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2009 Annual Report - Centre of Cardiovascular Research and

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									Centre of Cardiovascular
Research and Education
in Therapeutics
Annual Report


        Director’s report              .    .    .    .    .    .    .    .    .    .    .    .    .    . 1
        Mission statement  .                .    .    .    .    .    .    .    .    .    .    .    .    . 2
        Scientific Advisory Board                     .    .    .    .    .    .    .    .    .    .    . 3
        Operational review .                .    .    .    .    .    .    .    .    .    .    .    .    . 8
        Caulfield Clinical Trial Centre                    .    .    .    .    .    .    .    .    .   16
        Research training and education  .                           .    .    .    .    .    .    .   24
          Meetings and symposia                                                                        26
        Grants          .    .    .    .    .    .    .    .    .    .    .    .    .    .    .    .   28
        Publications  .           .    .    .    .    .    .    .    .    .    .    .    .    .    .   30
        Contact  .           .    .    .    .    .    .    .    .    .    .    .    .    .    .    .   38

| Annual Report 2009
Director’s report

                                                 It gives me great pleasure to present this
                                                 year’s CCRE Therapeutics Annual Report
                                                 2009 was the first year of CCRET being
                                                 a stand-alone Monash-approved research
                                                 centre This evolved from CCRET’s previous
                                                 incarnation as an NHMRC Centre of Clinical
                                                 Research Excellence

                                                 Based on all metrics, CCRE Therapeutics
                                                 is now a well-established, growing and
                                                 self-sufficient stand-alone centre Indeed,
                                                 2009 was CCRET’s most productive year
                                                 ever, academically This is reflected by the
                                                 large body of research work published,
                                                 presentations given at local, national and
                                                 international meetings as well as teaching
                                                 load and student supervision

Highlights of 2009 include:
•   SCREEN-HF: This study has been presented at both the 2009 CSANZ and European Society of Cardiology
    meetings following successful recruitment of more than 4000 patients in the cross-sectional cohort study

    Leveraging off this initial cohort we have been successful in obtaining further funding for this study Our close
    collaborator on SCREEN-HF, Associate Professor Jock Campbell of the St Vincent’s Research Institute, received an
    NHMRC Project Grant for longitudinal follow up of the 4000 patients in the initial cohort This will allow us to observe
    the potential for development of LV dysfunction over time as well as which patients are at greatest risk of this
    We were also successful in obtaining National Heart Foundation funding support for a drug intervention study
    in the highest of these high risk subjects to prevent the development of these cardiac abnormalities Furthermore,
    we have received additional funding from MBF for sequential NT-proBNP testing Therefore, SCREEN-HF has
    become a large and internationally important flagship project for CCRE Therapeutics

•   INTEGRATE: The Integrate study of physician inertia has been successfully completed involving participation by
    both general practitioners and their patients Almost 8000 patients were recruited by Australian GPs into this study
    The final phase of data collection was completed in late 2009 utilising CCRE Therapeutics web-enabled data
    capture technology

•   CHAT: The CHAT study has been completed and analysed Results were presented for the first time
    in a late-breaking session of the European Heart Failure Association meeting in Nice, France in June 2009

•   ASPREE: Following a joint submission by the ASPREE researchers (led by Professor John McNeil) and colleagues
    from the USA (led by Professor Richard Grim) this large-scale double-blind randomised placebo-controlled trial of
    low dose aspirin for primary prevention of disease has received a USD$50 million grant from the National Institute
    of Health This funding will enable recruitment to commence early next year of the 19,500 participants involved

•   ATMOSPHERE: This global study of the effects of aliskiren in patients with systolic chronic heart failure aims to recruit
    more than 7000 participants I have been appointed Chairman of the Steering Committee of the study, which is also
    being conducted locally at The Alfred hospital

                                                                   Centre of Cardiovascular Research and Education in Therapeutics | 1
        Highlights of 2009 continued
        •   RENAL DENERVATION: CCRE Therapeutics led this pivotal and highly successful first-in-man study to evaluate
            this novel strategy in the treatment of refractory hypertension I presented these results at a late-breaking clinical
            trial session of the American College of Cardiology in March 2009 and the study results were simultaneously published
            in the Lancet Following the success of this proof-of-concept study, work continues with further clinical trials

        •   STABILITY: This international trial of an investigational drug, darapladip, in patients with chronic coronary
            heart disease receiving standard practice care is being undertaken at our Clinical Trial Centre at Caulfield
            CCRET achieved second highest recruitment Australia-wide Patients will be followed every six months
            for approximately three-and-a-half years

        •   MEDICAL EDUCATION, eg CSANZ symposia: CCRE Therapeutics continues its commitment to medical education
            programs and once again held two highly successful symposia at this year’s CSANZ meeting, with further events
            scheduled for 2010

        In summary, 2009 was another successful year at CCRE Therapeutics
        Based on local and international feedback the CCRE Therapeutics
        ‘brand’ is increasingly well recognised 2010 promises to be an even
        more exciting year for the Centre

        Henry Krum, MBBS, PhD, FRACP, FCSANZ
        Professor of Medicine

        Mission statement
        To improve clinical outcomes at the individual
        and community level through the use of evidence,
        based on high-quality clinical research

2 | Annual Report 2009
Scientific Advisory Board

            Professor Henry Krum
            MBBS, PhD, FRACP, FCSANZ

            Professor Henry Krum completed his MBBS at the University of Melbourne
            in 1981, became a Fellow of the Royal Australasian College of Physicians
            in 1989 and completed a PhD at the University of Melbourne in 1991.

            Professor Krum is a Consultant Physician based at the Heart Centre,
            The Alfred hospital, and a specialist in heart failure management. Professor Krum’s
            grant achievements include awarding of a five-year NHMRC Program Grant for
            2005 to 2009 in heart failure research which has recently been reviewed
            for 2010 to 2014. He is the author of over 280 peer-reviewed manuscripts,
            16 book chapters and is co-author of a text book of heart failure therapeutics.
            He has been Principal Investigator, Executive Committee member and
            Data Safety Monitoring Board Chairman for numerous international trials
            in cardiovascular therapeutics.

            Associate Director
            Associate Professor Christopher Reid
            BA, DipEd, MSc, CertHealthEcon, PhD

            Chris graduated from the University of Queensland in 1980 before undertaking
            graduate studies in Exercise Physiology at West Virginia University and a PhD
            in this department.

            Previously, Chris was Head of the Cardiovascular Disease Prevention Unit at
            the then Baker Heart Research Institute (now Baker-IDI) and has held roles as
            the Director of the 2nd Australian National Blood Pressure Study and Program
            Director of the Australian Society of Cardiothoracic Surgeons Victorian database.
            Over the past ten years, his work has led to the development of a series of
            clinical tools for general practitioners to assist in the uptake of evidence-based
            management of both primary and secondary prevention of cardiovascular
            disease. He has been invited to give eight international and 26 national lectures
            and has participated as a WHO consultant for prevention of cardiovascular
            disease in both Mongolia and Vietnam.

                                    Centre of Cardiovascular Research and Education in Therapeutics | 3
        Professor John McNeil

        Professor John McNeil has been Chair, Monash University Department
        of Epidemiology and Preventive Medicine at The Alfred hospital, Melbourne,
        since 1986.

        He graduated in medicine from the University of Adelaide, subsequently
        completing a PhD in Clinical Pharmacology at the University of Melbourne
        and a Master of Science degree in epidemiology at the University of London.
        He completed specialty training as a physician and subsequently held senior
        medical staff positions at the Austin, Repatriation, The Alfred and Monash
        Medical Centres in Victoria. His research interests focus on drug safety.

        He is Scientific Secretary of the International Society of Cardiovascular
        Pharmacotherapy and a member of the Editorial Board of ‘Cardiovascular
        Drugs and Therapeutics’. He is a Fellow of Food Standards Australia and
        New Zealand and chairs the Ethics Committee at The Alfred hospital.
        He is also currently a member of the Colonial Foundation Board.

        During his career he has been a member of a wide range of national scientific
        advisory committees established by the National Health and Medical Research
        Council, the Commonwealth Departments of Health, Aging and Veteran’s
        Affairs, the Royal Australasian College of Physicians, the National Heart
        Foundation, the National Stroke Foundation and Food Standards Australia.

        He has published over 300 scientific papers and in 2008, was made a member
        of the Order of Australia in recognition of his contribution to Public Health.

        Professor Andrew Tonkin
        MBBS, FRACP

        Professor Andrew Tonkin is Head of the Cardiovascular Research Unit in
        the Department of Epidemiology and Preventive Medicine, Monash University.

        He is also a Consultant Cardiologist at Austin Health. He has also been
        Chief Medical Officer with the National Heart Foundation of Australia.

        Professor Tonkin is past Chairman of the Australian Expert Advisory Group
        on Heart, Stroke and Vascular Diseases, which advised Government, and is
        a member of the Executive Board of the Council on Clinical Cardiology of the
        World Heart Federation.

4 | Annual Report 2009
Professor Paul Myles

Professor Paul Myles is the Director of Anaesthesia and Perioperative Medicine
at the Alfred Hospital, and Professor of Anaesthesia at Monash University.
Professor Myles is involved in a number of large multi-centre trials aiming to
improve outcomes after surgery and anaesthesia. These include an investigation
of nitrous oxide in anaesthesia (the ENIGMA Trial), and aspirin with or without
tranexamic acid in coronary artery surgery (the ATACAS Trial).

Professor Jamie Cooper

Professor Cooper has been Head of Trauma Intensive Care and a senior
Intensivist at the Alfred Hospital since 1991. For most of this time he has been
Associate Director, or more recently Deputy Director of ICU, and has acted as
the Director of this large Department on many occasions. Through published
research and involvement with Department of Human Service (DHS)
committees concerning trauma and intensive care, he supported and
highlighted the need for and the introduction of the current Victorian Trauma
System. He Chairs the DHS Trauma Quality Committee which monitors and
provides expert interpretation for the impact of the Trauma System on trauma
outcomes in Victoria. In 2004, he was appointed Associate Director (Clinical
Research) of the National Trauma Research Institute, having responsibility for
coordinating all clinical research relating to Trauma at the Alfred (all specialities
including Intensive Care).

Professor Andrew Forbes
BSc(Hons), MSc, PhD

Professor Forbes provides biostatistical expertise and professional leadership
to CCRE Therapeutics. He worked in the pharmaceutical industry in the US,
before joining Monash University to head one of the largest biostatistical units
in Victoria, in the Department of Epidemiology and Preventive Medicine.

                         Centre of Cardiovascular Research and Education in Therapeutics | 5
        Director                               Research assistants
        Professor Henry Krum                   Venu Ariyaratne
                                               Molly Bond
                                               Daniella Brasacchio
        Associate Director                     Harriet Carruthers
                                               Vibhasha Chand
        Associate Professor Christopher Reid   Fiona Collier
                                               Lisa Curran
                                               Kristina Di Giambattista
        Research Fellows                       Kate Evans
                                               Amy Finlay
        Dr Nick Adrianopolous                  Alison Foster
        Ms Angela Brennan                      Molla Huq
        Mr Carl Costolloe                      Philippa Loane
        Dr Linda De Melis                      Jessica Lockery
        Dr Diem Dinh                           Fanny Sampurno
        Dr Andrea Driscoll                     Caroline Steer
        Dr Ruth Hannan                         Francesca Stewart
        Dr Alice Owen                          Trieu-Anh Thi Truong
        Dr Emily Parker                        Lavanya Vijayasingham
        Dr Kathlyn Ronaldson
        Ms Louise Shiel
        Mr John Varigos                        PhD students
        Dr Bing Wang
        Dr Katrina Watson                      Ms Zanfina Ademi
        Dr Robyn Woods                         Ms Jessica Chellappah
                                               Dr Maros Elsik
                                               Mr Steven Haas
        Software developers                    Dr Pupalan Iyngkaran
                                               Dr William Kemp
        Waranon Buranasiri                     Dr Dipak Kotecha
        Miteshkumar Chaudhari                  Dr Suree Lekawanjivit
        Andrew Hannaford                       Dr Michele McGrady
        Mahfuzal Haque                         Ms Lavinia Tran
        Nino Hay                               Dr Hendrik Zimmet
        Ramya Jaganathan                       Ms Ella Zomer
        Kunnapoj Pruksawongsin
        Phillip Scotney
        Douglas Wong                           General administration
        Igor Yeykelis
                                               Callum Brennan
                                               Laura Ellis
        Nursing                                Jo Harwood
                                               Anne Jenes
        Anne Bruce                             Sarah Mann
        Michelle Hooy                          Thomas Mann
        Kimberly Irwin                         Simon Montgomery
        Elizabeth Jenkins                      Ajitha Paldano
        Susan Loftis
        Jessica Maggs
        Sue Montgomery
        Christine Mulvany
        Christine Poole
        Louise Turnour
        Kathleen White

6 | Annual Report 2009
International collaborating academics
Professor Barry Massie, MD, FACC                             Professor Salim Yusuf, MD (Bangalore), DPhil (Oxford), MRCP
Professor of Medicine and Chief, Cardiology Division         McMaster University
San Francisco VAMC at University of California               Faculty of Health Sciences
San Francisco, USA                                           Hamilton Health Sciences Corporation
                                                             General Site, McMaster Clinic
Professor Marcus Flather, BSc, MBBS, FRCP                    237 Barton St. E.
Director                                                     Hamilton, Ontario, Canada
Clinical Trials and Evaluation Unit
Royal Brompton Hospital                                      Professor Stefan Blankenberg, MD
London, UK                                                   Department of Medicine II
                                                             Johannes Gutenberg-University
Professor Frank Ruschitzka, MD                               Mainz, Germany
Assistant Professor of Medicine
Department of Cardiology                                     Professor Richard Grimm, MD, PhD
University of Zurich                                         Director
Zurich, Switzerland                                          Berman Center for Outcomes and Clinical Research
                                                             Minneapolis Medical Research Foundation
Professor William T Abraham, MD, FACP, FACC, FAHA            Minneapolis, MN, USA
Division of Cardiovascular Medicine                          Dr Anne Murray, MD
Deputy Director                                              HFA Senior Care Clinic
Davis Heart and Lung Research Institute                      1425 10th Avenue South
The Ohio State University, USA                               Minneapolis, MN 55404

Professor P Gabriel Steg                                     Dr Paul Sobotka, MD
Professor of Cardiology                                      Department of Cardiology
Université Paris-VII                                         Hennepin County Medical Center
Director of Coronary Care Unit                               Minneapolis, MN, USA
Hôpital Bichat
Paris, France

Dr Deepak Bhatt, MD, FACC, FAHA
Chief of Cardiology, VA Boston Healthcare System
Director, Integrated Interventional Cardiovascular Program
at Brigham and Women’s Hospital and the VA Boston
Healthcare System

The CCRE Therapeutics group

                                                               Centre of Cardiovascular Research and Education in Therapeutics | 7
        Operational review

        CCRE Therapeutics can divide its core strengths into
        three main areas: clinical trials, clinical informatics and
        pharmacoepidemiology/translational research.
        Clinical Trials                                               systolic and diastolic blood pressure following the
                                                                      procedure. In addition, there was evidence of reduced
                                                                      renal sympathetic activity. Collaborators were Baker
        Our clinical trials activities are conducted at the           Heart Institute and St Vincent’s Hospital, Melbourne.
        Clinical Pharmacology department at the Alfred                This exciting work now proceeds to the randomised
        Hospital and also at the Clinical Trial Centre at             clinical trial stage.
        Caulfield Hospital. Our clinical trials focus on
        mechanistic and hospital-based studies,                       Publications
        a number of which are outlined in the next section.           Schlaich MP, Sobotka PA, Krum H, Whitbourn R,
                                                                      Walton A, Esler MD. Renal Denervation as a Therapeutic
        Renal denervation                                             Approach for Hypertension: Novel Implications for an
        CCRE led the pivotal first-in-man study to evaluate this      Old Concept. Hypertension, 2009 Dec;54(6):1195–1201.
        novel strategy in the treatment of refractory hypertension.
                                                                      Schlaich MP, Sobotka PA, Krum H, Lambert E, Esler MD.
        Renal denervation involves a catheter-based approach          Renal sympathetic-nerve ablation for uncontrolled
        via femoral access to knock out the sympathetic nerves        hypertension. N Engl J Med. 2009 Aug 27;
        that run adjacent to the renal artery. This percutaneous      361(9):932–4. (letter)
        approach is minimally invasive and the procedure takes
        about 40 minutes. First-in-man results were presented         Krum H, Schlaich M, Whitbourn R, Sobotka PA,
        by Henry Krum at a late-breaking clinical trial session       Sadowski J, Bartus K, Kapelak B,Walton A, Sievert H,
        of the American College of Cardiology meeting in              Thambar S, Abraham WT, Esler M. Catheter-based
        March 2009 and simultaneously published in the Lancet.        renal sympathetic denervation for resistant hypertension:
        The key findings were those of peri-procedural and            a multicentre safety and proof-of-principle cohort study.
        long-term safety as well as marked reduction in both          Lancet 2009; 373:1275–1281.

