Cardiovascular disease and drug safety – clinical trials and pharmacoepidemiology
Medicines Monitoring Unit (MEMO)
Division of Molecular & Clinical Medicine
School of Medicine
Ninewells Hospital and Medical School
+(44) 01382 383119
Dr Isla Mackenzie MBChB (Honours) PhD FRCP Edin is a Clinical Reader in Clinical Pharmacology and Honorary Consultant Physician at the University of Dundee and Ninewells Hospital, Dundee. Research interests include cardiovascular safety of drugs, clinical trials, hypertension and technology in research.
Clinical interests include general medicine, hypertension and adrenal disorders including phaeochromocytoma. Dr Mackenzie trained in Clinical Pharmacology in Cambridge prior to moving to Dundee in 2008.
Dr Mackenzie is a member of the British Hypertension Society Executive Committee, Honorary Secretary of the Scottish Society of Physicians and is Specialty Adviser in Clinical Pharmacology for Scotland.
Dr Mackenzie’s research focuses on improving cardiovascular outcomes and drug safety using a combination of large multicentre randomised clinical trials and pharmacoepidemiological approaches to answer important clinical research questions. She is also interested in clinical trial methodology and improving patient and physician engagement in clinical research. She is Chief Investigator of the ALL-HEART study (involving 200 GP sites and 5,215 patients) and Principal Investigator of several other studies including FAST and FOURIER.
Swine flu (H1N1 Influenza A) vaccine safety study – an academic post-marketing surveillance study of the safety of swine flu vaccination in the UK population. Collaboration with Drug Safety Research Unit, Southampton /University of Plymouth. (Chief Investigator).
Spironolactone and breast cancer – a pharmacoepidemiological study in the General Practice Research Database (GPRD) investigating whether there is a link between exposure to aldosterone antagonists and increased incidence of breast cancer. Collaboration with Dundee Cancer Centre. (Principal Investigator).
The Standard care versus Celecoxib Outcome Trial (SCOT) – a large multicentre streamlined safety study comparing the cardiovascular and gastrointestinal safety of celecoxib and traditional NSAIDs in patients with osteoarthritis or rheumatoid arthritis. Collaboration with Universities of Aberdeen, Edinburgh, Glasgow, Nottingham, Birmingham and Southern Denmark (Steering Committee Member).
Febuxostat versus Allopurinol Streamlined Trial (FAST) - a prospective, randomised, open-label, blinded endpoint (PROBE) clinical trial evaluating long term cardiovascular safety of febuxostat in comparison with allopurinol in patients with chronic symptomatic hyperuricaemia. (Principal Investigator and Steering Committee Member).
BHS Prevention And Treatment of Hypertension With Algorithm Based Therapy (PATHWAY) Studies – a series of three clinical trials investigating rational treatment algorithms for hypertension. Collaboration with Universities of Cambridge, Leicester, Edinburgh, Glasgow, Exeter, Manchester, Birmingham, Imperial College and St Bartholomew’s, London. (Steering Committee Member)
Hypertension due to Conn’s adenoma - the localisation of adrenal cortical adenomas by 11C-metomidate PET scanning following dexamethasone and fludrocortisone suppression. Collaboration with University of Cambridge (Co-Investigator).
Personal health monitoring through mobile devices - Collaboration with Herriot-Watt University, University of Stirling and Glasgow School of Art. (Co-Investigator).
Effervescent medications, sodium content and blood pressure - Pharmacoepidemiological study investigating the effect of chronic therapy with effervescent tablets containing high levels of sodium and risk of hypertension and cardiovascular events.
‘Get Randomised’ Campaign – methods of engaging the public in clinical research. Highly Commended entry for Ian Stevenson Prize for Public Engagement, University of Dundee, 2010.
Further Cardiovascular Outcomes Research with PCSK9 Inhibition Subjects with Elevated Risk (FOURIER) – a multicentre randomised trial of LDL-lowering in patients at high cardiovascular risk (Principal Investigator).
