Health Technology Assessment 2000; Vol. 4: No. 23
`
`Rapidreview
`
`
`Coronary artery stents in the
`treatment of ischaemic heart disease:
`a rapid and systematic review
`
`C Hyde
`
`C Meads
`
`C Cummins
`K Jolly
`A Stevens
`
`A Burls
`
`HealthTechnologyAssessment
`
`NHS R&D HTA Programme
`
`HTA
`ys
`
`Page 1
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`Standing Group on Health Technology
`
`Professor John Gabbay
`Director, Wessex Institute
`for Health Research
`& Development
`
`Professor SirJohn
`Grimley Evans
`Professor of Clinical Geratology,
`Radcliffe Infirmary,
`Oxford
`
`Dr Tony Hope
`Clinical Reader in Medicine,
`Nuffield Department of
`Clinical Medicine,
`University of Oxford
`
`Professor Richard Lilford
`Regional Director of R&D,
`NHSExecutive West Midlands
`
`DrJeremy Metters
`Deputy Chief Medical Officer,
`Department of Health
`
`Professor Maggie Pearson
`Regional Director of R&D,
`NHS Executive North West
`
`Mr Hugh Ross
`ChiefExecutive,
`The United Bristol
`Healthcare NHS Trust
`Professor Trevor Sheldon
`Joint Director, York Health
`Policy Group, University of York
`Professor Mike Smith
`Faculty Dean of Research
`for Medicine, Dentistry,
`Psychology & Health,
`University of Leeds
`
`DrJohn Tripp
`Senior Lecturerin Child
`Health, Royal Devon and Exeter
`Healtheare NHS Trust
`
`Professor Tom Walley
`Director,
`Prescribing Research Group,
`University of Liverpool
`
`DrJulie Woodin
`Chief Executive,
`Nottingham Health Authority
`
`Current members
`
`Chair:
`Professor Kent Woods
`Professor of Therapeutics,
`University of Leicester
`
`Professor Martin Buxton
`Director & Professor of
`Health Economics,
`Health Economics
`Research Group,
`Brunel University
`Professor Shah Ebrahim
`Professor of Epidemiology
`of Ageing, University ofBristol
`Professor Francis H Creed
`Professor of
`Psychological Medicine,
`Manchester Royal Infirmary
`
`Past members
`
`ProfessorSir Miles Irving”
`Professor of Surgery,
`University of Manchester,
`Hope Hospital, Salford
`DrSheila Adam
`Department of Health
`
`Professor Angela Coulter
`Director, King’s Fund,
`London
`
`Professor Anthony Culyer
`Deputy Vice-Chancellor,
`University of York
`
`ProfessorJohn Farndon
`Professor of Surgery,
`University of Bristol
`
`Professor Charles Florey
`Department of Epidemiology
`& Public Health, Ninewells
`Hospital & Medical School,
`University of Dundee
`Professor Howard
`Glennester
`Professor of Social Science
`& Administration, London
`School of Economics &
`Political Science
`
`Professor Michael Maisey
`Professor of
`Radiological Sciences,
`Guy’s, King’s & St Thomas’s
`School of Medicine & Dentistry,
`London
`
`Mrs Gloria Oates
`Chief Executive,
`Oldham NHS Trust
`
`Dr George Poste
`Chief Science & Technology
`Officer, SmithKline Beecham
`
`Professor Michael Rawlins
`Wolfson Unit of
`Clinical Pharmacology,
`University of Newcastle-
`upon-Tyne
`
`Professor Martin Roland
`Professor of General Practice,
`University of Manchester
`Professor Ian Russell
`Department of Health Sciences
`& Clinical Evaluation,
`University of York
`Dr Charles Swan
`Consultant Gastroenterologist,
`North Staffordshire
`Royal Infirmary
`
`* Previous Chair
`
`Dr Peter Doyle
`Executive Director, Zeneca Ltd,
`ACOST Committee on Medical
`Research & Health
`
`Mr John H James
`Chief Executive,
`Kensington, Chelsea &
`Westminster Health Authority
`
`Details of the membership of the HTA panels, the NCCHTA Advisory Group and the HTA
`Commissioning Board are given at the end of this report.
`
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`
`
`ti’
`=]
`
`INAHTA
`
`
`
`Howto obtain copies of this and other HTA Programmereports.