8 | Annual Report 2009
Aliskiren Trial to Minimize OutcomeS in                         particular effects on the ventricular remodelling process.
Patients with HEart failuRE (ATMOSPHERE)                        The primary efficacy parameter of UNIVERSE was change
Henry Krum has been appointed as Study Chair of the             in left ventricular ejection fraction (LVEF) from baseline to
ATMOSPHERE study which is being conducted at the                26 weeks post randomisation in response to placebo or
Alfred Hospital and approximately 800 other sites               high-dose rosuvastatin (40mg/day).
throughout the world. The aim is to recruit more than
7000 patients with systolic chronic heart failure to test the   Other parameters measured included echocardiogram,
question of whether direct renin inhibition with the agent,     high sensitive C-reactive protein and tumour necrosis
aliskiren, is useful as add-on therapy to the gold standard     factor alpha. However, despite previous data indicating
agent (ACE-inhibitors) or may even be used as an                beneficial effect of statins on CHF, and a large reduction
alternative to these agents.                                    in plasma lipids achieved, this study did not observe
                                                                a rosuvastatin-induced improvement in LVEF or indeed
Chronic Heart failure Assisted                                  most other imaging or blood parameters in comparison
by Telephone study (CHAT)                                       to placebo. We therefore conducted a substudy to explore
The CHAT study was a randomised control trial of                mechanistic reasons why beneficial remodelling effects
telephone support for chronic heart failure patients at         were not observed in this study.
high risk of rehospitalisation. This project was funded
by the NHMRC, Heart Foundation of Australia and the             Blood samples were collected from UNIVERSE patients
Medical Benefits Fund.                                          at baseline and after 26 weeks of treatment, and stored
                                                                for analysis of serum coenzyme Q10, PINP and PIIINP
This project implemented the first Australia-wide trial of      analysis. CoQ levels were significantly reduced after
telephone support for CHF patients. The aims of the study       26 weeks of rosuvastatin statin therapy, compared to
were to determine whether automated telephone support           placebo in CHF patients in UNIVERSE trial. Patients with
will improve quality of life and reduce death and hospital      CHF matched for age, gender and severity of disease who
admission for rural and remote CHF patients and to test         had been taking statins for 12 months or longer had CoQ
this system of care as an exemplar of a novel chronic           levels significantly lower than UNIVERSE patients at
disease management strategy in areas remote from                baseline (p=0.0001). Serum type I and III N-terminal
access to multi-disciplinary care.                              procollagen peptide (PINP and PIIINP), measures of
                                                                collagen turnover which can contribute to cardiac fibrosis
The automated telephone support comprised of an                 were significantly increased in the rosuvastatin group
interactive telecommunication software tool (Telewatch)         compared to baseline in UNIVERSE patients (PINP:
with follow up by trained cardiac nurses. Patients with         p=0.03, PIIINP: p=0.001). These data are now
a General Practice (GP) diagnosis of heart failure were         published in Int. J. Cardiol.
randomised to telephone support (217 patients) or usual
care (188 patients) using a cluster design involving            Publications
136 GPs throughout Australia. Results showed that               Ashton E, Windebank E, Skiba M, Reid C, Schneider H,
automated telephone support to the rural and remote             Rosenfeldt F, Tonkin A, Krum H. Why did high-dose
heart failure patients resulted in a 30 per cent reduction      rosuvastatin not improve cardiac remodelling in chronic
in risk of all-cause death and hospitalisation. The CHAT        heart failure? Mechanistic insights from the UNIVERSE
study explored a novel system of healthcare delivery,           study. Int J Cardiol, 2009 (in press).
targeting rural and remote Australians with chronic
disease. Automated telephone support may become                 ATACAS Trial
a useful tool to address access issues for management           Cardiac surgery activates platelets and coagulation
programs in chronic disease patients.                           factors, and the fibrinolytic pathway. Excessive bleeding
                                                                is common. This may require surgical re-exploration and
Results were presented in a late breaking trials session        increases morbidity and mortality. Recent aspirin exposure
at the European Heart Failure Association meeting               increases surgical bleeding, and so it is routine practice in
in Nice, France.                                                most cardiac surgical centres for aspirin to be ceased one
                                                                week before elective cardiac surgery. But a recent study
UNIVERSE: Coenzyme Q10                                          found that aspirin had a lower mortality, as well as less
and Collagen Substudy                                           stroke, renal failure and bowel infarction (all P<0.01).
The rosUvastatiN Impact on VEntricular Remodelling              Another drug, tranexamic acid (TxA), is sometimes used to
cytokineS and neurohormonEs (UNIVERSE) Study was                reduce bleeding after cardiac surgery. It works by blocking
established to address the deficit in prospective clinical      fibrinolysis (‘clot breakdown’) during and after surgery.
trial data regarding the use of statins in CHF and in           It can block the bleeding risk associate with aspirin,

                                                                  Centre of Cardiovascular Research and Education in Therapeutics | 9
        and does not increase thrombotic risk. Meta-analyses            The study design and rationale underwent peer review
        of trials have shown that antifibrinolytic therapy reduces      and was published in the American Heart Journal
        blood loss, need for blood transfusion and re-operation         (March 2009). This NHMRC-funded clinical trial involves
        for bleeding in cardiac surgery.                                7000 patients to provide a definitive evaluation of the
                                                                        safety of nitrous oxide anaesthesia. The primary endpoint
        This large, multi-centre, randomised, double-blind,             is a composite of death and serious cardiovascular events
        factorial trial in 4600 cardiac surgical patients is looking    within 30 days of surgery. To date we have enrolled over
        for a reduction in major complications or death with aspirin    2600 patients in 30 centres throughout the world
        and/or TxA. We have established a trial network of at least     (see: www.enigma2.org.au).
        15 hospitals, with support from cardiac surgeons and
        anaesthetists from Australia, Canada and UK.                    Publications
        Patient enrolment has commenced, with more                      Myles PS, Leslie K, Peyton P, Paech M, Forbes A,
        than 780 patients to date (see: www.atacas.org.au).             Chan MT, Sessler D, Devereaux PJ, Silbert BS,
                                                                        Jamrozik K, Beattie S, Badner N, Tomlinson J, Wallace S.
        The study design and rationale underwent peer review and        Nitrous oxide and perioperative cardiac morbidity
        was published in the American Heart Journal (Feb 2008).         (ENIGMA-II) Trial: rationale and design. ANZCA Trials
        We have also done a systematic review and meta-analysis         Group. Am Heart J. 2009 Mar;157(3):488–494.e1.
        investigating the effects of antifibrinolytic therapy in
        cardiac surgical patients treated with aspirin                  Prevalence of ICD and/or CRT device therapy
        (Br J Anaesth, February 2009).                                  in patients admitted to hospital with
                                                                        decompensated heart failure
        Publications                                                    Heart failure is associated with high hospitalisation and
        McIlroy DR, Myles PS, Phillips LE, Smith JA.                    mortality rates. Over the years there have been many
        Antifibrinolytics in cardiac surgical patients receiving        randomised controlled trials that have shown the benefits
        aspirin: a systematic review and meta-analysis.                 of heart failure treatment strategies and have focussed
        Br J Anaesth. 2009 Feb;102(2):168–78.                           on the uptake and optimisation of pharmacotherapy.
                                                                        However there have been few studies that have
        ENIGMA-II Trial                                                 investigated the uptake of these devices.
        More than 2.5 million anaesthetics are given each year
        in Australia (1:10 Australians), with the majority receiving    The aim of this study was to determine the proportion of
        nitrous oxide. Approximately 25 per cent of patients            patients with heart failure that met the criteria for cardiac
        undergoing major surgery have known coronary artery             resynchronisation therapy (CRT) device implantation
        disease (CAD) or risk factors for CAD. In 1990, approximately   according to National Heart Foundation (NHF) guidelines,
        one million of the 25 million Americans who underwent           and to evaluate the prevalence of device therapy use in
        non-cardiac surgery suffered a perioperative cardiac event,     these patients. This study was funded by Medtronic.
        resulting in $20 billion in costs.
                                                                        This study was a retrospective review of 1274 medical
        Nitrous oxide interferes with vitamin B12 and folate            records of patients discharged from hospital during 2007
        metabolism. This impairs production of methionine               with a primary discharge diagnosis of heart failure.
        (from homocysteine), used to form tetrahydrofolate              The study involved six hospitals throughout Australia
        and thymidine during DNA synthesis. It has been                 which included four metropolitan, one rural and one
        repeatedly demonstrated that nitrous oxide anaesthesia          private hospital. Of the medical records that were
        increases postoperative homocysteine levels. Chronic            searched less than half (n=570) had a primary discharge
        hyperhomocysteinaemia is associated with cardiovascular         diagnosis of heart failure. We found that 23 per cent
        disease, and acute hyperhomocysteinaemia is known               (128/570) of patients had a device implanted. Only 1 per cent
        to cause endothelial dysfunction. One small trial has           (4/29) of patients with no device met the NHF guideline
        demonstrated an increased incidence of postoperative            criteria for CRT implantation. The mortality rate in patients
        myocardial ischaemia in patients receiving nitrous oxide        with a CRT device was lower than patients with no device.
        anaesthesia. Reducing postoperative myocardial infarction
        and death are important aims for those with CAD                 In conclusion, outcomes in this population remain poor
        undergoing major surgery.                                       with 60 per cent being readmitted and nearly a quarter
                                                                        of patients not surviving after 18 months post-discharge.
                                                                        Due to missing information in the medical record,
                                                                        there was insufficient data to conclude that guideline
                                                                        recommendations were adhered to.

10 | Annual Report 2009
INTERSTROKE                                                        Now that the Pilot Phase has been completed, there will
Stroke is a major global health problem, yet few studies           be a transition into the main study with up to 10 centres
have examined the risk factors for stroke and its subtypes         participating in Australia. INTERSTROKE will provide
in different ethnic populations representing different             essential information on conventional and emerging risk
regions of the world. Compared to coronary heart disease,          factors to help guide population health initiatives aimed
traditional risk factors (eg hypertension, hypercholesterolemia)   at preventing stroke in low and high income countries.
appear to exert different magnitudes of risk for stroke and        To be successful, INTERSTROKE will involve national
within stroke subtypes. Any effective global strategy to           and international collaboration. John Varigos, from CCRE
reduce the risk of stroke mandates a systematic and                Therapeutics, is the national coordinator and, together
standardised study of the contribution of traditional and          with Graeme Hankey from the Royal Perth Hospital, will
emerging risk factors within defined ethnic groups and             coordinate the Australian arm of the study. INTERSTROKE
geographical locations for each of the stroke subtypes.            will have enormous implications for our understanding of
In order to provide reliable answers, these studies need           the causes of stroke within Australia and around the world.
to be very large, so as to include large numbers of cases
of strokes of each subtype.
                                                                   Clinical Informatics and
INTERSTROKE has been designed to achieve this by
utilising a global research network of investigators centrally     Data Management
coordinated through the Public Health Research Institute
in Hamilton, Ontario, Canada. Many members of this                 The Clinical Informatics and Data Management Unit
research network completed a similar study in 2005                 (CIDMU) provides key platform technologies for the
for myocardial infarction (MI) called INTERHEART.                  conduct of epidemiological, clinical trial and health
INTERHEART included 30,000 participants from                       services research. The platform technologies include;
52 countries and showed that nine modifiable risk
factors accounted for over 90 per cent of the risk.                •     multi-centre clinical trials and registry
                                                                         data management;
A similar study is necessary in stroke because:                    •     web-based, e-CRF, fax and paper-based
                                                                         data capture facilities;
1. the causes of stroke are far more diverse than MI;              •     web-based or telephone-based
2. many of the common risk factors for stroke and MI                     randomisation services;
   (eg lipids) appear to exert very different magnitudes           •     trial and site management capabilities;
   of risk for stroke compared with MI; and                        •     trial and site monitoring capabilities; and
3. there are limited epidemiological studies in stroke.            •     statistical data analysis and study design capabilities.

This study compares risk factors in people with stroke             The platform technologies have been developed in
(cases) to people without stroke (controls) in a large,            accordance with international regulatory and national
international case control study that includes approximately       privacy and ethical guidelines. The following projects
24,000 cases and controls from about 37 countries.                 are being managed and conducted by CIDMU.
Countries will recruit the following ethnic groups:
Caucasians, Chinese, South Asians, Africans and                    Melbourne Interventional Group (MIG)
native South Americans.                                            The Melbourne Interventional Group (MIG) remains the
                                                                   only Percutaneous Coronary Intervention (PCI) Registry
The pilot phase of INTERSTROKE, conducted to                       collecting standardised procedural and follow up data
demonstrate the feasibility of such a large study in               on consecutive patients across multiple sites in Victoria.
stroke, has recently been completed with more than                 The MIG registry helped to inform the ACPR pilot project
2800 participants recruited from 15 countries (Australia,          that was undertaken in 2009, however as yet the ACPR
Argentina, Brazil, Canada, Chile, China, Colombia,                 project is not funded in an ongoing fashion. The MIG study
Denmark, Germany, Ghana, India, Mozambique, Poland,                informed the dataset and many of the sites also
South Africa and Uganda). Results from the Pilot Study             participated as pilot ACPR sites.
will be presented at the European Stroke Conference
in Barcelona in May 2010.                                          Current enrolment sits at 12,914 PCI procedures.
                                                                   Thirty day and twelve month follow up are undertaken
                                                                   routinely on all subjects. Longer term outcome data is
                                                                   now available as linkage with National Death Index has
                                                                   been undertaken in 2009.

