Mentoring junior faculty, fellows and medical students

connectivity to regional, provincial and national registries

å Population health outcomes research

and population outcomes databases.

å Clinical registries development å Economic evaluation and cost-effectiveness å Quality of life & other patient outcomes

Canadian VIGOUR Centre — Two-thousand and Ten — Annual Report

"CVC is a proud member of the International VIGOUR group, a global collaboration of coordinating centers, academic cardiovascular investigators and thought leaders." —Paul W. Armstrong, MD

Uppsala Clinical Research Centre

Uppsala, Sweden

Leuven Coordinating Centre

Canadian

Leuven, Belgium

VIGOUR Centre

Edmonton, Canada

Duke Clinical Research Institute

Durham, USA

Estudios Clinicos Latinoamérica Rosario, Argentina

Green Lane

Brazilian Clinical

Coordinating Centre

Research Institute

São Paulo, Brazil Trials Argentine Group Organization

Buenos Aires, Argentina

Auckland, New Zealand Flinders Medical Centre

Adelaide, Australia National Health and Medical Research Council —Clinical Trials Centre

Sydney, Australia

Clinical Investigation, Project Management & Monitoring

Clinical Investigation, Project Management & Monitoring To date, the CVC has participated in over forty (40) cardiovascular clinical trials (Phase II and Phase III), with enrollment of over 260,000 patients globally, of which over 17,000 patients were from Canada. These patient enrollment ﬁgures consistently meet or exceed anticipated and representational enrollment relative to national populations of other countries around the world. CVC’s success in consistently meeting enrollment targets stems in large part from the strength of our relationships with our site network (more than 250 sites across Canada), comprised of over 440 principal investigators (PI’s). A key indicator and metric of our operational success and our ability to deliver on our promise of quality to each of our stakeholders is our ability to recruit sites to participate in multiple, noncompeting trials, and CVC is proud of the fact that over 200 PI’s have participated in more than one clinical trial with CVC. While this network includes cardiologists primarily, CVC has had participation from emergency physicians and internists as well as the recent involvement with endocrinologists. This evolving network reﬂects CVC’s foray into clinical trials involving diabetes with cardiovascular outcomes. In 2010 the CVC provided project management, site management and monitoring for 9 trials along with associated ancillary studies some of which are Canadian driven and developed by our faculty. The Clinical Operations group is comprised of 4 Project Managers/ Leads, 3 Site Management Coordinators, a monitoring lead, monitoring report reviewers and contracted monitors based regionally throughout the country. Our Project Managers/Leads are responsible for managing and overseeing their projects in Canada, reporting internally to the Manager of Clinical Operations and reporting externally to sponsors and academic partners. Additionally they work closely with sites throughout the trial to answer questions related to the protocol, data, study drug, etc, they monitor trends and issues associated with the trial, assess recruitment, ensure data quality and integrity is maintained, and track metrics to ensure project timelines and milestones being met.

Canadian VIGOUR Centre — Two-thousand and Ten — Annual Report

Part of CVC’s ongoing project management includes periodic publication of The Canadian Cardiac Chronicle which is distributed to investigative sites, our sponsors and international collaborators (Appendix 1 and http://www. vigour.ualberta.ca/). Our Site Management Coordinators work closely with the Project Managers/Leads to ensure regulatory is reviewed, logged and ﬁled appropriately, maintain databases with both demographic and trial related documentation, assist in getting sites through start-up, and communicate on a regular basis with the sites regarding recruitment, data and regulatory. Our Site Management Coordinators have a good overall understanding of the project(s) they are working on and provide short term coverage for the Project Lead if required. A summary of the nine trials and associated ancillary studies the CVC provided Canadian Clinical Operations support for in 2010 are summarized in the following pages.

Clinical Investigation, Project Management & Monitoring

Sponsored by Scios Inc, a Johnson & Johnson company,

As members of the Executive Committee and Steering

this phase III, randomized, double-blind, parallel-group,

Committee, Drs. Armstrong, and Ezekowitz respectively,

multicenter trial assessed the use of Nesiritide & standard

provided thought leadership associated with the ASCEND-

treatment compared to placebo and standard treatment

HF study. Dr. Ezekowitz was instrumental in the de

in patients with acute decompensated heart failure.

velopment and implementation of the following ancillary

ASCEND-HF completed enrollment in August 2010 with a

and/or parallel studies, associated with the ASCEND-HF trial;

total of 7142 patients randomized from over 25 countries

(1) Respiratory Sub-study, (2) Climate Sub-study, (3) Early

in the span of 3 years. Canada exceeded their projected

Process of Care/Registry Sub-study. Additionally, Padma

recruitment with 476 patients enrolled.

Kaul PhD led the Canadian Health Economic ancillary study to look at the cost associated with the hospitalization of

This trial now represents the largest acute decompensated

acute decompensated heart failure patients within Canada.

heart failure trial to date. On November 14, 2010 the

These ancillary studies have been further supplemented

ASCEND-HF results were presented by Dr. Adrian Hernandez

by a Canadian Heart Failure and Health Economic Registry,

from the Duke Clinical Research Institute (DCRI) at the

which retrospectively looks at the same patient population.

American Heart Association Conference (AHA) in Chicago,

With the trial now complete and the ﬁnal data being

Illinois at the late breaking clinical trial session (Circulation.

collected on the Canadian Heart Failure and Health Economic

2010;122:2217). The study revealed that (1) Nesiritide had

Registry, plans for presentations and publications of these

a modest effect on reducing dyspnea; and (2) was safe to

ancillary studies are planned for 2011.

administer and did not worsen renal function or mortality as had been suggested from prior overviews of smaller studies.

In addition to thought leadership, CVC provided overall

Much remains to be learned from this largest-ever study of

project management, site management and monitoring for

acute heart failure and it is anticipated that the results will

this trial and for the associated ancillary studies in Canada.

help further research to address the unmet needs of this important and growing patient population. Several projects relating to this rich database are currently in progress, some of which are being led by the CVC.

Nesiritide

Annual Report — Two-thousand and Ten — Canadian VIGOUR Centre

Clinical Investigation, Project Management & Monitoring

Co-sponsored by Amylin Pharmaceuticals, Inc. and Eli

The US has started recruitment and currently has enrolled

Lilly and Company, EXSCEL is a pragmatic, long-term,

30 patients with 42 sites activated. Canada is awaiting

placebo controlled, double-blinded multinational trial that

Health Canada submission approval to re-approach

will be conducted in approximately 400 sites worldwide

sites which previously indicated their sincere interest

and include an anticipated 9500 patients. This trial seeks

in participating and enrolling subjects in this study. We

to characterize the effects of Exenatide once weekly on

anticipate 25-30 Canadian sites will be enrolling by end

cardiovascular-related outcomes in patients with Type 2

of 2011. CVC’s scope includes project management, site

diabetes and is designed to compare the impact of including

management, and monitoring for all Canadian sites that

exenatide as part of usual care versus usual care without

participate in this trial.

exenatide on major cardiovascular outcomes. The CVC is pleased to be collaborating with Dr. Shaun Goodman, who will represent Canada on the Operations Committee for this trial along with Dr. Jean-Francois Yale. This trial is beginning to get underway, and is anticipated to be completed in 2017.