`An electronic version of this publication, in Adobe Acrobat format, is available for downloading free of
`charge for personal use from the HTA website (http://www.hta.ac.uk). A fully searchable CD-ROM is
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`
`
`Coronaryartery stents in the
`treatment of ischaemic heart disease:
`a rapid and systematic review
`
`C Meads
`
`C Cummins
`K Jolly
`A Stevens
`
`A Burls
`C Hyde’
`
`Department of Public Health and Epidemiology,
`University of Birmingham, UK
`*
`
`Corresponding author
`
`Competinginterests: none declared.
`
`Expiry date: | January 2001
`
`Published November 2000
`
`
`
`This report should be referenced as follows:
`
`Meads C, CumminsC, Jolly K, Stevens A, Burls A, Hyde C. Coronary artery stents in the
`treatment of ischaemic heart disease: a rapid and systematic review. Health Technol Assess
`2000;4(23).
`
`Health Technology Assessment is indexed in Index Medicus/MEDLINE and Excerpta Medical
`EMBASE. Copies of the Executive Summaries are available from the NCCHTA website
`(see overleaf).
`
`
`
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`NHS R&D HTA Programme
`
`he overall aim of the NHS R&D Health Technology Assessment (HTA) programme is to ensure
`that high-quality research information on the costs, effectiveness and broader impact of health
`technologies is produced in the mostefficient way for those who use, manage and work in the NHS.
`Research is undertakenin those areas where the evidence will lead to the greatest benefits to
`patients, either through improved patient outcomes or the most efficient use of NHS resources.
`
`The Standing Group on Health Technology advises on national priorities for health technology
`assessment. Six advisory panels assist the Standing Groupin identifying andprioritising projects.
`These priorities are then considered by the HTA Commissioning Board supported by the National
`Coordinating Centre for HTA (NCCHTA).
`
`The research reported in this monograph was commissioned by the HTA programme(project
`number 99/15/01) on behalf of the National Institute for Clinical Excellence (NICE), Rapid reviews
`are completed in a limited time to inform the appraisal and guideline development processes
`managed by NICE. The review brings together evidence on key aspects of the use of the technology
`concerned. However, appraisals and guidelines produced by NICEare informed by a wide range
`of sources. Any views expressed in this rapid review are therefore those of the authors and not
`necessarily those of the HTA programme, NICE or the Department of Health.
`
`Reviews in Health Technology Assessment are termed ‘systematic’ when the account ofthe search,
`appraisal and synthesis methods (to minimise biases and random errors) would, in theory, permit
`the replication of the review by others.
`
`Criteria for inclusion in the HTA monographseries
`Reports are published in the HTA monographseries if (1) they have resulted from work eitherprioritised by the
`Standing Group on Health Technology, or otherwise commissioned for the HTA programme,and (2) they are of
`
`a sufficiently high scientific quality as assessed by the referees andeditors.
`
`Series Editors: Andrew Stevens, Ken Stein and John Gabbay
`Monograph Editorial Manager: Melanie Corris
`
`The editors and publisher have tried to ensure the accuracy ofthis report but do not accept liability
`for damages or losses arising from material published in this review.
`
`ISSN 1366-5278
`
`© Crown copyright 2000
`
`Enquiries relating to copyright should be addressed to the NCCHTA(see address given below).
`
`Published by Core Research, Alton, on behalf of the NCCHTA.
`Printed on acid-free paper in the UK by The Basingstoke Press, Basingstoke.
`
`Copies of this report can be obtained from:
`
`The National Coordinating Centre for Health Technology Assessment,
`Mailpoint 728, Boldrewood,
`University of Southampton,
`Southampton, SO16 7PX, UK.
`Fax: +44 (0) 23 8059 5639=Email: hta@soton.ac.uk
`http://www.ncchta.org
`
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`Health Technology Assessment 2000; Vol. 4: No. 23
`
`Contents
`
`Glossary and list of abbreviations..............
`
`i
`
`Appendix | Manufacturers’ submissions ...
`
`59
`
`Executive SUMMAPY.........ccs il
`
`Appendix 2 Effectiveness search strategy...
`
`61
`
`Appendix 3 Cost searchstrategy...65
`1
`| Review aims and background...................
`1
`Aims..
`
`Appendix 4 Economic evaluation
`I
`Introduction.. we
`vets
`S€arch SUral€QY oesBF
`l
`Description ofhealthproblemwees
`,
`;
`Currentservice provision wo6 .