                                                                       Centre of Cardiovascular Research and Education in Therapeutics | 11
        This data will be reported upon in 2010 with abstract and      ASCTS
        manuscripts planned that will extensively utilise this data.   The Australian Society of Cardiothoracic Surgeons
        In 2009, MIG continued to present widely at national and       (ASCTS) National Cardiac Database Program records
        international cardiology meetings. In addition to the          details of all adult cardiac surgical procedures performed
        13 manuscripts already published, several more are             in participating units across Australia. The program
        either in review or well underway.                             publishes annual reports describing the activities and
                                                                       outcomes of participating units in a comparative,
        MIG continues to collaborate widely, especially with           de-identified format.
        the cardiac surgeons and the ASCTS registry.
                                                                       Currently, 18 of 25 Public Hospital Units are members of
        Publications                                                   the program and four private hospitals are also participating
        Reid CM, Ajani AE, Eccleston D. Why we need a national         in the registry. Since the instigation of the project in 2001,
        registry in interventional cardiology. Med J Aust. 2009 Feb    the ASCTS web database portal contains over 35,000
        2;190(3):162–3.                                                records. To date, 13 manuscripts arising from the project
                                                                       have been published including papers on an Australian
        Yap CH, Yan BP, Akowuah E, Dinh DT, Smith JA,                  Risk Prediction Model for Coronary Surgery, on the short
        Shardey GC, Tatoulis J, Skillington PD, Newcomb A,             and longer term outcomes and in collaboration with
        Mohajeri M, Pick A, Seevanayagam S, Reid CM.                   other interventions.
        Does prior percutaneous coronary intervention adversely
        affect early and mid-term survival after coronary artery       Publications
        surgery? JACC Cardiovasc Interv, 2009; 8:758–64.               Brasacchio D, Dinh DT, Billah B, Shardey G, Reid CM
                                                                       on behalf of the Australian Society of Cardiac and Thoracic
        Gurvitch R, Lefkovits J, Warren RJ, Duffy SJ, Clark DJ,        Surgeons Database Project Steering Committee. Cardiac
        Eccleston D, Yan BP, Reid C, Brennan A, Andrianopoulos N,      Surgery in Victorian Public Hospitals 2007-2008: Hospital
        Ajani AE. Clinical outcomes of drug eluting stent use in       Report. Quality and Safety Branch, Department of Human
        high risk patients with ST elevation Myocardial Infarction.    Services, Melbourne Victoria 2009.
        Int J Cardiol, 2009 (Epub ahead of print)
                                                                       Brasacchio D, Dinh DT, Billah B, Shardey G, Reid CM
        Lim H, Farouque O, Andrianopoulos N, Yan B, Lim C,             on behalf of the Australian Society of Cardiac and Thoracic
        Brennan A, Reid C, Freeman M, Charter K, Black A New           Surgeons Database Project Steering Committee. Cardiac
        G, Ajani A, Duffy S, Clark D. Survival of elderly patients     Surgery in Victorian Public Hospitals 2007–2008: Report
        undergoing percutaneous coronary intervention for acute        to the Public. Quality and Safety Branch, Department of
        myocardial infarction complicated by cardiogenic shock.        Human Services, Melbourne, Victoria 2009.
        Journal of American College of Cardiology Interventions,
        2009;2:146–152.                                                Brasacchio D, Dinh DT, Billah B, Shardey G, Reid CM
                                                                       on behalf of the Australian Society of Cardiac and Thoracic
        Freeman M, Clark D, Andrianopoulos N, Duffy S, Lim H,          Surgeons Database Project Steering Committee. Cardiac
        Brennan A, Charter K, Shaw J, Horrigan M, Ajani A,             Surgery in Australian Hospitals 2007–2008: National
        Sebastain M, Reid C, Farouque O. Procedural and clinical       Report. Melbourne, Victoria 2009.
        outcomes of percutaneous coronary intervention for ostial
        lesions in proximal coronary arteries. Catheterization and     Dinh DT, Di Giambattista K, Billah B, Shardey G,
        Cardiovascular Intervention, 2009;73:763–768.                  Reid CM on behalf of the Australian Society of Cardiac
                                                                       and Thoracic Surgeons Database Project Steering
        Butler MJ, Eccleston D, Ajani A, Lefkovits J, Clark DJ,        Committee. Cardiac Surgery in NSW Public Hospitals
        Andrianopoulos N, Brennan A, Reid CM, Farrington C,            2007– 2008: NSW Service Report. Greater Metropolitan
        Walton AS, Dart AM, Duffy SJ, on behalf of the Melbourne       Clinical Taskforce, NSW Health, Melbourne, Victoria 2009.
        Interventional Group (MIG). The effect of intended duration
        of clopidogrel use on early and late mortality and major       Yap C-H, Andrianopoulos N, Dinh DT, Billah B, Rosalion AM,
        adverse cardiac events in patients with drug-eluting stents.   Reid CM. Short and mid-term outcomes of coronary
        American Heart Journal, 2009;157(5):899–907.                   artery bypass surgery performed by surgeons in training.
                                                                       The Journal of Thoracic and Cardiovascular Surgery.

12 | Annual Report 2009
Yan BP, Clark DJ, Buxton B, Ajani AE, Smith JA, Duffy SJ,         including Australia. The further aim is to compare
Shardey GC, Skillington PD, Farouque O, Yii M, Yap C-H,           outcomes within different subject profiles and define
Andrianopoulos N, Brennan A, Dinh D, Reid CM,                     predictors of risk for subsequent events. In Australia,
on behalf of the Australasian Society of Cardiac and              2873 participants were recruited with excellent follow up
Thoracic Surgeons (ASCTS) and the Melbourne                       of 99 per cent at Year 1 and 98 per cent at Year 2. Recent
Interventional Group (MIG). Clinical characteristics and          publications have focussed on one year clinical outcomes
early mortality of patients undergoing coronary artery            for Australian patients identifying the increased adverse
bypass grafting compared to percutaneous coronary                 outcomes associated with those not following evidence-
intervention: Insights from the Australasian Society of           based guidelines in relation to the use of statins and
Cardiac and Thoracic Surgeons (ASCTS) and the                     aspirin. Further work has been undertaken with a health
Melbourne Interventional Group (MIG) registries.                  economic analysis of greater utilisation of clinical outcomes
Heart Lung and Circulation. 2009;18(3):184–90.                    and looking at the impact of obesity on costs in the
                                                                  Australian community.
Australian Rheumatology
Association Database (ARAD)                                       Publications
The Australian Rheumatology Association Database                  Ademi Z, Liew D, Chew D, Conner G, Shiel L, Nelson M,
(ARAD) is a national Australian database which collects           Soman A, Steg G, Bhatt DL, Reid C; REACH registry
important health information from individuals with                investigators. Drug treatment and cost of cardiovascular
inflammatory arthritis. The aim of the registry is to determine   disease in Australia. Cardiovasc Ther. 2009 Fall;27(3):
the short and long term effectiveness and safety of new           164–72.
biological disease-modifying anti-rheumatic drugs used
to treat inflammatory arthritis conditions.                       ANZIC-RC Collaborations
                                                                  The Clinical Informatics and Data Management Unit
CCRE Therapeutics provides data management for                    provide data management services for a number of
the ARAD registry. Information is collected via six monthly       investigator-initiated clinical studies being undertaken
completed questionnaires, which include questions about           by the Australia and New Zealand Intensive Care Research
medical history, medication history, responses to medication,     Centre (ANZIC-RC). Actively recruiting studies during 2009
physical functioning and quality of life. CCRE Therapeutics       included the STATInS study; a phase II randomised
has recently developed a web-based system which allows            controlled trial of atorvastatin therapy in intensive care
individuals to complete their 6 monthly questionnaire             patients with severe sepsis, and the INFINITE study;
on-line, which has been very well received by participants.       a ‘real time’ registry of all patients admitted with Influenza
                                                                  A to Australian and New Zealand ICUs between 1 June
Patients and rheumatologists across Australia contribute          2009 to the end of winter 2010. New endorsed trials that
to ARAD, with over 3000 participants actively completing          are in development and due to commence in early 2010,
questionnaires and over 200 rheumatologists referring             include POLAR; a study of the early use of induced
patients to ARAD.                                                 hypothermia in closed head injuries to improve outcomes,
                                                                  and EPO-TBI; determining the efficacy of erythropoietin in
Publications                                                      improving neurological function after traumatic brain injury.
Briggs AM, March L, Lassere M, Reid C, Henderson L,
Murphy B, van den Haak R, Rischin A, Staples M,                   Sentinel Surveillance Study
Buchbinder R. Baseline Comorbidities in a Population-             The Sentinel Study is a linked sentinel survey of chlamydia,
Based Cohort of Rheumatoid Arthritis Patients Receiving           HIV, syphilis and hepatitis C in Victoria developed by the
Biological Therapy: Data from the Australian Rheumatology         Burnet Institute and undertaken in collaboration with the
Association Database. Int J Rheumatol. 2009;                      Department of Human Services Victoria, the Victorian
Epub ahead of print.                                              Infectious Disease Reference Laboratory and the
                                                                  Melbourne Sexual Health Centre.
The REACH registry is an international prospective                CCRE Therapeutics is undertaking data management for
observational registry of subjects at risk of                     this project that will be used to monitor HIV, hepatitis C
atherothrombotic events. In Australia, the CCRE                   and sexually transmitted infection incidence, prevalence,
Therapeutics has been the national coordinating centre            risk behaviour and testing patterns in order to inform
and the study has been conducted at 274 sites in Victoria,        and evaluate relevant public health strategies. In 2009,
NSW, QLD, SA and WA. The primary aim of this study was            there is ongoing data linkage between Melbourne Sexual
to evaluate the long-term risk of atherothrombotic events         Health Centre for quarterly data extraction in addition to
globally as well as in different population sub-groups            continuing data collection from 16 sites across Victoria.

                                                                   Centre of Cardiovascular Research and Education in Therapeutics | 13
        Cabrini Colorectal Database Project                            Australian Cardiac Procedures Registry (ACPR)
        In collaboration with Associate Professor Paul McMurrick,      The ACPR pilot began in 2008 with the purpose of
        this is a project to develop a web-based data collection       monitoring the safety and quality of cardiac procedures.
        process for colorectal surgical cancer procedures at           Funding for the pilot was provided by the Australian
        Cabrini Hospital. The aim of this project will be to enable    Commission on Safety and Quality in Health Care
        a systematic collection of surgical and outcomes data          (ACSQHC). The aim of the pilot was to test and validate
        which will be able to be linked with other clinical datasets   the draft ‘Operating Principles and Technical Standards
        to provide a facility for Cabrini to undertake clinical        for Australian Clinical Quality Registries’.
        research activities in this area of surgery.
                                                                       It is anticipated that the establishment of the ACPR
        TRIAGE                                                         registry will lead to an improvement in clinical services
        The primary aim of the study is to improve the accuracy        provided and provide the mechanism for the benchmarking
        and speed of diagnosis of congestive heart failure (CHF)       of performance in the delivery of quality of care.
        and acute coronary syndromes (ACS) in the Emergency
        Department. The study will compare the Biosite Triage          Minimum core datasets were developed across three
        SOB panel (using Troponin I, Myoglobin, CKMB, D-dimer,         areas – Percutaneous Coronary Interventions (PCI),
        BNP) with clinical assessment (history and physical            Cardiac Surgery and Implantable Cardioverter Defibrillator
        examination) for the presence or absence of CHF,               (ICD) devices and Cardiac Resynchronisation Therapy
        ACS and pulmonary emboli in patients presenting                (CRT) devices. The Surgery and PCI datasets were
        with breathlessness with or without chest pain.                modelled on the Australian Society of Cardiothoracic
        The primary endpoint will be the presence of CHF               Surgeons Victorian database project and the Melbourne
        and/or ACS as defined by standard criteria (chest              Interventional Group PCI registry, with the device
        X-ray, ECG, laboratory-based CK plus CK-MB or                  dataset a new development.
        troponin, echocardiogram).
                                                                       Eleven sites across four states participated in the ACPR
        A total of 703 patients were enrolled through                  pilot, with data collection commencing in July 2009.
        eight metropolitan and regional hospitals nation-wide.
        Participant follow ups were conducted at 24 hour,              The final report was delivered to the ACSQHC in
        30 day and 6-to-12 month time periods. The final               November 2009. The funding of the ACPR pilot project
        follow ups were completed in 2009 and this data                by the ACSQHC has led to a number of key outcomes
        is currently being finalised. Abstracts utilising 30 day       in the quest to provide information on the quality of care
        outcome data have been presented nationally and                in the provision of high-cost, high-risk cardiac services in
        internationally with longer term outcome data to               Australia. Firstly, it has provided the structure for clinical
        be presented in 2010.                                          leadership and stakeholders to meaningfully engage in the
                                                                       process and secondly, it has provided the process through
        ASia Pacific Evaluation of                                     which standardised data can be collected through a
        Chest pain Trial (ASPECT)                                      secure web-based system developed and operating
        The purpose of this study is to validate a clinical pathway    according to regulatory standards.
        (‘accelerated chest pain algorithm’) of using ECG and/or
        Risk Stratification Tools in conjunction with serial           As part of the pilot a literature review on funding models
        biomarkers (with blood levels of Troponin I, CKMB              for clinical quality registries was conducted. This review
        ‘Delta’, and Myoglobin ‘Delta’ measurements) in                formed the basis of potential financial strategies for
        patients presenting with ACS.                                  sustainable funding which are currently being investigated
                                                                       further. It is hoped that a sustainable funding model will
        Recruitment began at the end of 2008 and is almost             inform the structure of future clinical quality registries.
        complete. Over 2900 subjects have been recruited
        out of an expected 3400.                                       Funding
                                                                       Australian Commission on Safety and Quality in Healthcare
        Preliminary data has been presented at national and            2008 to 2009 – $931,686
        international biomarker meetings.

        Site auditing commenced in late 2009 and will continue
        into 2010. All sites will be visited by CCRE staff who have
        been trained to undertake the audit activity.

14 | Annual Report 2009
Pharmacoepidemiology/                                             A strength of the clozapine and myocarditis study is that
                                                                  environmental and host risk factors which may modify
Translational Research                                            the genetic risk are being documented along with the
                                                                  characteristics of the myocarditis such as measures
Clozapine and Myocarditis Study                                   of severity and involvement of organs besides the heart.
Clozapine is the most effective drug available for
schizophrenia, and also the safest when mortality is              The Cardiovascular Disease Epidemiological
used as the measure. However, in about two per cent               Modelling Project
of patients, it causes a life-threatening adverse effect,         This project is supported by an ARC-Linkage grant with
called myocarditis, in the first few weeks of therapy.            industry partner sanofi-aventis, and is being conducted in
Myocarditis is inflammation of the heart muscle and               collaboration with colleagues at Baker IDI and St Vincent’s
it occurs as a hypersensitivity reaction with clozapine.          Hospital Melbourne. The Cardiovascular Disease
                                                                  Epidemiological Modelling Project uses innovative
The purpose of this study is to identify risk factors for         statistical modelling techniques to model the burden
myocarditis, including a genetic marker. If the risk factors      of cardiovascular disease, obesity and diabetes in
are known, it will be possible to prescribe the drug more         Australia, and also aims to examine the effectiveness
freely to those not at risk.                                      and cost-effectiveness of potential interventions to
                                                                  prevent these chronic diseases and their sequelae.
The study has a case-control design with four controls            The ARC-Linkage granting scheme has a strong focus
for each case. Controls are matched to cases by the unit          upon training of future research leaders and this grant
at which they started clozapine and by approximate start          includes scholarship funding for a PhD candidate,
date to control for variations in prescribing practice. Cases     Ella Zomer. During 2009, the calibre of Ella’s research
and controls are documented from the patient’s medical            was recognised with acceptance of two oral presentations
records. Most patients start clozapine as inpatients which        at the European Society of Cardiology Congress.
means that comprehensive and detailed information is
available on daily doses of clozapine, concomitant medication,    Major activities of this project during 2009 included
daily vital signs, pathology results, smoking status and          validation and calibration of cardiovascular risk prediction
concurrent disease. The cases and controls are required           equations in a number of Australian population settings
to meet strict criteria to ensure the integrity of the study.     and development of a detailed model of examining risk
                                                                  of cardiovascular disease in an Australian population
The aim is to include 100 cases and 400 controls.                 group with metabolic syndrome.
At the end of 2009, 91 cases and 158 controls were
fully documented and samples for DNA extraction had               Funding
been received from 34 individuals.                                ARC Linkage Grant
                                                                  2007 to 2009 – $212,000
A preliminary analysis of data up to the end of 2008
(66 cases, 78 controls) suggests that concurrent sodium           INTEGRATE
valproate and high rates of clozapine dose titration may          The INTEGRATE study is a clinical audit program examining
predispose to myocarditis. Use of zuclopenthixol may              the evidence-based management of hypertension in a
be protective. These effects account for only about               community setting, which is being conducted by CCRE
10 per cent of the risk of myocarditis. The vast majority         in association with Bristol-Myers Squibb. The INTEGRATE
of cases were initiated on clozapine according to the             study has involved participation by both General Practitioners
dosing protocol and were not taking sodium valproate.             (GP) and their patients Australia-wide, and aims to
While there may be other environmental and host                   examine the factors associated with achievement of
factors influencing risk, this result suggests that genetic       blood pressure targets in patients with hypertension.
predisposition may account for as much as 50 per cent             The INTEGRATE study included a GP education program
of the risk of clozapine-induced myocarditis.                     designed to address issues relating to achievement of
                                                                  blood pressure targets, and following the roll-out of the
Genetic factors for other drug hypersensitivity reactions         education program in early 2009, the second and final
have been identified. In three examples, 100 per cent             phase of data collection was undertaken in mid-late
of those developing the reaction had the genetic marker           2009 utilising web-enabled data capture technology.
which was located on the HLA-B region of chromosome 6.
In the fourth example, flucloxacillin-induced liver injury, the   Funding
predisposing genetic factor was also in the HLA-B region,         BMS
and 84 per cent of cases were positive for the genotype.          2007 to 2009 – $389,499

                                                                   Centre of Cardiovascular Research and Education in Therapeutics | 15
        Caulfield Clinical Trial Centre