Exenatide is a synthetic compound derived from a hormone found in the saliva of the Gila monster. It has an impact on the secretion of insulin and glucagon and gastric emptying. The sequence of this polypeptide is:

H-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-PheIle-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2

Canadian VIGOUR Centre — Two-thousand and Ten — Annual Report

Clinical Investigation, Project Management & Monitoring

Sponsored by Merck & Co. Inc., this trial is a multicenter, double-blind, randomized study to establish the clinical beneﬁt and safety of Vytorin (Ezetimibe/Simvastatin tablet) versus Simvastatin monotherapy in high-risk patients presenting with acute coronary syndrome (ACS). Initiated in 2005, this is a phase IV study to evaluate the clinical beneﬁt of Ezetimibe/Simvastatin combination compared with simvastatin in 18,000 stabilized acute coronary syndrome subjects worldwide. On July 8, 2010 the study completed enrollment with a total of 18,143 subjects randomized. Canadian sites contributed a total of 1,106 subjects with 602 coming from sites managed by the CVC. Follow-up is now expected to continue for a minimum of 2.5 years from the date of the last patient enrolled. Dr. Armstrong is a member of the international Steering Committee. The CVC provides project management, site management and monitoring for over 30 Canadian sites.

Ezetimibe

Annual Report — Two-thousand and Ten — Canadian VIGOUR Centre

Clinical Investigation, Project Management & Monitoring

Sponsored by Portola Pharmaceuticals Inc. this is a

and more rapid antiplatelet effect than Clopidogrel during

randomized, double-blind phase II study looking at the

both the acute and chronic phases of therapy, no excess

safety and efﬁcacy of Elinogrel, a novel, intravenous and

TIMI major or minor bleeding at the 24 hour or 120 day

oral P2Y12 inhibitor, in non-urgent percutaneous coronary

time points was seen and the adverse events (while similar

intervention (PCI). Enrollment concluded in November 2009

in both the Elinogrel and Clopidogrel arms) did show

with a total of 652 patients randomized from 5 countries.

more frequent dyspnea and excess in transaminase in the

Canada contributed 132 (20%) patients in this trial from

Elinogrel arms.

12 sites across the country, ranking second in enrollment contributions only to the United States.

Dr. Robert Welsh acted as the Co-Principal Investigator/ Chair for this study and was actively involved in protocol

The INNOVATE-PCI trial was accepted and presented on

development and guidance throughout the trial. CVC

August 30, 2010 at the European Society of Cardiology

provided project management, site management and

Congress Hotline session in Stockholm, Sweden by

monitoring for this trial.

Dr. Sunil Rao from the Duke Clinical Research Institute (DCRI) (http://assets.escardio.org/webcasts/default. aspx?id=ESC2010/2036) The key results revealed that both intravenous and oral Elinogrel resulted in a greater

INNOVATE-PCI Trial Design

Canadian VIGOUR Centre — Two-thousand and Ten — Annual Report

Clinical Investigation, Project Management & Monitoring

Sponsored by Regado Biosciences, this is a randomized,

Dr. Paul Armstrong sits on the Advisory Board for

partially-blinded, multicenter, active-controlled, dose-

this study. The CVC provides overall Canadian project

ranging study assessing the safety, efﬁcacy and

management, site management and monitoring for the

pharmacodynamics of the REG1 anticoagulation system

trial. Additionally, the CVC has worked closely with Dr.

compared to unfractionated Heparin or low molecular

Christopher Buller, the Canadian member of the Steering

weight Heparin in subjects with acute coronary syndrome.

Committee for this trial, who is based out of the Hamilton Health Sciences Centre.

Following thirteen months of patient recruitment which achieved 640 of the expected 800 patients from 5 countries, enrollment concluded unexpectedly in October 2010 due to a few serious adverse events requiring further investigation. However, the data collected until recruitment was halted was deemed sufﬁcient and the trial was accepted for presentation at the late breaking sessions during the upcoming American College of Cardiology meetings in New Orleans, Louisiana on April 3, 2011.

Mechanism of action

Annual Report — Two-thousand and Ten — Canadian VIGOUR Centre

Our teamâ&#x20AC;&#x201D;picture taken March 2, 2010â&#x20AC;&#x201D;along with the CVC Faculty and leadership team are instrumental in establishing and nurturing a nati Back Row: Monica Adam, Valencia Galbraith, Carla Price, Heather Good, Yinggan (Gray) Zheng, Becky Leung, Jeffrey Bakal, Pushpa Jagasia, J

Francine Heatley, Francis Cheung, Lyndsey Garritty; Front Row: Dianne Payeur, Dr. Robert Welsh, Dr. Cynthia Westerhout, Dr. Paul Armstrong,

ional network of clinical investigators and nurse coordinators who are fundamental to the successful conduct of cardiovascular clinical trials.

0-An Padberg, Vaneeta Mishra, Christie Sorochuk, Dr. Yuling Fu, Subrata Datta, Karine Betts, Catharine Robinson, Karen Buck, Hany Siha,

, Dr. Padma Kaul, Dr. Justin Ezekowitz, Tracy Temple.

Clinical Investigation, Project Management & Monitoring

Sponsored by GlaxoSmithKline, this trial is a randomized, placebo-controlled, double-blind, parallel group, multicenter, event-driven clinical outcomes study of Darapladib versus placebo in subjects with chronic coronary heart disease to compare the incidence of major adverse cardiovascular events. With the ﬁrst patient randomized in December 2008 and the participation of 38 countries, enrollment progressed rapidly with 15,839 patients being enrolled over a 10 month period, which exceeded initial projections. After enrolling an expected 779 patients, Canadian enrollment was capped in August 2009. The CVC was responsible for the site start-up of 38 Canadian sites, and continues to provide ongoing regulatory maintenance in addition to working with the sponsor on patient retention strategies and standard of care reporting. Dr. Paul Armstrong is actively involved as a member of the Steering Committee on this trial. Currently study management is focused on ensuring patients are retained in the trial and that their medical treatment is optimized such that the ﬁnal result will be relevant to contemporary patient care.