Allopurinol and cardiovascular outcomes in patients with ischaemic heart disease (ALL-HEART) – a prospective, randomised, open-label, blinded endpoint (PROBE) clinical trial evaluating whether Allopurinol improves cardiovascular outcomes in patients with ischaemic heart disease (Chief Investigator and Steering Committee Member).
- George J, Majeed W, Mackenzie IS, MacDonald TM, Wei L. The association of cardiovascular events with sodium-containing effervescent, dispersible and soluble medications; nested case-control study. British Medical Journal 2013; 347:f6954. doi: 10.1136/bmj.f6954 (26 Nov 2013)
- Hapca A, Jennings C, Wei L, Wilson A, MacDonald TM, Mackenzie IS. Effectiveness of newspaper advertising for patient recruitment into a clinical trial. British Journal of Clinical Pharmacology 2013 (in press).
- Mackenzie IS, Morant SV, Bloomfield GA, MacDonald TM, O’Riordan J. Incidence and prevalence of multiple sclerosis in the United Kingdom 1990-2010: A descriptive study in the General Practice Research Database. Journal of Neurology, Neurosurgery, and Psychiatry. Published Online First 19 Sept 2013 doi:10.1136/jnnp-2013-305450.
- MacDonald TM, Mackenzie IS, Wei L, Hawkey CJ, Ford I. Methodology of a large prospective randomised open, blinded endpoint streamlined safety study of celecoxib versus traditional non-steroidal anti-inflammatory drugs in patients with osteoarthritis or rheumatoid arthritis: protocol of the Standard care versus Celecoxib Outcome Trial (SCOT). BMJ Open 2013 Jan 29;3(1). doi:pii: e002295. 10.1136/bmjopen-2012-002295. Print 2013.
- Mackenzie IS, Wei L, MacDonald TM. Cardiovascular safety of lumiracoxib: a meta-analysis of randomized controlled trials in patients with osteoarthritis. European Journal of Clinical Pharmacology. 2013;69:133-141. [Epub 2012 Jun 26]. doi: 10.1007/s00228-012-1335-1.
- Wei L, MacDonald TM, Mackenzie IS. Pioglitazone and bladder cancer: a propensity score matched cohort study. British Journal of Clinical Pharmacology 2013 Jan;75(1):254-9. doi: 10.1111/j.1365-2125.2012.04325.x.
- Mackenzie IS, MacDonald TM, Thompson A, Morant S, Wei L. Spironolactone and risk of breast cancer: cohort study. British Medical Journal 2012 Jul 13;345:e4447. doi: 10.1136/bmj.e4447.
- MacDonald TM, Mackenzie IS, Wei L. 2012. Novel ways to get good trial data: the UK experience. Discussion Paper, Institute of Medicine, Washington DC. (accessed May 18, 2012).
- Rutherford D, Wei L, Mackenzie IS, MacDonald TM. The philosophy of doing observational medicines safety research. Journal of Clinical Research and Bioethics 2012; 3:131. doi:10.4172/2155-9627.1000131.
- Mackenzie IS, Wei L, Paterson K, MacDonald TM. Cluster randomised trials of prescription medicines or prescribing policy – public and general practitioner opinions in Scotland. British Journal of Clinical Pharmacology 2012 Aug;74(2):354-61. doi: 10.1111/j.1365-2125.2012.04195.x
- Burton TJ, Mackenzie IS, Balan K, Koo B, Bird N, Soloviev DV, Azizan EAB, Aigbirhio F Gurnell M, Brown MJ. Evaluation of the sensitivity and specificity of 11C-metomidate positron emission tomography (PET)-CT scanning for lateralising aldosterone secretion by Conn’s adenomas. Journal of Clinical Endocrinology and Metabolism 2012 Jan;97(1):100-9. Epub 2011 Nov 23.