        The Caulfield Clinical                                          Countering the potential beneficial effects of aspirin
                                                                        therapy are the risks associated with bleeding which
        Trial Centre acts as our                                        are likely to increase as people age. With the composite
                                                                        endpoint of extension of disability-free life years, ASPREE
        community-based research                                        will determine the balance of benefit versus risk of aspirin.
                                                                        If it is proved effective, the low cost of aspirin therapy
        clinic. Most of the studies                                     would make it an affordable preventive agent for elderly

        involve working with                                            populations in all countries.

        general practitioners                                           During 2009, the National Institute on Aging which is one
                                                                        of the National Institutes of Health in the USA approved
        across Melbourne and                                            a major funding application for ASPREE. This was a joint
                                                                        submission from Australian ASPREE researchers, headed
        Australia as well as with                                       by Professor John McNeil, and colleagues from the USA,

        healthy volunteer subjects                                      headed by Professor Richard Grimm of the Berman Center
                                                                        of Outcomes Research in Minneapolis. There will be
        who donate their valuable                                       25 hubs in the USA recruiting participants for ASPREE
                                                                        with a focus on minorities groups (African-Americans
        time to assisting with                                          and Hispanics).

        our research.                                                   The NIH awarded USD$50 million over seven years and
                                                                        this funding will begin in 2010. During the scientific reviews
                                                                        by the NIH, the ASPREE Protocol and numerous other
        Project highlights for                                          documents were revised and changed to incorporate

        2009 are as follows:                                            the US collaborators and their site-specific requirements.
                                                                        At the end of 2009, the NIH-constituted Data and Safety
                                                                        Monitoring Board reviewed all the ASPREE documents
        ASPirin in Reducing Events in the Elderly                       and approved the study to begin new recruiting early
        (ASPREE)                                                        in 2010. One hundred and seventy existing ASPREE
        ASPREE is a large-scale, double-blind randomised,               participants will constitute a Vanguard group for the
        placebo-controlled trial of low dose aspirin for primary        study in Australia, most of whom will have their first
        prevention of disease in healthy older people. The major        annual visit in 2010.
        research question is ‘does low-dose aspirin prolong
        healthy, disability-free life in those aged 70 years and        Publications
        over?’ ASPREE will be conducted in general practices            Woods RL, Tonkin AM, Nelson MR, Reid CM.
        across Victoria, Tasmania and the ACT and will therefore        Should aspirin be used for the primary prevention of
        represent the ageing population in urban and rural Australia.   cardiovascular disease in people with diabetes [editorial]?
                                                                        Medical Journal of Australia, 2009;190:614–615.
        The ASPREE clinical trial will involve 19,500 participants
        who will be randomised to daily 100mg of enteric-coated         Woods RL, Nelson MR, Tonkin AM, Reid CM. In reply:
        aspirin or placebo. Follow up is planned for an average         Should aspirin be used for the primary prevention of
        of five years. The trial methods are based on the highly        cardiovascular disease in people with diabetes [editorial]?
        successful Second Australian National Blood Pressure            Medical Journal of Australia, 2009;191(6):356–357.
        study (ANBP2) that was based in general practices in
        Australia with the practitioner as co-investigator. Low-dose    Funding
        aspirin may be one of the most chemo-effective agents in        NIH (USA) Grant
        older people to prevent or delay the onset of cardiovascular    2009 to 2015 – US$50,445,006
        disease, stroke, dementia and certain cancers, particularly
        bowel cancer. These diseases are the most common                NHMRC Project Grant
        causes of physical and mental disability and hospitalisations   2005 to 2009 – $3,503,500
        amongst the elderly Australian population.

16 | Annual Report 2009
ASPREE Healthy Ageing Biobank                                  The ASPREE Healthy Ageing Biobank Cluster
The ASPREE Healthy Ageing Biobank is a unique                  Management Committee held its first meeting in
opportunity to evaluate new preventive biomarkers of           November 2009 with all cluster parties in attendance.
disease in the elderly. Healthy participants aged 70 and       Parties include CSIRO, Monash University, University
over will be followed annually to ascertain cardiovascular     of Melbourne, University of Tasmania (Menzies Research
events, cognitive decline, cancer incidence, physical          Institute) and Australian National University.
disability and other chronic diseases. The ASPREE
Biobank study aims to collect blood and urine samples
at baseline on all participants to establish a repository of
blood and urine from healthy older people who have not
developed major diseases. Partners in this venture are
the CSIRO, the University of Melbourne, the University
of Tasmania and the Australian National University.
The ASPREE Biobank will be particularly well suited
for the evaluation of new predictive biomarkers
for several reasons:

•   the large number of older subjects will produce
    statistically significant results within a much shorter
    time-frame than cohorts with younger participants;

•   repeated cognitive function assessments will provide
    a unique opportunity to identify biomarkers for
    Alzheimer’s disease and other causes of dementia;

•   the annual or biennial clinical review will provide
    an excellent opportunity to accurately identify            Funding
    other clinical endpoints eg, colon cancer; and             NHMRC Equipment
                                                               2009 – $90,000
•   the prospective design will allow biological samples
    to be collected, processed and stored in the most          Aspirin for the prevention of cognitive decline
    favourable fashion for analysis of new biomarkers          in the Elderly: a Neuro-Vascular Imaging Study
    and potential diagnostics for chronic diseases,            (ENVISion)
    particularly those prevalent in the elderly.               ENVISion is a sub-study of the large-scale clinical trial,
                                                               ASPREE, and involves collaboration between researchers
2009 Progress                                                  from the Department of Epidemiology and Preventive
In addition to the completion of renovations at The Clinical   Medicine, and Chief Investigators Professor Elsdon Storey
Trial Centre (CTC) at Caulfield Hospital, two additional       (Monash University), Associate Professor Marc Budge
regional Biobank processing centres were established in        (Australian National University (ANU), and Professor
2009. Collaborations with ASPREE researchers at ANU            Tien Wong (Centre for Eye Research Australia (CERA),
and the University of Melbourne and pathology providers        University of Melbourne). Awarded an NHMRC Project
at Canberra Hospital and Goulburn Valley Health facilitated    Grant in 2007, the ENVISion study is examining whether
set up of the ASPREE Healthy Ageing Biobank in Canberra        regular low-dose aspirin reduces the rate of increase of
(ACT) and Shepparton (Regional Victoria). Plans are also       brain Magnetic Resonance Imaging (MRI)-based white
underway to set up an additional processing centre at          matter hyperintensity and silent brain infarction volumes
Hobart in collaboration with Professor Mark Nelson at          in otherwise healthy elderly Australians. Brain MRI changes
the Menzies Research Institute.                                correlate with white matter ischaemia, and may provide an
                                                               efficient surrogate for cognitive decline. However, MRI is
The Biobank protocol underwent a minor amendment               relatively costly and is not universally accessible, making it
in 2009 to include the collection of a urine sample from       impractical for population screening. The retinal vasculature
participants. The collection of urine will allow for testing   shares many features with that of the brain. If changes in
of biomarkers in the future that cannot be tested for in       the two were found to be highly correlated, retinal digital
the blood components that are being collected and              photography would provide the opportunity to combine a
stored. Three participants were enrolled in the study          relatively inexpensive, widely available tool with automated
in late 2009.                                                  analysis to select those likely to benefit most from a

                                                                Centre of Cardiovascular Research and Education in Therapeutics | 17
        preventative intervention (eg regular low-dose aspirin         was employed to identify individuals likely to develop
        treatment). The sub-study will also examine whether            chronic heart failure (CHF) focusing on risk factors
        structural changes in brain and/or retinal vasculature         such as coronary artery disease, valvular heart disease,
        correlate with a decline in cognitive function. ENVISion       hypertension and diabetes.
        is being conducted in 600 people who have consented
        to participate in ASPREE (300 participants in Canberra         CHF is a major burden on the community due to the poor
        and 300 in Melbourne).                                         quality of life and premature death of affected individuals,
                                                                       as well as the costs of care. CHF prevalence is increasing
        During 2009, recruitment of ENVISion study participants        due to the ageing of the population and the improved
        was halted pending the outcome of a grant re-submission        survival from myocardial infarction (MI) and CHF.
        to the NIH seeking international funding for the parent        The increasing prevalence of obesity and diabetes,
        study, ASPREE. With the recent announcement in October         coupled with uncontrolled hypertension, is also likely
        of significant funds (USD $50 million), and the subsequent     to accelerate CHF incidence. Effective therapies for the
        review and approval of the ASPREE study protocol by the        treatment and prevention of CHF are readily available,
        NIH’s appointed Data Safety and Monitoring Board,              and there is great potential to cost-effectively improve
        the stage is now set in 2010 to resume active recruitment      the application of these therapies through improved
        of ASPREE and ENVISion participants. Despite this delay        identification of two key patient groups: those with
        to recruitment, there has been ongoing ENVISion activity       unrecognised CHF, and those at greatly increased risk
        in the past year: members of the ENVISion Steering             of CHF due to LVD. Thus, early detection of disease
        Committee attended monthly teleconferences (as well            could lead to more effective use of beneficial therapies,
        as one face-to-face meeting) to discuss and resolve            reducing the total burden of symptomatic heart failure
        operational issues; the ENVISion Collaborative Agreement       and thus the need for high cost devices.
        between ANU, Monash University and CERA was executed;
        standard operating procedures were amended to include          Forty-four thousand clients of the health insurance company,
        the reporting and follow up of any MRI or retinal vascular     HBA, and members of the general public, aged 60 and
        imaging abnormalities; a training workshop was conducted       over, were invited to participate in the study if they had
        during the two-day official launch of the ASPREE and           not been previously diagnosed with heart failure but had
        ENVISion studies in February to ensure standardisation         one or more risk factors for heart failure (such as a heart
        in the administration of neuropsychological assessments;       attack, stroke, diagnosed hypertension or diabetes).
        and a GP dinner was held in Canberra in November to            Approximately 11,000 HBA clients responded to the
        promote the studies and to facilitate GP recruitment.          study invitation and just over 4000 study participants were
        In Melbourne, ENVISion participants currently visit the        successfully recruited for the study from mid-2007 to 2009,
        Clinical Trial Centre, Caulfield for retinal photography       attending study visits in Melbourne and Shepparton and
        and cognitive function assessments (in addition to             NT-proBNP, routine bloods and information relating to
        ASPREE-related measurements), with brain MRI                   medical history, concomitant medications, physical and
        conducted at the Alfred Hospital.                              demographic information was collected. Those with
                                                                       NT-proBNP in the upper quintile (approximately
        Funding                                                        700 participants) were further assessed for cardiac
        NHMRC Project Grant                                            function via ECG and echocardiographic examination.
        2008 to 2012 – $1,271,102                                      The cross-sectional study was supported by BUPA
                                                                       Australia Group (comprising BUPA Australia Health Pty Ltd
        SCREEN-HF                                                      and MBF Australia Pty Ltd). This cross-sectional study will
        (SCReening Evaluation of the Evolution                         undergo final analysis in 2010. Highlights of 2009 were
        of New Heart Failure)                                          presentations at 57th Annual Scientific Meeting CSANZ
        This prospective, cross-sectional study aims to assess         and European Society of Cardiology meetings.
        the utility and cost-effectiveness of NT-B-type natriuretic
        peptide (NTpro-BNP) in the determination of left ventricular   SCREEN-HFL – a longitudinal study
        dysfunction in patients at high-risk for this condition but    The study investigators, in collaboration with St Vincent’s
        without known cardiac dysfunction, symptoms of heart           Research Institute and St Vincent’s Health, were successful
        failure or previous diagnosis of either condition.             in gaining funding from the NH&MRC to allow a five-year
        NT-proBNP is a hormone released from the heart in              longitudinal follow-up of the entire SCREEN-HF study
        response to pressure or stretch and as such, it is a useful    cohort and early in 2009 ethics approval was gained
        marker of left ventricular dysfunction (LVD), even in the      to commence the longitudinal study. The objective of
        absence of accompanying symptoms. A simple strategy            this longitudinal study is to establish the utility of plasma

18 | Annual Report 2009
NT-proBNP level, and change in NT-proBNP level, in the            ANBP2 was conducted in general practices throughout
identification of individuals with CV risk factors destined       Australia, with recruitment taking place between April
to develop CHF and/or echocardiographic evidence                  1995 and June 1998. In total, 6083 subjects (mean age
of LVD during five years of observation.                          of 71.9 years at baseline) were enrolled in the study from
                                                                  1594 general practices and followed for a median of
All of the 4000 participants from the SCREEN-HF                   4.1 years. The results of ANBP2 showed that initial
cross-sectional study are to be approached to take part           treatment based on ACE inhibitor therapy provided
in the longitudinal and by the end of 2009, 1117 had              an 11 per cent reduction on all cardiovascular events
consented to participate in the longitudinal study. They          or death from any cause in comparison to basing
have attended either CTC or St Vincent’s Hospital for the         treatment on a diuretic.
study assessments including ECG and echocardiographic
examination. It is anticipated that there will be approximately   The ANBP2 Follow-up Study is examining the risk
3500 participants in the longitudinal study and that study        of heart failure in older Australians with hypertension
visits in Shepparton will occur during 2010. Blood samples        (high blood pressure). This study is designed to undertake
are collected and stored for later measurement of novel           a prospective cohort 10 year follow up study of all subjects
cardiovascular biomarkers.                                        in ANBP2 (who consented to follow up) with the primary
                                                                  aim being to determine the rate of all-cause and
The main features of the five-year SCREEN-HF                      cardiovascular mortality and morbidity in this elderly
longitudinal study are:                                           hypertensive population. In addition, the study will
                                                                  determine the progression from hypertension to CHF
•   All SCREEN-HF study participants will be invited to           of the population and the effect of initiating treatment
    participate in the five year longitudinal study, which will   based on ACE inhibitor versus that based on diuretic on
    collect five years of longitudinal data, with a second        subsequent CHF, together with healthcare utilisation and
    echocardiographic and clinical examination performed          costs associated with this management of these elderly
    three years after the first examination. The second           Australian hypertensives. This will permit modelling of
    echocardiographic examination will be performed               healthcare resource requirements in an ageing cohort
    approximately three years after the first because it will     and quantification of disease burden in an elderly
    take three years to perform 3500 echocardiographic            Australian cohort.
    examinations, and we aim to complete the second
    examination for all 3500 subjects within the five-year        The ANBP2 participants, who gave consent at the
    duration of this project.                                     end of the ANBP2 study for further contact, were sent
                                                                  questionnaires in the mail to complete and were also
•   The SCREEN-HF study participants will be invited to           asked to give a questionnaire to their general practitioner
    undergo echocardiographic, ECG, clinical examination          to complete and return. One thousand, seven-hundred
    and quality of life assessments and be reviewed in            and twenty-six participants and 1222 GPs returned
    regards to cardiovascular events, symptoms of                 questionnaires which will allow determination of the
    heart failure and current medications.                        long-term cardiovascular consequences of antihypertensive
                                                                  treatment, comparing outcomes in those randomised to
Funding                                                           treatment with ACE-inhibitors with those treated with
NHF Grant-in-Aid                                                  diuretic agents. Through data linkage with the National
2008 to 2009 – $126,671                                           Death Index and re-contacting of participants 10 years
                                                                  after completion of the original study, it was ascertained
The Second Australian National Blood Pressure                     that approximately 32 per cent of the original study
(ANBP2) Follow up Study                                           participant cohort have died. In 2010, Melbourne
The Second Australian National Blood Pressure Study               metropolitan participants will be invited to attend the
(ANBP2) was a randomised controlled trial designed and            CTC for further follow-up including an ECG and
conducted by the High Blood Pressure Research Council             echocardiographic examination.
of Australia. It was designed to determine if there was any
difference in outcome (defined by total cardiovascular            Funding
events and mortality) between elderly hypertensive                NHMRC General Practice Clinical Research Program
patients, aged 65 to 84 years, who were randomised to             2008 to 2009 – $192,000
active treatment with an angiotensin-converting enzyme
(ACE)-inhibitor based-regimen or treatment with a
diuretic-based antihypertensive regimen.