Darapladib

Canadian VIGOUR Centre — Two-thousand and Ten — Annual Report

Clinical Investigation, Project Management & Monitoring

Sponsored by Boehringer Ingelheim, this trial is a

therapy for acute myocardial infarction patients versus

comparison of the efﬁcacy and safety of a strategy

primary PCI. Additionally he is co-chair on the Executive

of early ﬁbrinolytic treatment with Tenecteplase and

Committee for STREAM.

additional antiplatelet and antithrombin therapy followed by catheterization within 6-24 hours of rescue coronary

Dr. Robert Welsh has been involved as the Canadian

intervention versus a strategy of standard primary

National Lead on the Steering Committee for this trial as

percutaneous coronary intervention (PCI) in patients with

well as participating as one of the active and recruiting

acute myocardial infarction within 3 hours of onset of

sites in Canada. In collaboration with Dr. Paul Armstrong,

symptoms.

he has developed and led a Canadian speciﬁc sub-study, “The STrategic Reperfusion Early After Myocardial

With the commencement of enrollment in 2008, over 1,000

infarction (STREAM) anticoagulation with Enoxaparin vs.

patients have been enrolled globally with an anticipated

unfractionated Heparin in primary PCI sub-study.”

ﬁnal enrollment of 2000 by March 2012. To date Canada has contributed 78 patients from 2 pre-hospital sites and 1

The CVC has provided overall project management, site

community site.

management and monitoring in Canada for this trial.

Following the success of the CVC-initiated WEST trial, Dr.

The CVC ECG Core Laboratory has been actively involved

Armstrong was on the Scientiﬁc Advisory Committee to

in the analysis of ECG’s for the STREAM study. This work is

develop this new protocol testing the use of pre-hospital

described later in this report.

Tenecteplase Annual Report — Two-thousand and Ten — Canadian VIGOUR Centre

Clinical Investigation, Project Management & Monitoring

Sponsored by Merck & Co. Inc., this is a randomized, placebo controlled clinical Trial to Evaluate Cardiovascular Outcomes after treatment with Sitagliptin (TECOS) in patients with Type 2 diabetes mellitus and inadequate glycemic control. This trial has taken CVC into the therapeutic area of endocrinology which both broadened our site network and opened up a new area for clinical research. With a target enrollment of 14,000 patients globally, just over 5,000 have been recruited by the end of 2010 with a contribution of 190 patients from Canada’s 22 enrolling sites. Dr. Paul Armstrong is a member of the Executive Committee for this trial. The CVC provides overall project management, site management and monitoring for TECOS. Additionally a unique collaboration as it relates to site communications and trial issues/updates has been established between the CVC and Dr. Irene Hramiak, Professor of Medicine and Chair of Division of Endocrinology and Metabolism, University of Western Ontario.

Sitagliptin

Canadian VIGOUR Centre — Two-thousand and Ten — Annual Report

Clinical Investigation, Project Management & Monitoring

Sponsored by Merck & Co. Inc., this trial is a multicenter, randomized, double-blind, placebo-controlled study evaluating the safety and efﬁcacy of adding a new thrombin receptor antagonist (Vorapaxar) to the standard of care for a minimum of 1 year in patients with non-ST-segment elevation acute coronary syndrome. Following 30 months of recruitment, TRACER completed enrollment on June 9, 2010 with 12,642 patients enrolled globally from 812 sites, reﬂecting a Canadian contribution of 573 patients from 27 sites. In the year ahead there is much work to be done with patient follow-up and retention, data cleaning, database lock and presentation and publication. The CVC has provided overall project management, site management and monitoring for this trial. Recognizing that ECG changes are the basis for patient inclusion, and accurate ECG assessment was a critical component of this trial, the CVC’s ECG Core Lab has been actively involved in assessing patients with negative markers to ensure they were enrolled in accordance with the protocol. Dr. Armstrong also serves an active member of the Executive Committee for TRACER.

Vorapaxar - A potent selective thrombin receptor antagonist (TRA) found in the bark of the Australian Rhododendron.

Annual Report — Two-thousand and Ten — Canadian VIGOUR Centre

ECG Core Laboratory

ECG Core Laboratory The Canadian VIGOUR Centre ECG Core Laboratory has extensive research in the evaluation and interpretation of ECG’s, analyzing over 178,974 ECG’s since its inception in 1998 and has provided consistently high quality output for 13 clinical trials. The main ECG core lab projects for 2010 were related to PLATO, TRACER, and STREAM. As of the end of December 2010, ECG’s for 1019 STREAM patients had been received. Because of the nature of the submission of these ECG’s, this reﬂects that at least one of the protocol ECG’s was uploaded for those patients. For this PLATO (PLATelet Inhibition and Patient Outcomes) a study

same time frame, 662 patients had their full set of ECG’s

sponsored by AstraZeneca and was a large, prospective,

submitted.

multicenter, randomized, double-blind, event-driven trial comparing ticagrelor versus clopidogrel for reduction of 1

PROACT

year cardiovascular events in patients with acute coronary

Late in 2010, the CVC received grant funding to pursue the

syndrome with or without ST-segment elevation. CVC core

PROACT project, which is detailed in a later section in this

lab was awarded the opportunity to systemically assess

report, entitled “Future research”. A key component of this

over 15,000 patients’ PLATO ECGs which provides us with

project is the timely recognition of patients needs, and how

a unique opportunity to examine possible modulation of

best to direct health resources for better and more efﬁcient

treatment effect via quantitative analyses of ST-T changes

patient care. Our ECG Core Lab will play a signiﬁcant role

and Q duration between admissions and discharge ECGs.

in analyzing the ECG’s derived from this project, which will

Moreover, PLATO allowed us to determine the relative

contribute to a database sure to be rich in information about

contribution of the ECG in predicting the clinical outcome in

how local Edmonton patients fare with current practices,

the presence of the contemporary risk markers for reﬁned

and how we can change current practices and redirect

prognostication and risk stratiﬁcation of ACS patients. The

health care resources to improve patient outcomes for those

ECG Core lab team ﬁnished analyzing 15,563 patient ECGs

suffering from heart disease.

in December and this unique dataset will provide new opportunities for insight into the PLATO study outcomes as well as helping to plan appropriate future studies.

Other ECG Activities Mandatory quality programs for CVC ECG Core Laboratory have expanded from assuring the accuracy and precision of key ECG parameters to now including a complex process combination of evolving process, and data veriﬁcation in the collection, evaluation, transforming the hard copies ECG images to electronic scanned images and management of data entry ﬁles.

The CVC ECG Core Laboratory has been actively involved in the analysis of ECG’s for the Strategic Reperfusion Early After Myocardial Infarction (STREAM) trial which has included, but is not limited to, the determination of ST deviation (area at risk), ST resolution (as marker of myocardial reperfusion) and QRS Scoring (for infarct size) in patients experiencing acute myocardial infarction (AMI). They have also provided central adjudication in patients with rescue PCI to determine if they have met the clinical indication for this procedure.