- Witham MD, Ireland S, Houston JG, Gandy SJ, Waugh S, MacDonald TM, Mackenzie IS, Struthers AD. Vitamin D therapy to reduce blood pressure and left ventricular hypertrophy in resistant hypertension – a randomised controlled trial. Hypertension 2013 (in press).
- Mackenzie IS, MacDonald TM, Shakir S, Dryburgh M, Mantay BJ, McDonnell PG, Layton D. Influenza H1N1 (swine flu) vaccination: a safety surveillance study using self-reporting of serious adverse events and pregnancy outcomes. British Journal of Clinical Pharmacology 2011 (in press).
- Wei L, MacDonald TM, Mackenzie IS. Co-prescription of co-trimoxazole and spironolactone in elderly patients. BMJ 2011;343:d5656.
- Mackenzie IS, Mantay BJ, McDonnell PG, Wei L, MacDonald TM. Managing security and privacy concerns over data storage in healthcare research. Pharmacoepidemiology and Drug Safety 2011; 20(8):885-93. Epub 2011 Jun 28.
- Mackenzie IS, MacDonald TM. Hypertension in octogenarians – treatment strategies and challenges. European Cardiology 2011;7(1):15-18.
- Wei L, Mackenzie IS, Chen Y, Struthers AD, MacDonald TM. Impact of allopurinol use on urate concentration and cardiovascular outcome. British Journal of Clinical Pharmacology 2011; 71:4;600-607.
- Mackenzie IS, Coughtrie MWH, MacDonald TM, Wei L. Antiplatelet drug interactions. Journal of Internal Medicine 2010;268:516-29.
- Mackenzie IS, MacDonald TM. The challenge of managing difficult-to-control hypertension.Prescriber Journal 2010 March;21(5):47-50.
- Mackenzie IS, MacDonald TM. Treatment of osteoarthritis in hypertensive patients. Expert Opinion on Pharmacotherapy 2010 Feb;11(3):393-403.
- Mackenzie IS, Wei L, Rutherford D, Findlay EA, Saywood W, Campbell MK, MacDonald TM. Promoting public awareness of randomised clinical trials using the media: the ‘Get Randomised’ campaign. British Journal of Clinical Pharmacology 2010; 69(2):128-135.
- Mackenzie IS. European Association of Clinical Pharmacology and Therapeutics Meeting Report.IDrugs 2009; Sept 12(9):550-4.
- Cheriyan J, Burton TJ, Bradley T, Wallace SML, Maki-Petaja KM, Mackenzie IS, McEniery CM, Brown J, Wilkinson IB. The effects of urotensin II and urantide on forearm blood flow and systemic haemodynamics in humans. British Journal of Clinical Pharmacology 2009;68(4):518-523.
- Mackenzie IS, McEniery CM, Dhakam Z, Brown MJ, Cockcroft JR, Wilkinson IB. Comparison of effects of antihypertensive agents on central blood pressure and arterial stiffness in isolated systolic hypertension. Hypertension 2009;54:414-420.
