Dr. Isla S Mackenzie

Clinical Reader in Clinical Pharmacology & Honorary Consultant Physician

Cardiovascular disease and drug safety – clinical trials and pharmacoepidemiology

Address:

Medicines Monitoring Unit (MEMO)
Division of Molecular & Clinical Medicine
Level 7
School of Medicine
Ninewells Hospital and Medical School
Dundee
DD1 9SY

Phone Number:

+(44) 01382 383119

Email Address:

i.s.mackenzie@dundee.ac.uk

Biography

Dr Isla Mackenzie is a Clinical Reader in Clinical Pharmacology and Honorary Consultant Physician at the University of Dundee, Ninewells Hospital, Dundee. Dr Mackenzie is Deputy Director of the Medicines Monitoring Unit (MEMO) and the Hypertension Research Centre at Ninewells Hospital.  Research interests include cardiovascular safety of drugs, clinical trials, hypertension and technology in research. Clinical interests include general and acute medicine, hypertension and adrenal disorders including phaeochromocytoma. Dr Mackenzie trained in Clinical Pharmacology in Cambridge prior to moving to Dundee in 2008.

Research

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 and Principal Investigator of several other studies.

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 (>5,215 patients).

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 (>5,706 patients). UK, Denmark, Sweden.

Treatment in Morning vs Evening (TIME) study – an online randomised trial of morning versus evening dosing of antihypertensive medications and cardiovascular outcomes (>21,000 patients).

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. UK, Denmark, The Netherlands.

BHS Prevention And Treatment of Hypertension With Algorithm Based Therapy (PATHWAY) Studies – a series of 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.

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

Cohort study of the relative incidence of major cardiovascular events among patients initiating prucalopride versus a matched control comparator.

Tayside pilot of the Scottish Treatment in Early Multiple Sclerosis (STEMS) project.

Survey of Patients with Resistant Hypertension (SPIRIT).

Impact of EU label changes for systemic diclofenac products: post-referral prescribing trends.

Impact of EU label changes for hydroxyzine products: post-referral prescribing trends. 

Evaluating diuretics in normal care (EVIDENCE) – a cluster randomised evaluation of prescribing policy for hypertension.

Publications

Recent publications:

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.

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, 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.

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.

Wilkinson IB, Heagerty A, MacDonald T, McCormack T, Chapman N, Delles C, Mackenzie I, Stetson N. Navigating the shoals in hypertension: discovery and guidance. The demise of chlortalidone in the UK? British Medical Journal 2013; (Rapid Response Letter; online 12 June 2013) http://www.bmj.com/content/344/bmj.d8218/rr/649578

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

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; doi: 10.1111/bcp.12262 (26 Nov 2013)

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).

Mackenzie IS, MacDonald TM, Thompson AM, Morant S, Wei L. Spironolactone exposure prior to the index date and effects of ethnicity on study outcomes. British Medical Journal, (Rapid Response Letter; online 20 Dec 2013) http://www.bmj.com/content/345/bmj.e4447/rr/678667.

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 2014 Apr;63(4):706-12. doi: 10.1161/HYPERTENSIONAHA.113.02177. Epub 2014 Jan 13.

Jennings CG, Mackenzie IS,  Flynn R, Ford I, Nuki G, De Caterina R, Riches PL, Ralston SH, MacDonald TM on behalf of FAST study group. Uptitration of allopurinol in patients with gout. Seminars in Arthritis and Rheumatism 2014 Jan 23. pii: S0049-0172(14)00005-5. doi: 10.1016/j.semarthrit.2014.01.004. [Epub ahead of print].

Jennings CG, Houston JG, Severn A, Bell S, Mackenzie IS, MacDonald TM. Renal artery stenosis – when to screen, what to stent? Current Atherosclerosis Reports 2014 Jun;16(6):416. doi: 10.1007/s11883-014-0416-2.

George J, Majeed W, Mackenzie I, MacDonald T, Wei L. Salt in effervescent and dispersible medications: prescriber beware. Prescriber Journal 2014; 25(7):6-8.

MacDonald TM, Ford I,  Nuki G, Mackenzie IS, De Caterina R, Findlay E, Hallas J, Hawkey CJ, Ralston S, Walters M, Webster J, McMurray J, Perez Ruiz F, Jennings CG. Protocol of the Febuxostat versus Allopurinol Streamlined Trial (FAST): A large prospective, randomised, open, blinded endpoint study comparing the cardiovascular safety of allopurinol and febuxostat in the management of symptomatic hyperuricaemia. BMJ Open 2014 Jul 10;4(7):e005354. doi: 10.1136/bmjopen-2014-005354.

Jennings CG, Mackenzie IS, MacDonald TM. Review of hyperuricaemia and hypertension: a target for treatment. J Hypertension Open Access 2014; 3:164. Doi:10.4172/2167-1095.1000164.

Wei L, Mackenzie IS, MacDonald TM, George J. Cardiovascular risk associated with sodium-containing medicines. Expert Opinion on Drug Safety 2014 Nov; 13(11):1515-23. Doi 10.1517/14740338.2014.970163 Epub 2014 Oct 10.