Training of our ECG Core Laboratory personnel is essential with consistent review of procedures and methodology. Consistency in measurements is maintained through intensive ongoing training, detailed and global standard operating procedures. Inter-and Intra –observer variability tests are used to monitor accuracy for data collected from the ECG core readers. Our aim is translating research results into information useful for clinical applications. By using the ECG parameters to generate an improved understanding of the path physiologic processes involved in ACS and use that understanding to enable improvements in managing cardiac patient, prediction of outcome and to stimulate further cardiovascular scientiﬁc research

Canadian VIGOUR Centre — Two-thousand and Ten — Annual Report

ECG Core Laboratory

Activities of the ECG Core Laboratory

WEST

STREAM ECGs read: 5,092

ECGs read: 1,968

APEX-AMI ECGs read: 17,061

PURGE ECGs read: 4,380

PLATO ECGs read: 25,557

PARAGON B ECGs read: 4,576

Total electrocardiograms read: 178,974

GUSTO ACS IV ECGs read: 7,757

ASSENT II ECGs read: 50,847

GUSTOII b ECGs read: 24,284

CAPTORS II ECGs read: 1,816

ASSENT IV PCI ECGs read: 6,668

ASSENT III ASSENT 3+

ECGs read:24,380

ECGs read: 6,556

Annual Report — Two-thousand and Ten — Canadian VIGOUR Centre

Academic Research Projects from Clinical Trials and Population Health Laboratory

the protocol, audits physicians’ performance in the trial, and independently analyzes the data. Every clinical trial managed by the CVC is registered in the public domain and published in the peer-reviewed literature. CVC’s Academic Research Group generates peer-reviewed publications from intellectual conception to statistical

The CVC Research Group undertakes innovative clinical

analysis and manuscript construction. Presentation of such

research in cardiovascular medicine in collaboration with

ﬁndings is regularly made at national and international

local, national, and international researchers. Their research

scientiﬁc meetings. The CVC "team approach" engages

focuses on the assessment of patient, environmental and

clinician scientists, epidemiologists/biostatisticians and other

process-of-care factors and their association with outcomes

vested parties. In so doing it remains true to the core value

in patients with acute coronary syndromes, acute and

of providing novel insights that facilitate health practitioners

chronic heart failure, cardiac arrest, arrhythmias, and

to advance cardiovascular care.

diabetes. Areas of interest include: international and regional

differences, time to treatment, use of pharmacologic and

Some highlights of academic work based on clinical trials

mechanic interventions, availability of onsite interventional

from the past year include:

facilities, resource utilization, and gender/sex and age

å In collaboration Drs. Toma, Westerhout, Fu and Armstrong

differences in early discharge and clinical outcomes.

and others observed that PCI in non-infarct coronary

Developing and validating prognostic models and tools for

vessels was performed coincident with primary PCI in approximately 1

risk stratiﬁcation is also

Peer Reviewed Publications

a major emphasis, and

in 10 STEMI patients with multi-vessel

Full articles

Abstracts

often incorporates data

coronary artery disease

generated by the CVC ECG Core Laboratory.

despite guidelines that

discourage this practice.

There are two main

These patients had

data sources on which

signiﬁcantly increased

academic research

mortality. (Eur Heart J.

projects are based:

2010;31:1701-1707)

(i) clinical trials and

and others observed

databases and registries. The CVC

that early ﬁbrinolysis

was associated with

houses databases

a reduction in 1-year

from 22 clinical trials, which have enrolled

Drs. Westerhout,

Welsh, Armstrong

(ii) population-based

mortality compared to

more than 192,116

2006

2007

2008

2009

2010

primary PCI in early presenters with STEMI

patients. Quantitative electrocardiographic data have been collected in over

in the CAPTIM and WEST trials. They concluded that time

69,403 patients by the ECG Core Laboratory. Population-

from symptom onset should be a key consideration when

based data are available for all cardiovascular patients in

selecting reperfusion therapy for these patients (Am

the Province of Alberta seeking medical care between 1999 and 2009, the Vital Heart Response registry (approximately

Heart J. 2011;161:283-90) å Drs Welsh, Westerhout, Armstrong and others observed

3500 at end of 2010 - 750 patients/year since 2006),

that 2.2% STEMI patients undergoing primary PCI had a

Providing Rapid Out of Hospital Acute Cardiovascular

history of previous coronary artery bypass grafts (CABG).

Treatment study (PROACT n=580) and ASCEND-HF, a nested

Patients with prior CABG were less likely to undergo acute

registry (n=700).

reperfusion, had worse angiographic outcomes following primary PCI, and had higher 90-day mortality than those

Clinical Trials Research In collaboration with industry and other sponsors, the CVC contributes to the design of study protocols, recruits physicians from across the country to perform

Canadian VIGOUR Centre — Two-thousand and Ten — Annual Report

without prior CABG. These ﬁndings are especially relevant when the infarct-related artery was a bypass graft. (JACC

Interventions. 2010;3:343-351).

Research Training & Continuing Medical Education

Continuing Medical Education

Research Trainees

Beyond 2000 (XVI) New Concepts in Acute Coronary

The CVC has been active in providing clinical research and trial experience for a number of trainees including; Cardiology residents:,Osama al-Hadramy, MD; Sean van Diepen, MD; Osama Alhadramy, MD; Mustafa Toma, MD; Kevin Bainey, MD, Mohammed Almansori, MD; Mike McDonald, MD; Michael C Tjandrawidjaja, MD and Olga Toleva, MD plus and an Internal Medicine resident Kebbie Josan, MD. A Master’s student Nawaf Almajed, MBBS supervised by Justin Ezekowitz started a residency in Internal Medicine in 2010. CVC also had a medical student,

Dr. Armstrong ably assisted by Jo-An Padberg played a signiﬁcant role in developing and leading a University of Alberta sponsored continuing medical education (CME) major satellite session for the 16th consecutive year. Syndromes symposium on Sunday, October 24, 2010 in Montreal in conjunction with the Canadian Cardiovascular Society’s Annual General Meeting (co-sponsored with an unrestricted educational grant from sanoﬁ-aventis Canada and Bristol-Myers Squibb Canada, and Merck Frosst Canada Ltd. and Merck Pharmaceuticals.). This was attended by approximately 600 delegates and remains of one of the most highly regarded and best attended satellite symposiums of the Canadian Cardiovascular Congress (CCC). (For program details see Appendix 2).

Debraj Das, involved in research training in the summer of 2010; he presented his research ”Insights acquired from Q-waves on the Basleine ECG of Patients Presenting with ST Segment Elevation Myocardial Infarction” at the Faculty of Medicine & Dentistry's 43rd Annual Summer Students' Research Day.

"It is difficult to imagine undertaking

"The Canadian VIGOUR Centre has

training in cardiovascular medicine

played an instrumental role in my

without getting one's feet wet in

future goal to become a clinician-

research. It is more difficult still

scientist in Alberta. Not only

to imagine pursuing meaningful,

has Dr. Armstrong and the CVC

rigorous research without the

shown me the struggles and

resources, access, collaboration,

tremendous rewards of clinical

and education provided to trainees

research, I have gained a great

within the VIGOUR group. Under

deal of knowledge on how to

the guidance and mentorship of Dr.

manage a project from the initial

Armstrong, I am fortunate to have

research question to the ﬁnal

enjoyed an invaluable experience in

manuscript. VIGOUR has given me

clinical research training from my

the support to jump start my medical

time as a medical student to now as a

career and the stepping stones

cardiology resident."

towards a bright future."