                                                                   Centre of Cardiovascular Research and Education in Therapeutics | 19
        ARMCAD (Alternative Risk Markers in Coronary                    CLEAR (Cardiovascular Longitudinal Evaluation
        Artery Disease)                                                 and Assessment of Risk)
        This prospective observational study recruited 550 patients     This study is a cross-research database to incorporate
        referred for invasive coronary angiography in three Melbourne   current and future investigator-driven studies at CCRE.
        cardiology centres, irrespective of co-morbidities. The aims    The aims are to improve data collection, standardise
        of the project are:                                             cardiovascular risk information and enhance recruitment
                                                                        into research projects. Future CCRE studies will
        1. to better understand the effects of risk factor              incorporate the use of standardised case report forms.
           modification on prediction and stratification of             Participants, at the time of recruitment, will be consented
           the risk of coronary artery disease (CAD); and               to include their study data in the CLEAR database,
                                                                        allowing long-term follow up of cardiovascular morbidity
        2. the clinical impact of novel and non-invasive markers        and mortality. Currently, clinical trials have a finite follow up
           such as pulse wave analysis, heart rate variability and      period; the CLEAR study involves lifetime follow up and
           pulse wave velocity.                                         will establish a cohort of volunteers suitable for recruitment
                                                                        into future studies. The project commenced in 2007 with
        Diagnostic coronary angiography is the gold-standard for        the incorporation of the ARM-CAD and SCREEN-HF studies.
        identifying coronary atherosclerosis. Risk factor assessment
        combined with stress-testing and nuclear imaging is often       HOPE-3 (Heart Outcomes Prevention Evaluation)
        used for risk-stratification and to determine the need and      HOPE-3 is a five-year multinational double blind longitudinal
        priority for coronary angiography. These tests require          study to evaluate the effects of the ‘polypill’, namely
        substantial resources and despite their use, significant        combined cholesterol and blood pressure lowering,
        coronary artery disease is absent in up to half of patients.    in approximately 11,000 study participants who are
        Angiography itself is associated with serious adverse           without vascular disease at baseline. The study is expected
        events, including death (0.1 per cent), myocardial              to identify safe and effective CV prevention strategies
        infarction (0.1 per cent) and vascular injury or bleeding       which could substantially reduce the risk of CVD in large
        (4 to 8 per cent).                                              proportions of the adult population worldwide.

        Our results have highlighted the important risk factors         The trial participants are those who do not have a clear
        associated with CAD and how novel risk markers can              indication or contraindication to lipid lowering or blood
        be used in a clinical environment to diagnose or exclude        pressure lowering with any of the study drugs. In order
        coronary disease. Results from cross-sectional analysis         to exclude very low risk people, in addition to age, one
        of angiographic disease have been presented at a number         additional CV risk factor is required for eligibility in the trial.
        of international conferences and final manuscripts are          The inclusion criteria for the study are women aged over
        currently under peer-review in major cardiology journals.       60 years and men aged over 55 years, with one additional
        The ARM-CAD study is also recruiting a lower-risk cohort        CV risk factor (such as current or recent smoker, waist/hip
        at the Caulfield Clinical Trial Centre and assessing follow     ratio over 0.90 in men and over 0.85 in women, family
        up of participants to identify incident cardiovascular events   history of premature CHD in first degree relatives (age
        and the predictive capacity of novel risk markers.              under 55 years in men or under 65 years in women).
                                                                        The primary outcome is the composite of CV death,
        Publications                                                    nonfatal myocardial infarction (MI), nonfatal ischemic
        Kotecha D, Flather M, McGrady M, Pepper J, New G,               stroke, resuscitated cardiac arrest and arterial
        Krum H, Eccleston D. Contemporary predictors of                 revascularisations. Follow-up study visits occur
        coronary artery disease in patients referred for angiography.   every six months for an average of at least five years.
        Eur J Cardiovasc Prev Rehabil. 2009 Oct 24.
        [Epub ahead of print]

20 | Annual Report 2009
CTC is recruiting study participants as well as coordinating        SAVE (Sleep Apnea cardioVascular Endpoints)
other sites in Australia: The George Institute for International    The SAVE study is a collaborative, Phase III, multi-centre,
Health, Sydney; The George Institute for International              open-label randomised controlled trial of continuous
Health, School of Rural Health Research Centre, Dubbo;              positive airway pressure (CPAP) for the treatment of
and Dr Geoffrey Robinson (GP practice, Mt Beauty,                   obstructive sleep apnoea (OSA) to prevent cardiovascular
Victoria). In 2010, Dr John Amerena, Geelong and                    disease. The primary objective of the study is to evaluate
Canberra Hospital will also begin recruiting study                  the hypothesis that in patients with moderate to severe OSA,
participants. To date in Australia, twenty-four patients have       CPAP added to standard care will reduce the incidence of
been randomised at CTC, eight at The George in Dubbo                major and minor CV events relative to standard care alone,
and two at The George in Sydney. Recruitment for this               as measured by the composite endpoint cluster of CV
study has been slower than expected worldwide with                  death, myocardial infarction, stroke, hospitalisation for
a total of 6320 participants worldwide being randomised             heart failure and hospitalisation for an acute ischaemic
to the study by the end of 2009. HOPE-3 will recruit study          cardiac event or cerebral event.
participants from about 150 centres in about nine countries.
Recruitment has now been extended to June 2010.                     OSA is a condition in which a person, because of
This investigator-initiated study is conducted by the               relaxation of throat muscles, stops breathing for several
Population Health Research Institute, McMaster University           seconds at a time, many times over, during sleep.
and Hamilton Health Sciences, Canada.                               Research indicates that it may lead to high blood pressure
                                                                    and increase the risk of heart attacks and strokes. One of
HOPE-3 arterial compliance sub-study                                the current treatments available for severe OSA is the use
Funding was obtained from the National Heart Foundation             of CPAP. CPAP involves the use of a small mask placed
(NHF) to conduct a sub-study to assess the independent              over the nose or nose and mouth, during sleep where air
and the combined effects of blood pressure lowering and             is gently pushed into the lungs and allows people to
lipid lowering on arterial stiffness in approximately 300           continue breathing normally. CPAP has been shown
of the HOPE-3 study participants who attend CTC.                    to effectively reduce snoring, obstructive episodes and
                                                                    daytime sleepiness. Some short-term research studies
Prior to receipt of study medication, those subjects willing        have shown that CPAP may help to reduce blood pressure.
to participate in the sub-study will undertake arterial stiffness   This CPAP device is approved in Australia and internationally
assessment at the Clinical Trial Centre. Pulse wave velocity        for use in the treatment of sleep apnoea. Participants are
(PWV) is measured between the carotid artery and the                eligible for the study if they have at least one of the following
femoral artery using non-invasive applanation tonometry.            risk factors for OSA: a previous heart attack; heart disease
Systemic arterial compliance is a non-invasive test of the          requiring bypass graft surgery, angioplasty or stenting;
elasticity of the arteries and involves measurements of             stroke, or a transient ischaemic attack (TIA); or angina.
blood pressure and blood flow using ultrasound
transducers positioned above the sternum to image                   This study is being carried out in about 5000 patients
the ascending aorta. Three study participants have                  world-wide and will last up to five years. Recruitment is
been recruited to the sub-study.                                    continuing and 13 sites in Australia have randomised 53
                                                                    patients and sites in China have randomised 280 patients.
Funding                                                             CTC is the 5th highest recruiting Australian site with seven
NHF Grant-in-Aid                                                    study participants. This investigator initiated study is being
2008 to 2009 – $120,126                                             conducted by an international group of researchers based
                                                                    in China, Europe, USA and Australia. The SAVE International
                                                                    coordinating entre is based at the Adelaide Institute for
                                                                    Sleep Health, Adelaide, South Australia.

                                                                     Centre of Cardiovascular Research and Education in Therapeutics | 21
        STABILITY                                                         KANYINI –GAP (Kanyini Guidelines Adherence
        (The STabilisation of Atherosclerotic plaque                      with the Polypill Study)
        By Initiation of darapLadIb TherapY                               This is a prospective, open, randomised controlled clinical
        This is a randomised, placebo-controlled, double-blind,           trial (n=1000 non-Indigenous and Indigenous individuals)
        parallel-group, multi-centre, event-driven trial of an            of a polypill-based strategy compared to usual care
        investigational product called darapladip, in people with         among individuals at high risk of cardiovascular events
        chronic coronary heart disease receiving standard practice        based in general practices and Indigenous specific health
        care at the time of entry into the study. Coronary Heart          services, augmented by a cost-effectiveness analysis and
        Disease (CHD) is a condition in which deposits of fat and         a formal process evaluation.
        cholesterol, called plaque, build up over time in the heart
        or the blood vessels that supply blood to the heart muscle.       The Kanyini GAP study comprises of two collaborations:
        This build up of plaque is part of a process called               The Kanyini Vascular Collaboration (KVC) is a five year
        ‘atherosclerosis’, or hardening of the arteries. People           health services research program, established between
        with CHD are at risk of having a heart attack or stroke.          Indigenous and non-Indigenous health service and clinical
                                                                          researchers and conducted in close collaboration with
        Darapladip reduces the activity of a naturally occurring          several Aboriginal Community Controlled Health Services
        chemical in the body, an enzyme, called lipoprotein-              (ACCHS) in metropolitan, rural and remote communities
        associated phospholipase A2, or Lp-PLA2. Elevated                 in NSW, NT, and QLD and one government funded
        plasma levels of an enzyme known as Lp-PLA2 are                   Indigenous health service in QLD. The Guidelines
        associated with an increased risk of cardiovascular events.       Adherence with the Polypill collaboration has been formed
        Clinical studies of darapladip have shown dose-dependent          between the George Institute for International Health,
        inhibition (the higher the dose the greater the inhibition) of    the Department of General Practice, Western Clinical
        both plasma and intra-plaque Lp-PLA2 activity. Stopping           School, University of Sydney and CTC, Monash University.
        the production of this enzyme may be beneficial to                These three groups have developed a research collaboration
        cardiovascular patients who are also taking standard              comprising of a diverse network of general practices in
        therapies such as lipid lowering medication called statins.       NSW and Victoria. The CTC is responsible for recruiting
                                                                          approximately 100 non-Indigenous study participants
        This international study aimed to recruit 15,500                  in the Melbourne area in association with local general
        participants randomised to one of two groups.                     practices. Ethics approval was obtained for this study
        Approximately 7750 participants will be allocated to              at the end of 2009 and recruitment will start in 2010.
        the darapladip group and will receive 160mg of enteric
        coated darapladip daily, 7750 participants will receive a         The aim of the study is to assess whether provision of
        placebo daily and will be followed for up to three years.         a polypill (containing low dose aspirin, a statin and two
        The study recruitment was achieved in October 2009,               blood pressure lowering medicines) compared to usual
        with 306 participants at 16 sites in Australia (23 participants   cardiovascular medications improves adherence to
        were recruited by the Clinical Trial Centre – the second          indicated therapies and clinical outcomes among high-risk
        highest recruiting site in Australia). Study participants         patients. Secondary aims are to measure prescription of
        will be followed every six months for approximately               combination therapy, barriers to adherence, quality of life,
        three-and-a-half years. This study is funded by                   safety, cardiovascular events, prescriber acceptability,
        the pharmaceutical company, GlaxoSmithKline.                      and healthcare resource consumption. The study will be
                                                                          conducted within mainstream general practices and the
        Funding                                                           participating health service partners in the Kanyini Vascular
        GlaxoSmithKline Australia Pty Ltd                                 Collaboration. This is an investigator initiated study
        2009 to 2010 – $219,600                                           sponsored by The George Institute for International
                                                                          Health and is funded by an NHMRC grant.

22 | Annual Report 2009
ABIDING (Ankle Brachial Index Determination                       Oscillometric devices allow Ankle-Brachial Index (ABI)
by oscillometric method IN General practice)                      measurement without a Doppler device. We wish to
The ABIDING Study will investigate if the oscillometric           validate these devices in Australian general practice.
determination of ankle brachial index (ABI) by general            Secondary aims of the study are to establish the change
practice nurses is a valid and reliable method. Practice          in prevalence over time of PAD in a defined high risk
nurses have been chosen rather than GPs as, with the              general practice population, to ascertain the utility of
current GP workforce shortage and the promotion of                oscillometric devices for the diagnosis of PAD and to
the concept of a ‘primary care team’ supported by                 monitor the change since baseline of the ABI using the
MBS item numbers for nurses, this is more likely to be            standard technique, BMI, waist circumference measure
implementable. GPs have ready access to oscillometric             and Edinburgh Claudication score. Ethics approval for the
sphygmomanometers as recently oscillometric                       study was obtained and the study began recruiting in late
sphygmomanometers were distributed to GPs through                 2009, with 13 study participants completing study visits.
the High Blood Pressure Research Council of Australia.            This study is funded by an NHMRC grant and is being
                                                                  led by Professor Mark Nelson, University of Tasmania.
The REACH Registry Australian DMC, located at the
Department of Epidemiology and Preventive Medicine,
Monash University, will be used to recruit GP practices
to participate in the study. The REACH Registry was an
international register of those with established cardiovascular
disease or at high risk of it. It was demonstrated in the
REACH Registry that peripheral arterial disease (PAD) is
prevalent in high risk individuals in the Australian primary
care environment. In addition, it was shown that those
with the condition had the highest level of Cardiovascular
Disease (CVD) morbidity and mortality over the
subsequent year.

                                                                   Centre of Cardiovascular Research and Education in Therapeutics | 23
        Research training and education

        Research student reports                                        500 adults, in diverse geographical settings from Alice
                                                                        Springs Town to remote communities and town camps,
                                                                        will undergo full cardiovascular assessment including
        Fourth Year                                                     echocardiograph and ECG. To date, over 170 participants
                                                                        are enrolled and preliminary data shows there is a high
        Dr Michele McGrady                                              prevalence of heart failure risk factors along with
        MBBS, FRACP                                                     ventricular dysfunction and rheumatic heart disease.

        Thesis title                                                    Current progress
        Epidemiology of Left Ventricular Dysfunction                    Recruitment in both these cohorts is complete and
        and Heart Failure in High Risk Populations.                     final reporting is underway along with data analysis
                                                                        and preparation of manuscripts to report findings.
        Heart failure is a major health problem throughout the          Ms Zanfeni Ademi
        world, with high morbidity, mortality and cost to the           MPharm, MPH
        healthcare system. Population estimates of heart failure
        prevalence vary between 2 and 10 per cent, depending            Thesis title
        on the population, and rises significantly as we age.           Using the real world data to inform policy decision makers
        Fifty per cent or greater of those with identifiable left       on the cost of illness and cost effectiveness of treatment
        ventricular dysfunction are asymptomatic, undiagnosed           for cardiovascular disease.
        and often untreated. Prevalence rates may be even greater
        in selected populations, particularly those with a very high    A number of registries have been performed over the years
        prevalence of known risk factors for the condition, such as     in the field of cardiovascular disease. However, not many
        hypertension, myocardial ischemia, diabetes mellitus,           cardiovascular patient registries report the cost data.
        chronic kidney disease and obesity. Effective therapies         Therefore, our aim is to emphasize the significance of
        exist to treat both symptomatic and asymptomatic left           these registries on estimating the cost effectiveness of
        ventricular systolic dysfunction. We have limited data in       treatment as a tool to inform policy decision makers in
        Australia on the prevalence of heart failure, asymptomatic      order to maximise technical and allocative efficiency.
        left ventricular dysfunction and the underlying causes and      We recommend that to expand their spectrum of
        still have much to learn about early diagnosis.                 importance and relevance and to fill these gaps in evidence,
                                                                        cardiovascular registries must report costs data alongside
        Aim                                                             other epidemiological outcomes. The objective was to
        To document the epidemiology and underlying                     identify the main drivers of healthcare costs from the
        characteristics of heart failure and asymptomatic               perspective of the government as the main payer.
        LV dysfunction in two high risk populations as follows:
                                                                        The study applied the bottom up costing approach
        SCReening Evaluation of the Evolution of New Heart              to health expenditures using one year and two year
        Failure (SCREEN HF) – An elderly high risk population           follow up data from Australian subjects recruited into the
        (over 60 years, plus more than one heart failure risk factor)   international REACH Registry. It applied regression and
        without a previous diagnosis of known HF or left                count models to ascertain the impact of cardiovascular
        ventricular dysfunction. Following initial screening            risk factors and outcomes in healthcare costs, and have
        (n=3500), the 700 participants with NT-proB natriuretic         explored the causes of any difference found. In addition,
        peptide (NT-proBNP) in the highest quintile undergo             it used decision analysis tree model to show the difference
        assessment of cardiac structure and function by ECG             in treatment gap between clinical practice and
        and echocardiogram.                                             recommendations with regard to cardiovascular disease.
                                                                        The study has reported these results as the Incremental
        Heart of the Heart – a population based study of                Cost effectiveness ratio per event prevented.
        heart failure and underlying aetiology in the Indigenous
        population of Central Australia. This population has
        three times the mortality from heart failure as the general
        population and a high prevalence of rheumatic heart disease.