Medicine, Clinical Pharmacology and Therapeutics teaching:
- Lectures, seminars, bedside teaching in Clinical Pharmacology/Therapeutics and Medicine (2000 - present)
- Marking and question writing for University of Dundee medical student examinations (2008 - present)
- Medical School Interviews, University of Dundee (2011 - present)
- Clinical Supervisor - MBPhD students (2000 - 2008)
- Clinical Pharmacology college supervisions, Cambridge (2000 - 2004)
- Clinical School Admission Interviews, University of Cambridge (2002 - 2008)
- Year 5 Theme SSC: The Science Behind Prescribing (M-5089) (2013-)
Postgraduate and multidisciplinary teaching
- MRCP (PACES) teaching, Tayside (2012 - present)
- Educational Supervisor, General Medicine (2012 - present)
- Ward-based and clinical simulator teaching, Cambridge graduate course (2006 - 2008)
- PASTEST Lecturer in Clinical Pharmacology, London (2005 - 2008)
- Bank Physician Trainer for GSK, Cambridge (2005 - 2008)
- Member of Clinical Pharmacology Training Committee, Cambridge (2000 - 2005)
- Contributor to Clinical Pharmacology section of Medical Masterclass Website, Royal College of Physicians London / Blackwell Publishing (2003 - present)
- PGCertMedEd (distance learning) – completed 2013, University of Dundee
- Team Based Learning Workshop, June 2013
- Supporting Effective Practice in Postgraduate Supervision workshop, October 2012
- New SCOTS Educational Supervision Workshop, May 2010
- Equality and Diversity Training, University of Dundee, Feb 2010. Disability, Disability in the Workplace, Diversity in Learning and Teaching, Stress in the Workplace, A Manager’s Guide to Stress
- Train the Trainers Teaching Course (2005)
Current supervision of research students
PhD students (secondary supervisor) – David Rorie, University of Dundee 2012-
Lewis McConnachie, University of Dundee 2012-
MD student (secondary supervisor) – Claudine Jennings, University of Dundee 2012-
Forthcoming invited lectures:
- Hypertension. Tayside Pharmacists’ Meeting, March 2014.
- Cardiovascular risk and rheumatological disease: The Watson Buchanan Lecture, Scottish Society of Rheumatology meeting, November 2013.
- Spironolactone – is it time to license it for hypertension in the UK? Caledonian Society of Clinical Pharmacology Meeting, Edinburgh, November 2013.
- Presenting research using posters. Dundee Research and Academic Medicine Society (DRAMS) Meeting, Dundee, October 2013.
- Phaeochromocytoma: update on genetics - Diabetes and Endocrinology Meeting, Dundee, June 2013.
- SHARP Tayside Meeting. Management of hypertension - as easy as ACD. Dundee, May 2013.
- FAST abstracts. FAST Steering Committee Meeting, Edinburgh, May 2013.
- Update on catecholamine secreting tumours. Endocrinology Meeting, Aberdeen, November 2012.
- Gout and the FAST study. Tayside Rheumatology Meeting, Dundee, October 2012.
- Use of record linkage in clinical trials. Scottish Health Informatics Programme (SHIP) Conference: Exploiting Existing Data for Health Research, St Andrews, September 2011.
- NSAID update. SCOT Steering Committee Meeting, Edinburgh, February 2011.
- Swine flu vaccination: a safety study. CMDN Research Symposium, Dundee, January 2011.
- Trial logistics and recruitment: likely challenges. FAST Steering Committee Meeting, London, December 2010.
- The Standard care versus Celecoxib Outcome Trial. UKPCRN National Team Day, Birmingham, November 2010.
- Clinical management of phaeochromocytoma. Endocrinology 2010, London, September 2010.
- Novel uses of technologies in clinical trials. Society for Clinical Trials Annual Conference, Baltimore, United States, May 2010.
- Swine flu vaccine safety study - pilot of the use of novel technologies to collect safety data. Caledonian Society of Clinical Pharmacology Annual Meeting, Glasgow, March 2010.
- Advances in catecholamine-secreting tumours. RCPE Tayside Symposium, February 2010.
- NSAIDs and cardiovascular disease. SCOT Principal Investigator Meeting, Copenhagen, Denmark, May 2009.
- Accelerated hypertension. Acute Medicine Meeting, Ninewells Hospital, April 2009.
- Phaeochromocytoma. Grand Round, Western Infirmary, Glasgow, March 2009.
- Update on NSAIDs and cardiovascular disease. SCOT Steering Committee Meeting, Edinburgh, February 2009.
- Adrenal incidentaloma. Diabetes & Endocrinology Meeting, Ninewells Hospital, February 2009.
- Keynote lecture. Cardiovascular safety of drugs: the ‘real life’ collaborative approach in Scotland. Scottish Cardiovascular Forum, Inverness, January 2009.
- Phaeochromocytoma. Endocrinology Meeting, Aberdeen Royal Infirmary, January 2009.