—Michael Tjandrawidjaja, MD

—Debraj Das

Cardiology trainee

Summer student

Annual Report — Two-thousand and Ten — Canadian VIGOUR Centre

Sources of Clinical Trial Revenue

Clinical Operations *In Canadian dollars, includes pass-throughs and exchange rate adjustments

7%, ASCEND-HF Sponsor: Johnson & Johnson and Jansen Ortho Inc. in conjunction with Duke Clinical Research Institute

34%, TRACER Sponsor: Merck in conjunction with Duke Clinical Research Institute

24%, IMPROVE-IT Sponsor: Merck in conjunction with Duke Clinical Research Institute

8%, INNOVATE-PCI Sponsor: Portola Pharmaceutical Inc.

15%, TECOS

1%, PLATO

Sponsor: Merck & Co. Inc.

Sponsor: AstraZeneca in

in conjunction with Duke

conjunction with Uppsala

Clinical Research Institute

Clinical Research Center

4%, STREAM

4%, STABILITY

Sponsor: Boehringer

3%, RADAR

Sponsor: GlaxoSmithKline

Ingelheim, Hoffmann LaRoche

Sponsor: Regado

in conjunction with

& Sanoﬁ-aventis Canada Inc.

Biosciences Inc.

VIGOUR partners

in conjunction with Leuven Coordinating Centre.

Canadian VIGOUR Centre — Two-thousand and Ten — Annual Report

Awards, Honours and Grants

"The work of many talented people who together in a synergistic fashion complement our efforts at discovery and learning, all in support of enhanced cardiovascular care."

In 2010, Dr. Armstrong was elected for Fellowship in the Royal Society of Canada and Drs. Armstrong, Welsh and Kaul were honoured in the University of Alberta’s annual Celebration of Research and Innovation. Dr. Ezekowitz holds an Alberta Innovates – Health Solutions Population Health Investigator Award, a CIHR New Investigator Award and a Heart and Stroke Foundation of Canada New Investigator Award. Dr. Kaul holds an Alberta Innovates – Health Solutions Population Health Investigator Award. Debraj Das received a Summer Studentship award from Alberta Innovates – Health Solutions for his research with Dr.

—Dr. Paul Armstrong

Armstrong and CVC.

Grant Funding Project

Sponsor(s)

Grant Holders

Term

Providing Rapid Out

Mazankowski Alberta Heart

Paul Armstrong (PI),

2010—2012

of Hospital Acute

Institute

Justin Ezekowitz,

Cardiovascular Treatment

Padma Kaul,

(PROACT)

Finlay McAlister, Robert Welsh

Tracking Gender Differences

Canadian Institutes of Health

Padma Kaul (PI),

in Acute Coronary

Research

Paul Armstrong,

Syndromes: At the First

Michelle Graham,

Point of Care and Beyond

Colleen Norris,

2008—2011

Robert Welsh Team grant:

Faculty of Medicine/Capital

E. Ryan (PI),

Vascular complications

Health Emerging Research

Padma Kaul,

associated with gestational

Team Grants Competition

S Davidge

Acute Heart Failure –

Canadian Institutes of Health

Justin Ezekowitz

2009 to 2012

Emergency Management

Research

Team Grant: Diastolic Heart

Alberta Innovates- Health

Jason Dyck (PI),

2009—2014

Failure

Solutions

Todd Anderson,

2008—2011

diabetes mellitus in Alberta

Justin Ezekowitz Cardiac Chemoreceptors in Heart Failure

Heart and Stroke Foundation

Michael Stickland (PI),

2009—2012

Justin Ezekowitz

Annual Report — Two-thousand and Ten — Canadian VIGOUR Centre

Future Research

Future Research Providing Rapid Out of Hospital Acute Cardiovascular Treatment (PROACT) Our group of researchers has contributed to substantially improve the way heart attack patients are treated in Alberta. We have introduced a variety of changes in the process of care which has improved patients’ chances of surviving. We now intend to investigate how best to improve care of patients with other life threatening acute heart disease including heightened risk of heart attack and heart failure. These diseases are sensitive to timely treatment and appropriate referral to the institution best equipped to address their underlying problem. Preliminary funding for this project was received in 2010 and an important feature of the research will be to explore new ways of assessing those individuals at highest risk and greatest need to ensure they are cared for more promptly and efﬁciently than before. This project will initially be conducted in metropolitan Edmonton and will involve studying the care provided to these patients currently; identifying current gaps in the diagnosis, treatment and triage; developing new methods to identify those patients at high risk who beneﬁt most from expedited care; and studying the results changes in process have on patients and costs.

Canadian VIGOUR Centre — Two-thousand and Ten — Annual Report

Publications—2010

2010;3(1):52-60. With accompanying editorial by Gibson CM and Pride YB. Myocardial infarct size reduction with

CVC faculty are frequently senior authors on papers in top-

pexelizumab. JACC Cardiovascular Imaging. 2010;3(1):61-

tier journals.

63. Armstrong PW. Intracoronary streptokinase in acute myocardial infarction. Nature Reviews Cardiology. 2010;7:67-69. Trendelenburg M, Theroux P, Stebbins A, Granger C, Armstrong P, Pfisterer M. Influence of functional deficiency of complement mannose-binding lectin on outcome of patients with acute ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention.

Eur Heart J. 2010;30(10):1181-1187. Lopes RD, Starr A, Pieper CF, Al-Khatib SM, Newby LK,

Peer reviewed articles Tjandrawidjaja MC, Fu Y, Westerhout CM, White HD, Todaro TG, Van de Werf F, Mahaffey KW, Wagner GS, Granger CB, Armstrong PW on behalf of the APEX-AMI Investigators. Resolution of ST-segment depression: A new prognostic marker in ST-segment elevation myocardial infarction.

Eur Heart J. 2010;31:573-581. Reproduced in Asia-Africa Excerpted Edition (4(4)) and Russian Excerpted Edition (4(4)). Reproduced in Korean Excerpted Edition. Berger JS, Roe MT, Gibson CM, Kilaru R, Green CL, Melton L, Blankenship JD, Metzger DC, Granger CB, Gretler DD, Grines CL, Huber K, Zeymer U, Buszman P, Harrington RA, Armstrong PW. Safety and feasibility of adjunctive antiplatelet therapy with intravenous elinogrel, a directacting and reversible P2Y12 ADP-receptor antagonist, before primary percutaneous intervention in patients with ST-elevation myocardial infarction: The early rapid reversal of platelet thrombosis with intravenous elinogrel before PCI to optimize reperfusion in acute myocardial infarction (ERASE MI) pilot trial. Am Heart J. 2009; 58(6):998-1004. e1. French JK, Hellkamp AS, Mahaffey KW, Cohen E, Kleiman NS, O’Connor CM, Holmes DR, Hochman JS, Granger CB, Armstrong PW. Mechanical complications postpercutaneous coronary intervention in ST elevation myocardial infarction – From APEX-AMI. Am J Cardiol. 2010;105: 59-63. Patel M, Armstrong PW, Stebbins A, Worthley SG, Dill T, Rademakers FE, Velleti U, Barsness G, Van de Werf F, Hamm CW, Granger CB, Kim RJ. Pexelizumab and infarct size in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention: A delayed enhancement cardiac magnetic resonance substudy from the APEX-AMI trial. JACC Cardiovascular Imaging.