Flynn RW, MacDonald TM, Hapca A, Mackenzie IS, Schembri S. Quantifying the real life risk profile of inhaled corticosteroids in COPD by record linkage analysis. Respiratory Research 2014 Nov 19;15:141. Doi: 10.1186/s12931-014-0141-y.

Rorie D, Flynn R, McConnachie L, Mackenzie IS, MacDonald TM. Poster advertisements in practice waiting rooms to recruit patients to the treatment in the morning versus evening (TIME) online study. British Journal of Clinical Pharmacology 2015; doi: 10.1186/s13063-015-0582-8. (Letter)

Jennings CG, MacDonald TM, Wei L, Brown MJ, McConnachie L, Mackenzie IS. Does offering an incentive payment improve recruitment to clinical trials and increase the proportion of socially deprived and elderly participants? Trials 2015;16:80 DOI: 10.1186/s13063-015-0582-8.

Tzemos N, Lim PO, Mackenzie IS, MacDonald TM. Exaggerated exercise blood pressure response and future cardiovascular disease. J Clin Hypertens (Greenwich). 2015;17:837-44. Doi: 10.1111/jch.12629. Epub 2015 Aug 3.

MacDonald TM, Williams B, Caulfield M, Cruickshank JK, McInnes G, Sever P, Webb DJ, Mackenzie IS, Salsbury J, Morant S, Ford I, Brown MJ. Monotherapy versus dual therapy for the initial treatment of hypertension (PATHWAY-1): a randomised double-bind controlled trial. BMJ Open. 2015;5(8):e007645. Doi:10.1136/bmjopen-2015-007645.

Brown MJ, Williams B, Morant SV, Webb DJ, Caulfield MJ, Cruickshank JK, Ford I, McInnes G, Sever P, Salsbury J, Mackenzie IS, Padmanabhan S, MacDonald TM; British Hypertension Society’s Prevention Treatment of Hypertension with Algorithm-based Therapy (PATHWAY) Studies Group. Effect of amiloride, or amiloride plus hydrochlorothiazide, versus hydrochlorothiazide on glucose tolerance and blood pressure (PATHWAY-3): a parallel-group, double-blind randomised phase 4 trial. Lancet Diabetes Endocrinol. 2016 Feb;4(2):136-47. doi: 10.1016/S2213-8587(15)00377-0. Epub 2015 Oct 18.

Williams B, MacDonald TM, Morant S, Webb DJ, Sever P, McInnes G, Ford I, Cruickshank JK, Caulfield MJ, Salsbury J, Mackenzie I, Padmanabhan S, Brown MJ; British Hypertension Society’s PATHWAY Studies Group. Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial. Lancet 2015 Nov 21:386(10008):2059-68. doi: 10.1016/S0140-6736(15)00257-3. Epub 2015 Sep 20.

Rorie DA, Rogers A, Mackenzie IS, Ford I, Webb DJ, Williams B, Brown M, Poulter N, Findlay E, Saywood W, MacDonald TM. Methods of a large prospective, randomised, open-label, blinded endpoint study comparing morning versus evening dosing in hypertensive patients: the Treatment in Morning versus Evening (TIME) study. BMJ Open. 2016 Feb 9;6(2):e010313. Doi:10.1136/bmjopen-2015-010313.

Rogers A, Flynn R, McDonnell P, Mackenzie IS, MacDonald TM. A novel drug management system in the Febuxostat versus Allopurinol Streamlined Trial (FAST): A description of a pharmacy system designed to supply medications directly to patients within a prospective multicenter randomized clinical trial. Clinical Trials 2016; DOI: 10.1177/1740774516657048.

Mackenzie IS, Ford I, Walker A, Hawkey C, Begg A, Avery A, Taggar J, Wei L, Struthers AD, MacDonald TM on behalf of the ALL-HEART study group. Multi-centre, prospective, randomised, open-label, blinded endpoint trial of the efficacy of allopurinol therapy in improving cardiovascular outcomes in patients with ischaemic heart disease: protocol of the ALL-HEART study. BMJ Open. 2016. Sep 8;6(9):e013774. DOI: http://dx.doi.org/10.1136/bmjopen-2016-013774.

MacDonald TM, Hawkey CJ, Ford I, McMurray JJ, Scheiman JM, Hallas J, Findlay E, Grobbee DE, Hobbs FD, Ralston SH, Reid DM, Walters MR, Webster J, Ruschitzka F, Ritchie LD, Perez-Gutthann S, Connolly E, Greenlaw N, Wilson A, Wei L, Mackenzie IS. Randomized trial of switching from prescribed non-selective non-steroidal anti-inflammatory drugs to prescribed celecoxib: the Standard care vs. Celecoxib Outcome Trial (SCOT). Eur Heart J. 2016 Oct 4. Pii: ehw387. [Epub ahead of print].

Mackenzie IS, Morant SV, Wei L, Thompson AM, MacDonald TM. Spironolactone use and risk of incident cancers: a retrospective, matched cohort study. Br J Clin Pharmacol. 2017; 83:653-663.