24 | Annual Report 2009
Dr Suree Lekawanvijit                                             As AST-120 can reduce a circulating IS level which is
MD (Hons 1), FRCPath                                              increased more in MI animals compared to sham animals.
                                                                  Another animal project using an MI model and AST-120
Thesis title                                                      as treatment has also been conducted alongside the renal
Cardiorenal Syndrome: Pathophysiology and Role                    failure with AST-120 project.
of Protein-Bound Uremic Toxins and Biomarkers.
                                                                  Third Year
Heart Failure (HF) and Chronic Kidney Disease (CKD)               Ms Lavinia Tran
are closely interrelated. Failure of one organ can cause          BBiomedSci (Hons)
dysfunction of the other which in turn accelerates failure
of both, leading to the term ‘cardiorenal syndrome’.              Thesis title
However, the pathophysiology is still unclear.                    Therapeutic targeting of signalling pathways in heart failure.

In the setting of CKD, traditional cardiovascular risk factors    Background
such as hypertension, diabetes and hyperlipidemia alone           Heart failure is a major health burden worldwide and
are not enough to explain the unacceptably high                   places substantial stress on the health care system.
cardiovascular death observed. Since protein-bound
uremic toxins, a subgroup of toxins accumulated in                Lavinia’s PhD project spans across both clinical and basic
patients with CKD, are ineffectively removed by current           science research to determine the mechanisms involved
conventional hemodialysis, we hypothesized that such              in the progression of heart failure and to target these
toxins may have adverse cardiac effects. Indoxyl Sulfate          pathways with novel drugs. The clinical study involves
(IS), one of those toxins, has been demonstrated pro-             an Iontophoresis trial with heart failure patients and healthy
fibrotic and pro-hypertrophic effects on cultured cardiac         controls to test the effects of potential drugs on forearm
cells, for the first time, as well as a pro-inflammatory effect   vascular blood flow. The basic science component utilizes
on monocytic cells. Thus, IS might be implicated in               animal models and primary cell culture to investigate drug
cardiovascular diseases and accelerated death in the              effects. The current findings of this study have been
setting of CKD. This work was presented at AHA Scientific         presented both nationally and internationally.
Sessions 2008 and won the AHA Best Scientific Poster              Lavinia plans to submit her PhD by publication in 2010.
Award (Basic Science). The paper has been accepted
for publication in the European Heart Journal 2010.               Significance of this study
                                                                  This project has the potential to uncover novel therapeutic
Next to this project is to discover how to eliminate the          drugs for the treatment of heart failure and provide further
adverse effects of indoxyl sulfate on the heart by conducting     understanding of the mechanisms that may be relevant in
an in vivo study (renal failure model), using a compound          other cardiovascular diseases.
named AST-120. This compound is an oral adsorbent
having IS-lowering effect in the gut. The aim of this study       Scholarship – National Heart Foundation Postgraduate
is to determine whether AST-120 can improve heart                 Research Scholarship.
function and structural changes in relation to its
IS-lowering effect.

In the setting of HF, the other direction to study cardiorenal
syndrome, study of how the diseased heart affects the
kidney is extremely rare. Therefore, an in vivo project
to systematically study of pathophysiology has been
conducted. Aims are to evaluate changes at structural
and molecular levels in the kidney following Myocardial
Infarction (MI) over time and to identify biomarkers for early
kidney injury in this setting. Renal dysfunction, progressive
renal interstitial fibrosis and an increased Kidney Injury
Molecule-1 (KIM-1) have been identified. This work was
presented at AHA Scientific Sessions 2009.

                                                                   Centre of Cardiovascular Research and Education in Therapeutics | 25
        Ms Ella Zomer                                                  CSL Symposium: Modern Management
        BBiomedSci(Hons)                                               of Heart Failure
                                                                       Chair: Professor Henry Krum
        Thesis title
        Epidemiological modelling of metabolic syndrome                The first speaker was Professor Andrew Coats, Deputy
        and cardiovascular disease in Australia.                       Vice Chancellor (Community) at the University of Sydney
                                                                       whose talk titled ‘Heart Failure: Modern Understanding
        Metabolic Syndrome (MetS) is a group of factors that           of Epidemiology and Treatment’ addressed the growing
        significantly increase the risk of developing cardiovascular   problem of treating heart failure in the elderly. His
        disease and type two diabetes mellitus. With no clear          presentation was followed by Dr Marcus Flather,
        definition it is underpinned by insulin resistance,            cardiologist and Director of the Clinical Trials and
        hyperinsulinemia and obesity together with other               Evaluation Unit, Royal Brompton Hospital, London,
        cardiovascular risk factors. It currently affects              who then addressed the issue of ‘Beta Blockers in Heart
        approximately 20 to 30 per cent of the Australian              Failure: New Data in the Elderly’. Dr Flather (together with
        population and estimated to continue to rise with the          Professor Coats) is a member of the Steering Committee
        aging population and increasing rates of obesity. As there     of the multinational SENIORS study and, in his presentation,
        are many risk factors comprising MetS, confusion surrounds     he provided new data from this study on the effects of
        what component to treat first. This project aims to develop    nebivolol in patients with preserved ejection fraction and
        and use epidemiological (including economic) modelling         impaired renal function. Following the presentations,
        to (i) determine the future landscape of metabolic             Professor Krum led an interesting question and answer
        syndrome and cardiovascular disease in Australian              session and discussion.
        and (ii) identify the most effective and cost effective
        means of preventing and treating cardiovascular disease        Astra Zeneca Symposium: The Role of Biomarkers
        in patients with metabolic syndrome.                           in Cardiovascular Disease (CVD) Risk Assessment
                                                                       Chair: Professor Andrew Tonkin
        Findings from this study have been presented both
        nationally as a student finalist oral presentation at          Professor Tonkin started the proceedings by presenting
        the High Blood Pressure Research Council 2008,                 an ‘Overview of the Global Burden of CVD’ and this was
        and internationally as an oral presentation at the             followed by Dr Paul M Ridker, Director of the Center for
        European Society of Cardiology 2009.                           Cardiovascular Disease Prevention at the Brigham and
                                                                       Women’s Hospital, Boston, and Principal Investigator
                                                                       for the recently published JUPITER Study. Dr Ridker
        Meetings and symposia                                          presented information from the JUPITER study on the
                                                                       effects of lowering high levels of CRP a protein marker
        Cardiac Society of Australia and New Zealand                   for inflammation in the blood with rosuvastatin, and the
        Sydney, 13 to 16 August, 2009                                  effect on heart attack risk.
        The Cardiac Society of Australia and New Zealand Annual
        Scientific Meeting is the major event on the Australian        Professor Stefan Blankenberg from the Department
        Cardiology calendar.                                           of Medicine, Johannes Gutenberg University, Mainz in
                                                                       Germany, presented information of the role of ‘Biomarkers
        In line with its commitment to education in therapeutics,      in Diagnostic and Risk Assessment’. These presentations
        CCRE Therapeutics continued its sponsorship of satellite       were followed by a lively discussion, chaired by Professor
        symposia at this event and, in conjunction with CSL            Tonkin, on the case for CRP in CVD risk assessment
        Biotherapies and Astra Zeneca (Australia), put together        versus the case for the multiple biomarker approach.
        an expert team of local and international speakers for
        two very interesting symposia.                                 Both Symposia brought together local and international
                                                                       experts who presented valuable information from recent
                                                                       clinical and laboratory research and offered an opportunity
                                                                       for discussion in a more intimate environment.

26 | Annual Report 2009
Financial report
CCRE Therapeutics continues to stand alone following the end of our original NHMRC CCRE infrastructure grant
of $2 million in 2007. Further success with NHMRC, NHF and ARC grants as well as industry funding has ensured
financial viability and sustainable growth.

Not appearing on the graph below is National Institute of Health (NIH) support. A successful Rapid Access to
Investigational Drugs (RAID) grant secured in-kind support of US$2.9 million. The NIH also awarded CCRE Therapeutics
US$50 million over seven years for the large-scale ASPREE study which will begin new recruitment in 2010.

                                                             Centre of Cardiovascular Research and Education in Therapeutics | 27

        NHMRC                                                            NHF

        P Davidson, P Macdonald, D Curnow, P Newton,                     DL Hare, D Clarke, H Krum
        D Leung, G Tofler, H Krum                                        The Melbourne Depression in Heart Failure
        Oxygen to relieve dyspnoea in non-hypoxaemic                     Collaborative Medication trial
        patients with end-stage heart failure                            2008–2012 $893,581 (NHF and Beyond Blue)
        2007–2009 $300,000 (Palliative Care)
                                                                         H Krum, DJ Campbell, C Reid, S Stewart
        S Stewart, P Scuffham, T Marwick, J Horowitz, H Krum,            Randomised, placebo-controlled clinical trial of
        P Davidson, P Macdonald, C Reid                                  pharmacological intervention in high risk subjects
        Which Heart failure Intervention is most Cost-effective          with elevated BNP to prevent new heart failure
        and consumer friendly in reducing Hospital care:                 2008–2009 $126,671 (Grant-in-Aid)
        The WHICH study, 2007–2011 $878,702 (Health Services)
                                                                         Reid CM, Cameron J, Kingwell B, Dart A
        J McNeil, A Tonkin, L Beilin, C Reid, H Krum, M Nelson           Independent and combined effects of blood pressure
        ASPirin in Reducing Events in the Elderly (ASPREE)               lowering and lipid lowering on vascular stiffness
        2005–2009 $3,503,500 (Project)                                   2008–2009 $120,126 (Grant-in-Aid)

        H Krum, D Kelly, S Itescu                                        A Owen, C Reid, P McLennan, H Krum
        Novel therapeutic strategies to reduce the burden                Omega-3 fatty acid status and cardiovascular risk
        of chronic heart failure                                         in older Australians
        2005–2009 $4,634,965 (Program)                                   2009–2010 $130,800 (Grant-in-Aid)

        J Simes, D Ghersi, M Stockler, T Keech, S Green,                 ARC Linkage Grant
        D Henderson-Smart, H Krum, G Jennings
        A National Clinical Trials Register                              D Liew, C Reid, A Owen, J Shaw, D Magliano
        2005–2010 $1,500,000 (Enabling)                                  Epidemiological modelling of cardiovascular disease
                                                                         and diabetes in Australia
        R Buchbinder, L March, M Lassaire, C Reid                        2007–2009 $212,000
        The Australian Rheumatology Association Database (ARAD)
        2006–2010 $1,250,000 (Enabling)                                  Industry

        Nelson MR, Reid CM, Ryan P, Tonkin AM, Wing LMH                  BMS
        Absolute risk prediction of subsequent cardiovascular            Integrate Project
        events in elderly Australian with hypertension                   2007–2009 $389,499
        2008–2009 $192,000
        (General Practice Clinical Research Program)                     Glaxo Wellcome Australia
                                                                         H Krum, A Kompa
        CM Reid                                                          Therapeutic Efficacy of Soluable Epoxide Hydrolase
        Senior Research Fellowship                                       Inhibition in a Post-MI model of Cardiac Remodelling
        2008–2012 $537,500                                               2009 $108,081

        Budge M, Storey E, Tonkin AM, Wong T, Reid CM, Ames D            Pfizer (CVL Grant)
        Aspirin for the prevention of cognitive decline in the Elderly   M McGrady, H Krum
        (EnVISION)                                                       The prevalence of heart failure in Aboriginal
        2008–2012 $1,271,102                                             communities in Central Australia
                                                                         2009 $55,000
        J McNeil, C Reid, H Krum, A Tonkin, R Woods
        Mobile Assessment Centre and blood                               GlaxoSmithKline Australia Pty Ltd
        processing laboratory                                            H Krum
        2009 $90,000 (Equipment)                                         A Clinical Outcomes Study of Darapladib versus Placebo
                                                                         in Subjects with Chronic Coronary Heart Disease to
        H Krum, P Scammells, B Wang                                      Compare the Incidence of Major Adverse Cardiovascular
        Development of novel anti-inflammatory compounds                 Events (MACE) – STABILITY Trial
        2009 $196,250 (Development)                                      2009–2010 $219,600

28 | Annual Report 2009
National Institute of Health (USA)

Rapid Access to Investigational Drugs (RAID)
R Gilbert, D Kelly, H Krum, S Williams
Treatment of Diabetic Nephropathy Using
a Purpose-Designed Anti-Fibrotic Drug
2008–2010 US$2,900,000 (in-kind support)

R Grimm, J McNeil, A Tonkin, C Reid,
M Nelson, R Woods
ASPirin in Reducing Events in the Elderly (ASPREE)
2009–2015 US$50,445,006


Collaborative Research Initiative Grant
F Ierino, N Isbel, H Krum
A randomised controlled trial of the beta-blocker carvedilol
versus placebo to reduce cardiovascular morbidity and
mortality in patients receiving dialysis
2008–2010 $704,400


C Reid, A Ajani, B Billah, A Brennan, D Dinh,
A Hannaford, H Krum, J McNeil, G Shardey, A Tonkin
Testing and validating draft ‘Operating Principles and
Technical Standards for Australian Clinical Quality Registries
2008–2009 $931,686

                                                                 Centre of Cardiovascular Research and Education in Therapeutics | 29

        Ritz E, Krum H, Schlaich M, Whitbourn R, Sobotka PA,            Leet A, Richardson M, Senior JA, Funston R, Skiba M,
        Sadowski J, Bartus K, Kapelak B, Walton A, Sievert H,           Bailey M, Krum H. A bioavailability study of cyclosporine:
        Thambar S, Abraham WT, Esler M, Wang Y, Tsun Z,                 comparison of Neoral versus Cysporin in stable heart
        Machnik A, Neuhofer W, Jantsch J, Dahlmann A, Tammela T,        transplant recipients. J Heart Lung Transplant.
        Machura K, Park JK, Beck FX, Müller DN, Derer W, Goss J,        2009 Sep; 28(9):894–8.
        Ziomber A, Dietsch P, Wagner H, van Rooijen N, Kurtz A,
        Hilgers KF, Alitalo K, Eckardt KU, Luft FC, Kerjaschki D,       Rasmussen HH, Figtree GA, Krum H, Bundgaard H.
        Titze J. New approaches to pathogenesis and                     The use of beta3-adrenergic receptor agonists in the
        management of hypertension. Clin J Am Soc Nephrol.              treatment of heart failure. Curr Opin Investig Drugs.
        2009 Dec;4(12):1886–91.                                         2009 Sep;10(9):955–62.

        Krum H. Optimising management of chronic heart failure.         Schlaich MP, Sobotka PA, Krum H, Lambert E, Esler MD.
        Lancet 2009 Nov 28;374(9704):1808–1809. (invited editorial)     Renal sympathetic-nerve ablation for uncontrolled
                                                                        hypertension. N Engl J Med. 2009 Aug 27;
        Zammit SC, Cox AJ, Gow RM, Zhang Y, Gilbert RE, Krum H,         361(9):932–4. (letter)
        Kelly DJ, Williams SJ. Evaluation and optimization of
        antifibrotic activity of cinnamoyl anthranilates.               Gheorghiade M, Khan S, Blair JE, Harinstein ME, Krum H,
        Bioorg Med Chem. 2009 Dec 15;19(24):7003–6.                     Mukherjee R, Pitt B; Eplerenone Post-Acute Myocardial
                                                                        Infarction Heart Failure Efficacy and Survival (EPHESUS)
        Chan CC, Reid CM, Aw TJ, Liew D, Haas SJ, Krum H.               Investigators. The effects of eplerenone on length of stay
        Do COX-2 inhibitors raise blood pressure more than              and total days of heart failure hospitalization after myocardial
        nonselective NSAIDs and placebo? An updated meta-               infarction in patients with left ventricular systolic
        analysis. J Hypertens, 2009;Dec 27(12):2332–2341.               dysfunction. Am Heart J. 2009 Sep;158(3):437–43.