Canadian VIGOUR Centre — Two-thousand and Ten — Annual Report

Mehta RH, Van de Werf F, Mahaffey KW, Armstrong PW, Harrington RA, White HD, Wallentin L, Granger CB. Warfarin use and outcomes in patients with atrial ﬁbrillation complicating acute coronary syndromes. Am J Med. 2010;123:134-140. Jarai R, Huber K, Bogaerts K, Droogne W, Ezekowitz J, Granger CB, Sinnaeve PR, Ross AM, Zeymer U, Armstrong PW, Van de Werf FJ on behalf of the ASSENT IV-PCI investigators. Plasma NT-proBNP concentrations in relation to time-to-treatment and TIMI ﬂow: A substudy of the ASSENT IV-PCI trial. Am Heart J. 2010;159:131-140. Montalescot G, Ellis SG, de Belder MA, Janssens L, Katz O, Pluta W, Ecollan P, Tendera M, van Boven AJ, Widimsky P, Andersen HR, Betriu A, Armstrong PW, Brodie BR, Herrmann HC, Neumann FJ, Effron MB, Lu J, Barnathan ES, Topol EJ on behalf of the FINESSE investigators. Enoxaparin in primary and facilitated percutaneous coronary intervention: A formal prospective non-randomized substudy of the FINESSE trial. JACC Interventions. 2010;3:203-212. Welsh RC, Granger CB, Westerhout CM, Blankenship JC, Holmes DR Jr., O’Neill WW, Hamm, CW, Van de Werf F, Armstrong PW on behalf of the APEX AMI Investigators. Prior coronary artery bypass graft patients with STsegment elevation myocardial infarction treated with primary percutaneous coronary intervention. JACC

Interventions. 2010;3:343-351. Ohman EM, Roe MT, Armstrong PW, Fox KA, Prabhakaran D, White HD. Public sensationalism and clinical trials: How to address the challenges of science? Am J Med. 2010;123(6):481-483. Califf RM, Armstrong PW, Granger CB, Harrington RA, Lee K, Simes RJ, Van de Werf F, Wallentin L, White HD for

Publications—2010

the Virtual Coordinating Centre for Global Collaborative

K, Scheller B, Armstrong PW, Di Mario C. Early routine

Cardiovascular Research (VIGOUR) Organization. Toward

percutaneous coronary intervention after ﬁbrinolysis

a new order in cardiovascular medicine: Re-engineering

versus standard therapy in ST-segment elevation

through global collaboration. Eur Heart J. 2010;31:911-

myocardial infarction: A meta-analysis. Eur Heart J.

917.

2010;31(17):2156-2169. Chin CT, Roe MT, Fox KAA, Prabhakaran D, Marshall DA,

Alhadramy O, Westerhout CM, Brener SJ, Granger CB,

Petitjean H, Lokhnygina Y, Brown E, Armstrong PW, White

Armstrong PW for the APEX-AMI Investigators. Is visual

HD, Ohman EM on behalf of the TRILOGY ACS Steering

interpretation of coronary epicardial ﬂow reliable in

Committee. Study design and rationale of a comparison of

ST-elevation myocardial infarction patients undergoing

prasugrel and clopidogrel in medically managed patients

primary angioplasty? Insights from the angiographic sub-

with unstable angina/non-ST-segment elevation myocardial

study of the APEX-AMI Trial. Am Heart J. 2010;159:899-

infarction: The Targeted Platelet Inhibition to Clarify the

904.

Optimal Strategy to Medically Manage Acute Coronary

Van Diepen S, Siha H, Fu Y, Westerhout CM, Lopes RD,

Syndromes (TRILOGY ACS) Trial. Am Heart J. 2010;160:16-

Granger CB, Armstrong PW for the APEX AMI Investigators.

22.e1.

Do baseline atrial electrocardiographic and infarction patterns predict new onset atrial ﬁbrillation after STelevation myocardial infarction? Insights from the APEXAMI Trial. (J Electrocardiol. 2010;43(4):351-358. Huber K, Holmes DR Jr., van’t Hof AW, Montalescot G, Aylward PE, Betriu GA, Widimsky P, Westerhout CM, Granger CB, Armstrong PW. Use of glycoprotein IIb/IIIa inhibitors in primary percutaneous coronary intervention: Insights from the APEX-AMI Trial. Eur Heart J. 2010;31:1708-1716. Reproduced in Indian Excerpted Edition. Toma M, Buller CE, Westerhout CM, Fu Y, O’Neill WW, Holmes DR Jr., Hamm CW, Granger CB, Armstrong PW for the APEX-

Armstrong PW, Gershlick A, Goldstein P, Wilcox R, Danays

AMI Investigators. Non-culprit coronary artery PCI during

T, Bluhmki E, Van de Werf F on behalf of the STREAM

acute ST-segment elevation myocardial infarction: Insights

Steering Committee. The Strategic Reperfusion Early

from the APEX-AMI Trial. Eur Heart J. 2010;31:1701-1707.

After Myocardial infarction (STREAM) study. Am Heart J.

Reproduced in Indian Excerpted Edition.

2010;160:30-35.e1.

Almansori M, Armstrong PW, Fu Y, Kaul P.

Ezekowitz JA, Armstrong PW, Granger CB, Theroux P,

Electrocardiographic identiﬁcation of the culprit coronary

Stebbins A, Kim RJ, Patel MR. Predicting chronic left

artery in inferior ST elevation myocardial infarction. Can J

ventricular dysfunction 90 days after ST-segment elevation

Card. 2010;26(6):293-296.

myocardial infarction: An assessment of pexelizumab in acute myocardial infarction (APEX-AMI) substudy. Am

Eggers KM, Armstrong PW, Califf RM, Simoons ML, Venge

Heart J. 2010;160:272-278.

P, Wallentin L, James SK. ST2 and mortality in non-ST segment elevation acute coronary syndrome. Am Heart J.

Tjandriawidjaja MC, Fu Y, Westerhout CM, Wagner GS,

2010;159:788-794.