Wei L, Ratnayake L, Phillips G, McGuigan CC, Morant SV, Flynn RW, Mackenzie IS, MacDonald TM. Acid-suppression medications and bacterial gastroenteritis: a population-based cohort study. Br J Clin Pharmacol 2017; 83:1298-1308.

Rogers A, Mackenzie IS, Rorie DA, MacDonald TM. The chronotherapy of hypertension: or the benefit of taking blood pressure tablets at bedtime. British Journal of General Practice 2017 April 5. (eLetter)

Rorie DA, Flynn RWV, Grieve K, Doney A, Mackenzie I, MacDonald TM, Rogers A. Electronic case report forms and electronic data capture within clinical trials and pharmacoepidemiology. British Journal of Clinical Pharmacology 2017 March 6. Doi: 10.1111/bcp.13285. {Epub ahead of print]

MacDonald T, Williams B, Webb D, Morant S, Caulfield, MJ. Cruickshank K, Ford I, Sever P, Mackenzie I, Padmanabhan S, McCann G, Salsbury J, McInnes G, Brown MJ.  Combination therapy is superior to sequential monotherapy for the initial treatment of hypertension: a double-blind randomised controlled trial (PATHWAY 1). Journal of the American Heart Association 2017 JAHA/2017/006986-T3 (in press).

Rorie DA, Flynn RWV, Mackenzie IS, MacDonald TM, Rogers A. The Treatment in Morning versus Evening (TIME) study: analysis of recruitment, follow-up and retention rates post-recruitment. Trials 2017. 18(1):557. Doi: 10.1186/s13063-017-2318-4.

Teaching

Undergraduate, postgraduate and multidisciplinary teaching.

PGCertMedEd, University of Dundee and Train the Trainers Teaching Course completed.

Equality and Diversity Training updated 2017. Disability, Disability in the Workplace, Diversity in Learning and Teaching, Stress in the Workplace, A Manager’s Guide to Stress.

 

PhD Supervision

Research students:

PhD– David Rorie, University of Dundee 2012-2017                                                    

MD - Claudine Jennings, University of Dundee 2012-

MD - Amy Rogers, University of Dundee 2016-

MD  - JW Kerr Grieve, University of Dundee 2017-

DCAT vacation studentship 2017 – Thineskrishna Anbarasan

 

Potential students interested in working with Dr Mackenzie are encouraged to contact her to discuss opportunities for research.

Conferences

Selected invited lectures:

SHARP Tayside Meeting. Management of hypertension - as easy as ACD. Dundee, May 2013.

FAST abstracts. FAST Steering Committee Meeting, Edinburgh, May 2013.

Phaeochromocytoma: update on genetics - Diabetes and Endocrinology Meeting, Dundee, June 2013.

Presenting research using posters. Dundee Research and Academic Medicine Society (DRAMS) Meeting, Dundee, October 2013.

Spironolactone – is it time to license it for hypertension in the UK? Caledonian Society of Clinical Pharmacology Meeting, Edinburgh, November 2013.

Cardiovascular risk and rheumatological disease: the overlap. Keynote lecture. The Watson Buchanan Lecture. Scottish Society of Rheumatology Meeting, Dundee, November 2013.

Results of audit of lifestyle advice in hypertension. Cardiovascular Meeting, Dundee, January 2014.Hypertension. Medicine Meeting, Dundee, January 2014.

A diagnosis that is often missed. Medicine Meeting, Dundee, January 2014.

Methodology of the Allopurinol and Cardiovascular Outcomes in Patients with Ischaemic Heart Disease (ALL-HEART) study. Drug Safety Research Unit, Southampton, January 2014.

The ALL-HEART study. SPCRN National Meeting, Dundee, February 2014.

Management of gout. Fife Practice Learning Time Workshop, Kirkcaldy, February 2014.

Diagnosing hypertension using home and ambulatory monitoring. Tayside General Practitioners’ Meeting, Dundee, February 2014.

Hypertension. Tayside Pharmacists’ Meeting, Dundee, March 2014.

Finding the hidden secrets of medicines. Discovery Lecturer at CMDN Symposium, Crieff, February 2015.

Spironolactone use and risk of incident cancers: a retrospective matched cohort study (oral abstract presentation). Association of Physicians of Great Britain and Ireland Annual Meeting, Sheffield, March 2015.

Uric acid lowering and cardiovascular disease. Caledonian Society of Clinical Pharmacology Annual Meeting, Glasgow, May 2015.

Spironolactone use and risk of incident cancers: a retrospective matched cohort study (oral abstract presentation). British Hypertension Society Annual Meeting, Stratford-upon-Avon, September 2015.

Review of ongoing related studies. FAST Steering Committee Meeting, Edinburgh, May 2016.

Introduction to research methodology. CMT training day, Dundee, October 2016.

Hypertensive emergencies. Royal College of Physicians Edinburgh St Andrew’s Day Symposium, Edinburgh, November 2016.

ALL-HEART and all that. Edinburgh Pharmacology Symposium 2017, Edinburgh, May 2017.

Management of hyperlipidaemia, GP Forum, St Andrew’s, June 2017.