        Thom O, Taylor DM, Wolfe RE, Cade J, Myles P, Krum H,           Ezekowitz JA, Hernandez AF, Starling RC, Yancy CW,
        Wolfe R. Comparison of a supra-sternal cardiac output           Massie B, Hill JA, Krum H, Diaz R, Ponikowski P, Metra M,
        monitor (USCOM) with the pulmonary artery catheter.             Howlett JG, Gennevois D, O’Connor CM, Califf RM,
        Br J Anaesth. 2009 Dec;103(6):800–4.                            Fonarow GC. Standardizing care for acute decompensated
                                                                        heart failure in a large megatrial: The approach for the
        Kotecha D, Flather M, McGrady M, Pepper J, New G,               Acute Studies of Clinical Effectiveness of Nesiritide in
        Krum H, Eccleston D. Contemporary predictors                    Subjects with Decompensated Heart Failure
        of coronary artery disease in patients referred for             (ASCEND-HF). Am Heart J, 2009;157:219–228.
        angiography. Eur J Cardiovasc Prev Rehabil.
        2009 Oct 24. [Epub ahead of print]                              Krum H. Consider beta blockers for patients with heart
                                                                        failure. BMJ, 2009;338:1384–1385.
        Schlaich MP, Sobotka PA, Krum H, Whitbourn R, Walton A,
        Esler MD. Renal Denervation as a Therapeutic Approach           Krum H, Iyngkaran P, Lekawanvijit S. Pharmacologic
        for Hypertension: Novel Implications for an                     management of the cardiorenal syndrome in heart failure.
        Old Concept. Hypertension, 2009 Dec;54(6):1195–1201.            Current Heart Failure Reports, 2009;6:105–111.

        Kemp W, Kompa A, Phrommintikul A, Herath C, Zhiyuan J,          Krum H, Sanders P. Expanding indications for pacing
        Angus P, McLean C, Roberts S, Krum H. Urotensin II              in chronic heart failure. MJA, 2009; 190;470–471.
        modulates hepatic fibrosis and portal hemodynamic               (invited editorial)
        alterations in rats. Am J Physiol Gastrointest Liver Physiol.
        2009 Oct;297(4):G762–7.                                         Martin JH, Connelly KA, Boyle A, Kompa A, Zhang Y, Kelly D,
                                                                        Gilbert RE, Krum H. Effect of atorvastatin on cardiac
        Weber MA, Black H, Bakris G, Krum H, Linas S, Weiss R,          remodelling and mortality in rats following hyperglycemia
        Linseman JV, Wiens BL, Warren MS, Lindholm LH.                  and myocardial infarction. Int J Card, 2009 April 21.
        A selective endothelin-receptor antagonist to reduce blood      [Epub ahead of print]
        pressure in patients with treatment-resistant hypertension:
        a randomised, double-blind, placebo-controlled trial.           Connelly KA, Kelly DJ, Zhang Y, Prior DL, Advani A, Cox AJ,
        Lancet, 2009 Oct 24;374(9699):1423–31.                          Thai K, Krum H, Gilbert RE. Inhibition of protein kinase C-ß
                                                                        by ruboxistaurin preserves cardiac function and reduces
                                                                        extracellular matrix production in diabetic cardiomyopathy.
                                                                        Circ Heart Fail, 2009;2:129–137.

30 | Annual Report 2009
Krum H, Swergold G, Curtis SP, Kaur A, Wang H,                 Reid CM, Ajani AE, Eccleston D. Why we need
Smugar SS, Weir MR, Laine L, Brater DC, Cannon CP.             a national registry in interventional cardiology.
Factors associated with blood pressure changes in              Med J Aust. 2009 Feb 2;190(3):162–3.
patients receiving diclofenac or etoricoxib: results from
the MEDAL study. J Hypertension, 2009;27:886–893.              Joubert J, Reid C, Barton D, Cumming T, McLean A,
                                                               Joubert L, Barlow J, Ames D, Davis S. Integrated care
Krum H, Schlaich M, Whitbourn R, Sobotka PA, Sadowski          improves risk-factor modification after stroke: initial results
J, Bartus K, Kapelak B,Walton A, Sievert H, Thambar S,         of the Integrated Care for the Reduction of Secondary
Abraham WT, Esler M. Catheter-based renal sympathetic          Stroke model. J Neurol Neurosurg Psychiatry. 2009
denervation for resistant hypertension: a multicentre safety   Mar;80(3):279–84.
and proof-of-principle cohort study. Lancet,
2009;373:1275–1281.                                            Reid C, Billah B, Dinh DT, Skillington PD, Smith JA,
                                                               Yii M, Seevanayagam S, Pick A, Mohajeri M, Shardey GC.
Krum H, Curtis SP, Kaur A, Wang H, Smugar SS, Weir MR,         An Australian Risk Prediction Model for 30-day Mortality
Laine L, Brater DC, Cannon CP. Baseline factors                after Isolated Coronary Artery Bypass – the AusSCORE.
associated with congestive heart failure in patients           J Thorac Cardiovasc Surg, 2009; 138: 904–10.
receiving etoricoxib or diclofenac: multivariate analysis
of the MEDAL program. Eur J Heart Fail, 2009; Jun              Yap CH, Yan BP, Akowuah E, Dinh DT, Smith JA,
11(6):542–50.                                                  Shardey GC, Tatoulis J, Skillington PD, Newcomb A,
                                                               Mohajeri M, Pick A, Seevanayagam S, Reid CM. Does prior
Becker MC, Wang TH, Wisniewski L, Wolski K, Libby P,           percutaneous coronary intervention adversely affect early
Luscher TF, Borer JS, Mascette AM, Husni ME, Solomon DH,       and mid-term survival after coronary artery surgery?
Graham DY, Yeomans ND, Krum H, Ruschitzka F, Lincoff AM,       JACC Cardiovasc Interv, 2009; 8:758–64.
Nissen SE for the PRECISION Investigators. Rationale,
design, and governance of Prospective Randomized               Owen AJ, Retegan C, Rockell M, Jennings G, Reid CM.
Evaluation of Celecoxib Integrated Safety versus Ibuprofen     Inertia or inaction? Blood pressure management and
Or Naproxen (PRECISION), a cardiovascular end point trial      cardiovascular risk in diabetes. Clin Exp Pharmacol
of nonsteroidal anti-inflammatory agents in patients with      Physiol. 2009 Jul;36(7):643–7.
arthritis. Am Heart J, 2009;157:606–12.
                                                               Walls HL, Peeters A, Son PT, Quang NN, Hoai NT, Loi do D,
McGrady M, Krum H. Screening: the new frontier in heart        Viet NL, Khai PG, Reid CM. Prevalence of underweight,
failure management. Cardiovasc Ther. 2009;27(1):1–3.           overweight and obesity in urban Hanoi, Vietnam.
                                                               Asia Pac J Clin Nutr. 2009;18(2):234–9.
Schneider H, Lam L, Lokuge A, Krum H,
Naughton MT, Smit P, Bystrzycki A, Eccleston D,                Cowan BR, Young AA, Anderson C, Doughty RN,
Federman J, Flannery G, Cameron P. B-type natriuretic          Krittayaphong R, Lonn E, Marwick TH, Reid CM,
peptide testing, clinical outcomes, and health services        Sanderson JE, Schmieder RE, Teo K, Wadham AK,
use in emergency department patients with dyspnea.             Worthley SG, Yu CM, Yusuf S, Jennings GL.
Ann Intern Med, 2009;150:365–371.                              The cardiac MRI substudy to ongoing telmisartan alone
                                                               and in combination with ramipril global endpoint trial/
Krum H, Abraham WT. Heart failure. Lancet,                     telmisartan randomized assessment study in ACE-
2009;373:941–955. (invited review)                             intolerant subjects with cardiovascular disease: analysis
                                                               protocol and baseline characteristics. Clin Res Cardiol.
Kemp W, Colman J, Thompson K, Madan A, Vincent M,              2009 Jul;98(7):421–33.
Chin-Dusting J, Kompa A, Krum H, Roberts S.
Norfloxacin treatment for clinically significant portal        Cowan BR, Young AA, Anderson C, Doughty RN,
hypertension: results of a randomised double-blind             Krittayaphong R, Lonn E, Marwick TH, Reid CM,
placebo-controlled crossover trial. Liver International,       Sanderson JE, Schmieder RE, Teo K, Wadham AK,
2009;29(3):427–433.                                            Worthley SG, Yu CM, Yusuf S, Jennings GL; ONTARGET
                                                               Investigators. Left ventricular mass and volume with
Brady SR, de Courten B, Reid CM, Cicuttini FM,                 telmisartan, ramipril, or combination in patients with
de Courten MP, Liew D. The role of traditional                 previous atherosclerotic events or with diabetes mellitus
cardiovascular risk factors among patients with                (from the ONgoing Telmisartan Alone and in Combination
rheumatoid arthritis. J Rheumatol. 2009 Jan;36(1):34–40.       With Ramipril Global Endpoint Trial [ONTARGET]).
                                                               Am J Cardiol. 2009 Dec 1;104(11):1484–9.

                                                                Centre of Cardiovascular Research and Education in Therapeutics | 31
        Briggs AM, March L, Lassere M, Reid C, Henderson L,           Freeman M, Clark D, Andrianopoulos N, Duffy S, Lim H,
        Murphy B, van den Haak R, Rischin A, Staples M,               Brennan A, Charter K, Shaw J, Horrigan M, Ajani A,
        Buchbinder R. Baseline Comorbidities in a Population-         Sebastain M, Reid C, Farouque O. Procedural and clinical
        Based Cohort of Rheumatoid Arthritis Patients Receiving       outcomes of percutaneous coronary intervention for ostial
        Biological Therapy: Data from the Australian Rheumatology     lesions in proximal coronary arteries. Catheterization and
        Association Database. Int J Rheumatol. 2009;                  Cardiovascular Intervention, 2009;73:763–768.
        Epub ahead of print.
                                                                      Butler MJ, Eccleston D, Ajani A, Lefkovits J, Clark DJ,
        Ademi Z, Liew D, Chew D, Conner G, Shiel L, Nelson M,         Andrianopoulos N, Brennan A, Reid CM, Farrington C,
        Soman A, Steg G, Bhatt DL, Reid C; REACH registry             Walton AS, Dart AM, Duffy SJ, on behalf of the Melbourne
        investigators. Drug treatment and cost of cardiovascular      Interventional Group (MIG). The effect of intended duration
        disease in Australia. Cardiovasc Ther. 2009 Fall;27(3):       of clopidogrel use on early and late mortality and major
        164–72.                                                       adverse cardiac events in patients with drug-eluting stents.
                                                                      American Heart Journal. 2009;157(5):899–907.
        Brasacchio D, Dinh DT, Billah B, Shardey G, Reid CM
        on behalf of the Australian Society of Cardiac and Thoracic   Yap C-H, Andrianopoulos N, Dinh DT, Billah B, Rosalion AM,
        Surgeons Database Project Steering Committee. Cardiac         Reid CM. Short and mid-term outcomes of coronary
        Surgery in Victorian Public Hospitals 2007–2008: Hospital     artery bypass surgery performed by surgeons in training.
        Report. Quality and Safety Branch, Department of Human        The Journal of Thoracic and Cardiovascular Surgery.
        Services, Melbourne, Victoria 2009.                           2009;137:1088–1092.

        Brasacchio D, Dinh DT, Billah B, Shardey G, Reid CM           Yan BP, Clark DJ, Buxton B, Ajani AE, Smith JA, Duffy SJ,
        on behalf of the Australian Society of Cardiac and Thoracic   Shardey GC, Skillington PD, Farouque O, Yii M, Yap C-H,
        Surgeons Database Project Steering Committee.                 Andrianopoulos N, Brennan A, Dinh D, Reid CM, on
        Cardiac Surgery in Victorian Public Hospitals 2007–2008:      behalf of the Australasian Society of Cardiac and Thoracic
        Report to the Public. Quality and Safety Branch,              Surgeons (ASCTS) and the Melbourne Interventional
        Department of Human Services, Melbourne VIC 2009.             Group (MIG). Clinical characteristics and early mortality
                                                                      of patients undergoing coronary artery bypass grafting
        Brasacchio D, Dinh DT, Billah B, Shardey G, Reid CM           compared to percutaneous coronary intervention: Insights
        on behalf of the Australian Society of Cardiac and            from the Australasian Society of Cardiac and Thoracic
        Thoracic Surgeons Database Project Steering Committee.        Surgeons (ASCTS) and the Melbourne Interventional
        Cardiac Surgery in Australian Hospitals 2007–2008:            Group (MIG) registries. Heart Lung and Circulation.
        National Report. Melbourne VIC 2009.                          2009;18(3):184–90.

        Dinh DT, Di Giambattista K, Billah B, Shardey G,              Zwahlen D, Andrianopoulos N, Matheson B, Duchesne G,
        Reid CM on behalf of the Australian Society of Cardiac        Millar J. High-Dose-Rate brachytherapy in combination
        and Thoracic Surgeons Database Project Steering               with conformal external beam radiotherapy in the
        Committee. Cardiac Surgery in NSW Public Hospitals            treatment of prostate cancer. Brachytherapy.
        2007–2008: NSW Service Report. Greater Metropolitan           2009;9(1):27–35.
        Clinical Taskforce, NSW Health, Melbourne VIC 2009.
                                                                      Yap CH, Sposato L, Akowuah E, Theodore S, Dinh DT,
        Gurvitch R, Lefkovits J, Warren RJ, Duffy SJ, Clark DJ,       Shardey GC, Skillington PD, Tatoulis J, Yii M, Smith JA,
        Eccleston D, Yan BP, Reid C, Brennan A, Andrianopoulos        Mohajeri M, Pick A, Seevanayagam S, Reid CM.
        N, Ajani AE. Clinical outcomes of drug eluting stent use in   Contemporary results show repeat coronary artery
        high risk patients with ST elevation Myocardial Infarction.   bypass grafting remains a risk factor for operative
        Int J Cardiol 2009 (Epub ahead of print)                      mortality. Ann Thorac Surg, 2009; 87(5): 1386–91.

        Lim H, Farouque O, Andrianopoulos N, Yan B, Lim C,            Piercy M, McNicol L, Dinh DT, Story DA, Smith JA.
        Brennan A, Reid C, Freeman M, Charter K, Black A New G,       Major complications related to the use of transesophageal
        Ajani A, Duffy S, Clark D. Survival of elderly patients       echocardiography in cardiac surgery. J Cardiothorac Vasc
        undergoing percutaneous coronary intervention for acute       Anesth, 2009; 23(1): 62–5.
        myocardial infarction complicated by cardiogenic shock.
        Journal of American College of Cardiology Interventions,
        2009; 2:146–152.