Granger CB, Armstrong PW on behalf of the APEX-AMI Investigators. Usefulness of the QRS score as a strong

Simes RJ, O’Connell RL, Aylward PE, Varshavsky S, Diaz R,

prognostic marker in patients discharged after undergoing

Wilcox RG, Armstrong PW, Granger CB, French JK, Van de

primary percutaneous coronary intervention for ST-

Werf F, Marschner IC, Califf R, White HD for the HERO-2

segment elevation myocardial infarction. Am J Cardiol.

Investigators. Unexplained international differences in

2010;106:630-634.

clinical outcomes after acute myocardial infarction and ﬁbrinolytic therapy: Lessons from the HERO-2 Trial. Am

Jarai R, Huber K, Bogaerts K, Sinnaeve PR, Ezekowitz J,

Heart J. 2010;159:988-997.

Ross AM, Zeymer U, Armstrong PW, Van de Werf FJ on behalf of the ASSENT-IV PCI Investigators. Prediction of

Borgia F, Goodman SG, Halvorsen S, Cantor WJ, Piscione F,

cardiogenic shock using plasma Nt-proBNP concentrations

Le May MR, Fernandez-Aviles F, Sanchez PL, Dimopoulos

in ST-elevation myocardial infarction: An analysis from the

Annual Report — Two-thousand and Ten — Canadian VIGOUR Centre

Publications—2010

ASSENT-IV PCI Trial. Crit Care Med. 2010;38(9):1793-1801.

PW, White HD, Topol EJ, Califf RM, Ohman EM. Association of mortality with years of education in patients with ST

Armstrong PW, Ezekowitz JA. (Editorial) Testosterone

elevation myocardial infarction treated with ﬁbrinolysis.

therapy in women with heart failure – Why can’t a woman

JACC Cardiovascular Outcomes. 2010;57:138-146.

be more like a man? J Am Coll Cardiol. 2010;56(16):13171318.

Oreopoulos A, Kalantar-Zadeh K, McAlister FA, Ezekowitz JA, Fonarow GC, Johnson JA, Norris CM, Padwal RS.

Kaul P, McAlister FA, Ezekowtiz JA, Bakal JA, Curtis LH, Quan

Comparison of direct body composition assessment

H, Knudtson ML, Armstrong PW. Resource use in the last 6

methods in patients with chronic heart failure. J Card Fail.

months of life among patients with heart failure in Canada.

2010 Nov;16(11):867-72.

Arch Int Med. 2010 (doi:10.1001/archinternmed.2010.365) Massie BM, O’Connor CM, Metra M, Ponikowski P, Teerlink Toma M, Fu Y, Ezekowitz JA, McAlister FA, Westerhout CM,

JR, Cotter G, Weatherley BC, Cleland JG, Givertz MM,

Granger CB, Armstrong PW for the APEX-AMI Investigators.

Voors A, DeLucca P, Mansoor GA, Salemo CM, Bloomﬁeld

Does silent myocardial infarction add prognostic value

DM, Dittrich HC, PROTECT Investigators and Committees;

in ST-elevation myocardial infarction patients without a

Rolofylline, an adenosine A1-receptor antagonist, in acute

history of prior myocardial infarction? Insights from the

heart failure; N Engl J Med. October 2010;363(15):(1419-28).

APEX-AMI Trial (Accompanied by an editorial). Am Heart J. 2010;160(4):671-677.

Heart Failure Society of America, Lindenfeld J, Albert

Stebbins A, Mehta RH, Armstrong PW, Lee KL, Hamm C, Van

NM, Boehmer JP, Collins SP, Ezekowitz JA, Givertz MM,

de Werf F, James S, Toftegaard-Nielsen T, Seabra-Gomes

Katz SD, Klapholz M, Moser DK, Rogers JG, Starling RC,

R, White HD, Granger CB for the APEX AMI Investigators.

Stevenson WG, Tang WH, Teerlink JR, Walsh MN; HFSA 2010

A model for predicting mortality in acute ST-segment

Comprehensive Heart Failure Practice Guidelines. J Card.

elevation myocardial infarction treated with primary

Fail. June 2010;16(6):(e1-194).

percutaneous coronary intervention: Results from the Assessment of Pexelizumab in Acute Myocardial Infarction

Oreopoulos A, Ezekowitz JA, McAlister FA, Kalantar-Zadeh K,

Trial. Circ Cardiovasc Interv. 2010;3:414-422.

Fonarow GC, Norris CM, Johnson JA, Padwal RS; Association between direct measures of body composition and prognostic factors in chronic heart failure. Mayo Clin Proc. July 2010;85(7):(609-17). Howlett JG, McKelvie RS, Costigan J, Ducharme A, EstrellaHolder E, Ezekowitz JA, Giannetti N, Haddad H, Heckman GA, Herd AM, Isaac D, Kouz S, Leblanc K, Liu P, Mann E, Moe GW, O'Meara E, Rajda M, Siu S, Stolee P, Swiggum E, Zeiroth S; Canadian Cardiovascular Society. The 2010 Canadian Cardiovascular Society guidelines for the diagnosis and management of heart failure update: Heart failure in ethnic minority populations, heart failure and pregnancy, disease management, and quality improvement/assurance

Bueno H, Armstrong PW, Buxton MJ, Danchin N, Lubsen J,

programs. Can J Cardiol. 2010 Apr;26(4):185-202.

Roland E, Verheugt FW, Zalewski A, Jackson N, Komajda M, Steg PG. The future of clinical trials in secondary

Oreopoulos A, Padwal R, McAlister FA, Ezekowitz J, Sharma

prevention after acute coronary syndromes. (Eur Heart J. –

AM, Kalantar-Zadeh K, Fonarow GC, Norris CM. Association

doi:10.1093/eurheartj/ehq388)

between obesity and health-related quality of life in patients with coronary artery disease. Int J Obes (Lond).

Armstrong PW. Aldosterone antagonists – last man

2010 Apr 13.

standing? (Editorial) New Engl J Med. 2011;364(1):79-80. Ezekowitz JA, Kaul P. The epidemiology and management Armstrong PW, Welsh RC. (Editorial) Rear-view mirror

of elderly patients with myocardial infarction or heart

observations on bleeding in acute coronary syndromes. J.

failure. Heart Fail Rev. 2010 Mar 8.

Am. Coll. Cardiol. Intv. 2010;3(11):1178-1180. Weatherley BD, Cotter G, Dittrich HC, DeLucca P, Mansoor Mehta RH, O’Shea JC, Stebbins AL, Granger CB, Armstrong

Canadian VIGOUR Centre — Two-thousand and Ten — Annual Report

GA, Bloomﬁeld DM, Ponikowski P, O'Connor CM, Metra M,

Publications—2010

Massie BM; PROTECT Steering Committee, Investigators, and

Tjandrawidjaja MC, Fu Y, Westerhout CM, Wagner GS,

Coordinators. Design and rationale of the PROTECT study:

Granger CB, Armstrong PW. QRS score at hospital discharge

a placebo-controlled randomized study of the selective

is a strong prognostic marker in patients with ST segment

A1 adenosine receptor antagonist rolofylline for patients

elevation myocardial infarction undergoing primary

hospitalized with acute decompensated heart failure and

percutaneous coronary intervention. JACC. 2010;55(10)

volume overload to assess treatment effect on congestion

(Suppl A):A125.

and renal function. J Card Fail. 2010 Jan;16(1):25-35. Epub 2009 Dec 11. Ezekowitz JA. A new pathway? Failure, fragility and fractures. (Editorial) Eur Heart J. 2010 Jan;31(1):9-11. Welsh RC, Cockﬁeld SM, Campbell P, Hervas-Malo M, Gyenes G, Dzavik V. Cardiovascular Assessment of Diabetic EndStage Renal Disease Patients Before Renal Transplantation.

“I had the privilege to work with Dr. Armstrong and the VIGOUR group over the past year. It has been an invaluable time of learning, ﬁlled

Transplantation. 2010 Nov 2. [Epub ahead of print]

with enthusiasm and support by

Sonnenberg B, Rutledge J, Welsh RC. Occlusion of a large

all the members of the VIGOUR

expanding saphenous vein bypass graft aneurysm with percutaneously injected ethylene-vinyl alcohol copolymer.

JACC Cardiovasc Interv. 2010 Oct;3(10):1089-90. Elbarouni B, Elmanfud O, Yan RT, Fox KA, Kornder JM, Rose B, Spencer FA, Welsh RC, Wong GC, Goodman SG, Yan AT. Temporal trend of in-hospital major bleeding among patients with non ST-elevation acute coronary syndromes.

Am Heart J. 2010 Sep;160(3):420-7.

team. Clinical research could be a challenging and even intimidating experience for the beginner, I was fully supported and intellectually encouraged by Dr. Armstrong and

Leonardi S, Rao SV, Harrington RA, Bhatt DL, Gibson CM, Roe MT, Kochman J, Huber K, Zeymer U, Madan M, Gretler DD, McClure MW, Paynter GE, Thompson V, Welsh RC. Rationale and design of the randomized, double-blind trial testing INtraveNous and Oral administration of elinogrel, a selective and reversible P2Y(12)-receptor inhibitor, versus clopidogrel to eVAluate Tolerability and Efﬁcacy in nonurgent Percutaneous Coronary Interventions patients

Cindy Westerhout, which made my ﬁrst taste of cardiovascular research exciting and very stimulating. The VIGOUR center is an excellent

(INNOVATE-PCI). Am Heart J. 2010 Jul;160(1):65-72.

media for planting the seeds of

Lee TC, Goodman SG, Yan RT, Grondin FR, Welsh RC, Rose

future researchers; the educational,

B, Gyenes G, Zimmerman RH, Brossoit R, Saposnik G, Graham JJ, Yan AT; Canadian Acute Coronary Syndromes I and II, Canadian Global Registry of Acute Coronary Events (GRACE/GRACE2) and the Canadian Registry of Acute Coronary Events (CANRACE) Investigators. Disparities in management patterns and outcomes of patients with nonST-elevation acute coronary syndrome with and without a history of cerebrovascular disease. Am J Cardiol. 2010 Apr 15;105(8):1083-9.

Selected Presentations by our Trainees

professional and interpersonal atmosphere is the ultimate necessity for the motivation of trainees to continue on their research efforts and complete great projects.“

Alhadramy O, Westerhout CM, Brener SJ, Granger CB,

—Olga Toleva, MD

Armstrong PW. Is visual interpretation of coronary

Cardiology trainee

epicardial ﬂow reliable in ST elevation myocardial infarction patients undergoing primary angioplasty? Insights from APEX-AMI. JACC. 2010;55(10)(Suppl A):A112

Annual Report — Two-thousand and Ten — Canadian VIGOUR Centre

Appendix 1: The Canadian Cardiac Chronicle Newsletters

Appendix 1 The Canadian Cardiac Chronicle Newsletters

Annual Report — Two-thousand and Ten — Canadian VIGOUR Centre

Appendix 1: The Canadian Cardiac Chronicle Newsletters

Canadian VIGOUR Centre — Two-thousand and Ten — Annual Report

Appendix 1: The Canadian Cardiac Chronicle Newsletters

Annual Report — Two-thousand and Ten — Canadian VIGOUR Centre

Appendix 1: The Canadian Cardiac Chronicle Newsletters

Canadian VIGOUR Centre — Two-thousand and Ten — Annual Report

Appendix 2: Beyond 2000 Program

Appendix 2 Beyond 2000 Program

Annual Report — Two-thousand and Ten — Canadian VIGOUR Centre

Appendix 2: Beyond 2000 Program

New Concepts in Acute Coronary Syndromes: Beyond 2000 (XVI) Nouveaux principes sur le syndrome coronarien aigu : Au-delà de l’an 2000 (XVI) Held in association with the Canadian Cardiovascular Congress 2010 Tenu en collaboration avec le Congrès canadien sur la santé cardiovasculaire 2010

Sunday, October 24, 2010 • Le dimanche 24 octobre 2010 07:55–12:00 • de 7 h 55 à 12 h Room 517 D • Salle 517 D Palais des congrès de Montréal Montreal, Quebec • Montréal (Québec) This event is an accredited group learning activity under Section 1 as defined by the Royal College of Physicians and Surgeons of Canada for the Maintenance of Certification program. It is approved by the Canadian Cardiovascular Society for a maximum of 4 credits. New Concepts in Acute Coronary Syndromes: Beyond 2000 (XVI) was co-developed with the Canadian Cardiovascular Society, the University of Alberta, Merck, and sanofi-aventis Canada and Bristol-Myers Squibb Canada, and was planned to ensure the evidence presented is valid, objective and balanced.

L’événement suivant fait partie des activités de DPC collectives en vertu de la Section 1, telles qu’approuvées par le Collège royal des médecins et chirurgiens du Canada pour le programme de Maintien du certificat. Il a été approuvé par la Société canadienne de cardiologie pour un maximum de 4 crédits. Nouveaux principes sur le syndrome coronarien aigu : Au-delà de l’an 2000 (XVI) a été élaboré en collaboration par la Société canadienne de cardiologie, l’Université de l’Alberta, Merck, et sanofi-aventis Canada et Bristol-Myers Squibb Canada; il a été conçu d’une manière qui assure la validité, l’objectivité et l’équilibre des faits présentés.

Canadian VIGOUR Centre — Two-thousand and Ten — Annual Report

Appendix 2: Beyond 2000 Program

New Concepts in Acute Coronary Syndromes: Beyond 2000 (XVI) Nouveaux concepts dans les syndromes coronariens aigus : Au-delà de l’an 2000 (XVI) 07:55

Welcoming Remarks Mot de bienvenue

Paul Armstrong, MD University of Alberta, Edmonton, Alberta