32 | Annual Report 2009
Soderberg S, Colquhoun D, Keech A, Yallop J, Barnes E,           Ashton E, Windebank E, Skiba M, Reid C, Schneider H,
Pollicino C, Simes RJ, Tonkin A, Nestel P, for the LIPID         Rosenfeldt F, Tonkin A, Krum H. Why did high-dose
Study Investigators. Leptin but not adiponectin is a predictor   rosuvastatin not improve cardiac remodelling in chronic
of recurrent cardiovascular events in men: results from the      heart failure? Mechanistic insights from the UNIVERSE
Long-term Intervention with Pravastatin in Ischaemic             study. Int J Cardiol (in press).
Disease (LIPID) Study. Int J Obes, 2009;33:123–30.
                                                                 Stewart JI, Washbrook E, Tonkin A. Cardiovascular
Barr EL, Boyko EJ, Zimmet PZ, Wolfe R, Tonkin AM,                risk management. 4. Moderate- to low-risk patients
Shaw JE. Continuous relationships between non-diabetic           – management recommendations. Eur J Gen Practice
hyperglycaemia and cardiovascular disease and all-cause          (in press).
mortality: the AusDiab Study. Diabetologia, 2009;52:
415–424.                                                         Chen L, Tonkin AM, Moon L, Mitchell P, Dobson A, Giles G,
                                                                 Hobbs M, Phillips P, Shaw JE, Simmons D, Simons LA,
Tonkin A, Forbes A, Haas SJ. The evidence on trial:              Fitzgerald AP, De Backer G, De Bacquer D. Recalibration
Cholesterol lowering and cancer. Heart Asia, 2009;1:6–10.        and validation of the SCORE risk chart in the Australian
                                                                 population: the AusSCORE chart. Eur J Cardiovasc Prev
Barr EL, Tonkin AM, Welborn TA, Shaw JE. Validity of             Rehab (in press, accepted April 2009).
self-reported cardiovascular disease events in comparison
to medical record adjudication and a statewide hospital          Beauchamp A, Peeters A, Wolfe R, Turrell G, Harriss L,
morbidity database: the AusDiab study. Int Med J,                Giles GG, English DR, McNeil J, Magliano D, Harrap S,
2009;39:49–53.                                                   Liew D, Hunt D, Tonkin AM. Inequalities in cardiovascular
                                                                 disease mortality: the role of behavioural, physiological and
Tonkin AM, Chen L. Where on the Healthcare continuum             social risk factors. J. Epidemiology and Community Health
should we invest? The case for primary care? Heart Lung          (in press).
and Circ, 2009;18:108–113.
                                                                 Chen L, Magliano DJ, Balkau B, Colagiuri S, Zimmet PZ,
Tonkin AM, Boyden AN, Colagiuri S. Maximising the                Tonkin AM, Shaw JE. An Australian diabetes risk
effectiveness and cost-effectiveness of cardiovascular           assessment tool based on demographic, lifestyle and
disease prevention in the general population.                    simple anthropometric measures. Med J Aust (in press).
Med J Aust, 2009;191:300–302.
                                                                 Barr EL, Cameron AJ, Balkau B, Zimmet PZ, Welborn T,
Cameron AJ, Dunstan DW, Owen N, Zimmet PZ, Barr                  Tonkin AM, Shaw JE. HOMA insulin sensitivity index,
ELM, Tonkin AM, Magliano D, Murray SG, Welborn TA,               hyperglycaemia and the risk of all-cause mortality and
Shaw JE. Health and mortality consequences of                    cardiovascular disease in the general population
abdominal obesity: evidence from the AusDiab study.              – the AusDiab study. Diabetologia (in press).
Med J Aust, 2009;191:202–208.
                                                                 Dennekamp M, Akram M, Abramson MJ, Tonkin AM,
Tonkin AM, Beauchamp A, Stevenson CN.                            Sim MR, Fridman M, Erbas B. The role of outdoor air
The importance of extinguishing secondhand smoke.                pollution as a trigger for an out-of-hospital cardiac arrests.
Circulation, 2009;120:1339–1341.                                 Epidemiology (in press).

Cui J, Forbes A, Kirby A, Simes J, Tonkin A.                     Cameron AJ, Sicree RA, Zimmet PZ, Albert KGMM,
Laboratory and non-laboratory based risk prediction              Tonkin AM, Balkau B, Tuomilhto J, Chitson P, Shaw JE.
models for secondary prevention of cardiovascular                Cutpoints for abnormal waist circumference in Europids
disease: the LIPID study. Eur J Cardiovasc Prev Rehabil,         and South Asians: An evaluation of methods and
2009;16:660–668.                                                 re-assessment of association with incident Type 2
                                                                 diabetes. Obesity (in press).
Driscoll A, Worrall-Carter L, Hare DL, Davidson PM,
Riegel B, Tonkin A, Stewart S. Evidence-based chronic            Rostambeigi N, Tonkin A, Atkins R, Ghanbarian A,
heart failure management programs: reality or myth?              Cameron A, Forbes A, Momenan AA, Hadaegh F,
Qual Saf Health Care, 2009; 18: 450–5.                           Mirmiran P, Zimmet P, Azizi F, Shaw J. Waist circumference
                                                                 has heterogenous impact on the metabolic syndrome
                                                                 related outcomes in different ethnicities. Diabetes Res
                                                                 Clin Prac (in press).

                                                                  Centre of Cardiovascular Research and Education in Therapeutics | 33
        Kritharides L, Brown A, Jeremy R, Tonkin A, Walsh W,            Thrift AG, Dewey HM, Sturm JW, Srikanth VK, Gilligan AK,
        White H. Overview and determinants of CV disease                Gall SL, Macdonnell RAL, McNeil JJ, Donnan GA.
        in Indigenous populations. Heart Lung and Circulation           Incidence of Stroke Subtypes in the North East Melbourne
        (in press).                                                     Stroke Incidence Study (NEMESIS): Differences between
                                                                        Men and Women. Neuroepidemiology, 2009;32(1):11–18.
        Curtis AJ, Stoelwinder JU, McNeil JJ.
        Management of waiting lists needs sound data.                   Walls HL, McNeil JJ, Peeters A. Population Versus
        Med J Australia, 2009;191(8):423–424.                           High-risk Interventions for Obesity. Epidemiology,
        Evans SM, Cameron PA, McNeil JJ.
        Reforming NSW Health: the importance of using                   Walls H, Wolfe R, Haby M, Magliano D, de Courten M,
        credible data. Med J Aust, 2009;190(9):515.                     Reid C, McNeil JJ, Shaw, J. Trends in BMI of Urban
                                                                        Australian Adults, 1980–2000. Public Health Nutr.
        Gabbe BJ, Bailey M, Cook JL, Makdissi M, Scase E,               2009;22:1–8 (Epub ahead of print).
        Ames N, Wood T, McNeil JJ, Orchard JW. The association
        between hip and groin injuries in the elite junior football     Myles PS. What’s new in trial design: propensity scores,
        years and injuries sustained during elite senior competition.   equivalence, and non-inferiority. J Extra Corpor Technol.
        Br J Sports Med, 2009; [Epub ahead of print].                   2009 Dec;41(4):P6–10.

        Haller G, Stoelwinder J, Myles P, McNeil JJ:                    Leslie K, Myles PS, Forbes A, Chan MT. The Effect
        Quality and Safety indicators in Anesthesia:                    of Bispectral Index Monitoring on Long-Term Survival
        Anesthesiology, 2009;110(5):1158–1175.                          in the B-Aware Trial. Anesth Analg. 2009 Nov 12
                                                                        (Epub ahead of print).
        Lowthian JA, Diug BO, Evans SM, Maxwell EL, Street AM,
        Piterman L, McNeil JJ. Who is responsible for the care          Leslie K, Chan MT, Myles PS, Forbes A, McCulloch TJ.
        of patients treated with warfarin therapy? Med J Aust,          Posttraumatic Stress Disorder in Aware Patients from
        2009;190(12):674–677.                                           the B-Aware Trial. Anesth Analg. 2009 Oct 27
                                                                        (Epub ahead of print).
        Ngo DT, Sverdlov AL, McNeil JJ, Horowitz JD.
        Correlates of arterial stiffness in an ageing population:       Haller G, Myles PS, Taffé P, Perneger TV, Wu CL.
        role of asymmetric dimethylarginine. Pharmacol Res.             Rate of undesirable events at beginning of academic year:
        2009;60(6):503–507.                                             retrospective cohort study. BMJ. 2009 Oct 13;339:b3974.

        Ngo DT, Sverdlov AL, Willoughby SR, Nightingale AK              Story DA, Fink M, Leslie K, Myles PS, Yap SJ, Beavis V,
        Chirkov YY, McNeil JJ, Horowitz JD. Determinants of             Kerridge RK, McNicol PL. Perioperative mortality risk score
        occurrence of aortic sclerosis in an aging population.          using pre- and postoperative risk factors in older patients.
        JACC Cardiovasc Imaging, 2009;2(8):919–927.                     Anaesth Intensive Care. 2009 May;37(3):392–8.

        Nichol AD, Cooper DJ. POLAR Study Investigators on              Todd MM, Hindman BJ, Clarke WR, Torner JC, Weeks JB,
        behalf of the ANZICS-Clinical Trials Group; EPO Study           Bayman EO, Shi Q, Spofford CM; IHAST Investigators.
        Investigators on behalf of the ANZICS-Clinical Trials Group.    Perioperative fever and outcome in surgical patients with
        Can we improve neurological outcomes in severe                  aneurysmal subarachnoid hemorrhage. Neurosurgery.
        traumatic brain injury? Something old (early prophylactic       2009 May;64(5):897–908.
        hypothermia) and something new (erythropoietin).
        Injury, 2009;40(5):471–478.                                     Haller G, Stoelwinder J, Myles PS, McNeil J. Quality
                                                                        and safety indicators in anesthesia: a systematic review.
        Polizzotto MN, Phillips LE, Cannell P, Cohney S, Davies C,      Anesthesiology. 2009 May;110(5):1158–75.
        Opat SS, McNeil JJ, Wood EM. The Thrombotic
        thrombocytopenic purpura registry: a new national               Myles PS, Daly D, Silvers A, Cairo S. Prediction of
        resource to inform patient care and medical research.           neurological outcome using bispectral index monitoring
        Internal Medicine Journal, 2009;39(1):72–73.                    in patients with severe ischemic-hypoxic brain injury
                                                                        undergoing emergency surgery. Anesthesiology.
        Ronaldson KJ, McNeil JJ. Improving drug safety by               2009 May;110(5):1106–15.
        locating genetic markers for hypersensitivity reactions.
        Med J Aust, 2009;190(11):641–643.

34 | Annual Report 2009
Myles PR, Hubbard RB, McKeever TM, Pogson Z, Smith CJ,        Myles PS, Leslie K, Peyton P, Paech M, Forbes A,
Gibson JE. Risk of community-acquired pneumonia and           Chan MT, Sessler D, Devereaux PJ, Silbert BS, Jamrozik
the use of statins, ace inhibitors and gastric acid           K, Beattie S, Badner N, Tomlinson J, Wallace S. Nitrous
suppressants: a population-based case-control study.          oxide and perioperative cardiac morbidity (ENIGMA-II)
Pharmacoepidemiol Drug Saf. 2009 Apr;18(4):269–75.            Trial: rationale and design. ANZCA Trials Group.
                                                              Am Heart J. 2009 Mar;157(3):488–494.e1.
Buchanan FF, Myles PS, Cicuttini F. Patient sex and its
influence on general anaesthesia. Anaesth Intensive Care.     Story DA, Fink M, Leslie K, Myles PS, Yap SJ, Beavis V,
2009 Mar;37(2):207–18. Review. PubMed PMID:                   Kerridge RK, McNicol PL. Perioperative mortality risk score
19400484.                                                     using pre- and postoperative risk factors in older patients.
                                                              Anaesth Intensive Care, 2009 May;37(3):392–8.
Myles PS. Bispectral index monitoring in ischemic-hypoxic
brain injury. J Extra Corpor Technol. 2009 Mar;41(1):P15–9.   Ramchandra R, Hood SG, Denton DA, Woods RL,
                                                              McKinley MJ, McAllen RM, May CN. Basis for the
Myles PS, Leslie K, Peyton P, Paech M, Forbes A,              preferential activation of cardiac sympathetic nerve activity
Chan MT, Sessler D, Devereaux PJ, Silbert BS,                 in heart failure. Proceedings of the National Academy of
Jamrozik K, Beattie S, Badner N, Tomlinson J, Wallace S;      Science USA, 2009;106(3):924–928.
ANZCA Trials Group. Nitrous oxide and perioperative
cardiac morbidity (ENIGMA-II) Trial: rationale and design.    Woods RL, Tonkin AM, Nelson MR, Reid CM. Should
Am Heart J. 2009 Mar;157(3):488–494.e1.                       aspirin be used for the primary prevention of cardiovascular
                                                              disease in people with diabetes [editorial]? Medical Journal
Silbert BS, Myles PS. Is fast-track cardiac anesthesia        of Australia, 2009;190:614–615.
now the global standard of care? Anesth Analg. 2009
Mar;108(3):689–91.                                            Woods RL, Nelson MR, Tonkin AM, Reid CM. In reply:
                                                              Should aspirin be used for the primary prevention of
Pasternak JJ, McGregor DG, Lanier WL, Schroeder DR,           cardiovascular disease in people with diabetes [editorial]?
Rusy DA, Hindman B, Clarke W, Torner J, Todd MM;              Medical Journal of Australia, 2009;191(6):356–357.
IHAST Investigators. Effect of nitrous oxide use on
long-term neurologic and neuropsychological outcome           Driscoll A, Davidson P, Clark R, Huang N and Aho Z
in patients who received temporary proximal artery            on behalf of National Heart Foundation consumer
occlusion during cerebral aneurysm clipping surgery.          resource working group. Tailoring Consumer Resources
Anesthesiology. 2009 Mar;110(3):563–73.                       To Enhance Self-Care In Chronic Heart Failure.
                                                              Australian Critical Care Journal, 2009;22:133–140.
Daly DJ, Myles PS. Update on the role of paravertebral
blocks for thoracic surgery: are they worth it?               Cameron J, Worrall-Carter L, Driscoll A, and Stewart S.
Curr Opin Anaesthesiol. 2009 Feb;22(1):38–43.                 Measuring self-care in chronic heart failure: a review
                                                              of the psychometric properties of clinical instruments.
McIlroy DR, Myles PS, Phillips LE, Smith JA.                  Journal of Cardiovascular Nursing, 2009;24(6):10–22.
Antifibrinolytics in cardiac surgical patients receiving
aspirin: a systematic review and meta-analysis.               Clark RA, Driscoll A, Davidson PM. Access and quality
Br J Anaesth. 2009 Feb;102(2):168–78.                         of Heart Failure Management Programs in Australia.
                                                              Australian Critical Care Journal, 2009; 22:111–116.
Wallace S, Myles P. 2009 Solving the challenges
of large multicenter trials in Anesthesia. 26th Aug HSR.      Lee C, Riegel B, Driscoll A, Suwanno J, Moser DK,
PROCEEDINGS.                                                  Lennie TA, Dickson VV, Cameron J, Worrall-Carter L.
                                                              Gender Differences in Heart Failure Self-Care: A
Leslie K, Myles PS, Forbes A, Chan MT. The Effect             Multinational Cross-Sectional Study. International
of Bispectral Index Monitoring on Long-Term Survival          Journal of Nursing Studies 2009;46:1485–1495.
in the B-Aware Trial. Anesth Analg. 2009 Nov 12.
                                                              Riegel B, Driscoll A, Suwanno J, Moser D, Dickson VV,
Leslie K, Chan MT, Myles PS, Forbes A, McCulloch TJ.          Carlson B, Cameron J. An International Perspective on
Posttraumatic Stress Disorder in Aware Patients from          Heart Failure Self-Care. Journal of Cardiac Failure,
the B-Aware Trial. Anesth Analg. 2009 Oct 27.                 2009;15(6):508–516.

                                                               Centre of Cardiovascular Research and Education in Therapeutics | 35
        Tonkin A (ed.).Therapeutic Strategies in Lipid Disorders.
        Clinical Publishing, Oxford, 2009

        Book chapters
        Haas SJ, Thien F, Tonkin AM, Kong DCM, Nelson MR,
        Demos L, Zimmet H, Krum H, Liew D, McNeil JJ.
        Clozapine-associated myocarditis and cardiomyopathy
        – It’s the heart that is important, not the classification.
        In: P.H. Bruno and M.T. Giordano (editors).
        Cardiomyopathies: Effects, Causes and Treatments;
        Nova Science Publishers, Inc: Nova Biomedical Books,
        2009 pp251–283.

        Chen L, Tonkin AM. Absolute risk assessment in
        the general population. In: Tonkin A (ed.) Therapeutic
        Strategies in Lipid Disorders. Clinical Publishing,
        Oxford 2009.

        Tonkin A. The expanded evidence base and translation
        to improved outcomes. In: Tonkin A (ed.) Therapeutic
        Strategies in Lipid Disorders. Clinical Publishing,
        Oxford 2009.

36 | Annual Report 2009
Centre of Cardiovascular Research and Education in Therapeutics | 37
Centre of Cardiovascular Research and Education in Therapeutics
Department of Epidemiology and Preventive Medicine
School of Public Health and Preventive Medicine
Monash University
Level 6, The Alfred Centre
99 Commercial Road
Melbourne, Victoria 3004

Telephone:      +61 3 9903 0048
Fax:            +61 3 9903 0556
Email:          ccre@med.monash.edu.au
Website:        www.ccretherapeutics.org.au

Disclaimer: The information in this report was correct at the time of publication. Monash University reserves the right to alter this information should the need arise.
CRICOS provider: Monash University 00008C. May 2010. TSG262339

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