`Implications for the NHS «0.0.0.0:9 Appendix 5 Tables of results of review
`Of CHEECTIVETNESS Voie ccceecseeesteetieesseeeeeee
`2 Methods oo.ccsLI
`
`Review questions..
`..
`Il
`Search Strate@y voceeee Ld
`Inclusion and exclusion¢criteria
`(clinical effectiveness) .......ccccceeeseeseeeeee
`Inclusion and exclusion criteria
`weer
`(economic evaluation)..........
`Data abstraction (clinicaleffectiveness)senses
`Data abstraction (economicevaluation) ......
`Quality assessment (clinical effectiveness)...
`Quality assessment (economic evaluation)...
`Data synthesis (clinical effectiveness) ...........
`
`Data synthesis (economic evaluation) ...........
`
`12
`
`13
`13
`13
`13
`13
`14
`14
`
`3 Results oo. cceececeecseeseesereseeee
`
`Introduction
`
`Effectiveness results..........
`a
`weve.
`Results of economic evaluationsrTEVIEW oo...
`
`15
`
`15
`15
`36
`
`4 Discussion and conclusions ....................... 43
`Results summary...........
`wee 43
`Potential methodological‘strengthsand
`weaknesses of thetechnology assessment .... 46
`Conclusions............
`cettetesentseessteecesseee
`47
`Implications ofaassessmentfindinPS receAT
`
`Acknowledgements ..........ccee AD
`
`References ...0..0.ee OL
`
`69
`
`Appendix 6 PTCA costs w..cciccceeee 119
`
`Appendix 7 Stents costs .......... cece 123
`
`Appendix 8 CABGcosts wee 125
`Appendix9}Smdytytypes of economic
`amalyses -...cee.
`oe197
`Appendix 10 Summary table of economic
`analyses (MOdels) .....ccceeeseeseeeeeeeeecee 129
`
`Appendix 11 Summary of economic
`analyses (individual studies) .........000..00. 133
`
`Appendix 12 Source ofcost data for
`ECONOMIC ANALYSES «2.0.0... eee eee 137
`
`Appendix 13 Outcome measures reported
`by individual economic analyses................. 139
`Appendix 14 Quality assessment of
`included economic studies ............c0000L41
`Health Technology Assessment reports
`published to date ..............:ccccceeseesreeeeee 145
`
`Health Technology Assessment
`panel membership .............00.0..0000:0149
`
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`Health Technology Assessment 2000; Vol. 4: No. 23
`
`Glossary and list of abbreviations
`
`Technical terms and abbreviations are used throughout this report. The meaningis usually clear from
`the context but a glossary is provided for the non-specialist reader. In some cases usage differs in the
`literature but the term has a constant meaning throughout this review.
`
`continued
`
`Glossary
`Abciximab A glycoprotein IIb/IIIa
`antagonist, used to inhibit blood clotting.
`
`Acute coronary syndrome Severe
`symptomatic coronary artery disease
`including unstable angina and non-Q wave
`myocardial infarction.
`
`ECG Electrocardiogram— mapselectrical
`activity in the heart muscle. ECG findings
`might include Q waves or ST elevation
`
`Exercise stress test Diagnostic test used to
`find exercise-induced ECG changesindicating
`myocardial ischaemia
`
`Angina Pain in the heart muscle due to lack
`of blood-borne oxygen, it is usually induced
`by exercise and relieved byrest.
`
`Angiography Radiographic technique using
`contrast medium to showoutline of coronary
`artery lumens.
`
`Elective Non-emergency treatment.
`
`Graft (saphenous vein) Insertion ofgraft
`vessel into coronary artery during coronary
`artery bypass grafting (CABG).
`
`Heterogeneity Variability or differences
`between studies.
`
`Angioplasty Short for percutaneous
`transluminal coronary angioplasty (PTCA).
`
`Atherosclerosis A disease of the arteries
`
`in whichfatty plaques develop on their
`inner walls leading to reduced blood flow
`or obstruction.
`
`Bailout stent Stent inserted as an emergency
`during PTCA because ofdissection ofthe
`vessel wall.
`
`Braunwald Classification Classification of
`
`unstable angina.
`
`Cardiac catheterisation Passing a catheter
`from femoral artery into coronaryarteries
`for angiography or percutaneous coronary
`intervention (PCI).
`
`Clopidogrel Drug that inhibits platelet
`function, now usedinstead of warfarin
`during stent placement.
`
`Creatinine kinase A cardiac enzyme, the
`blood levels of which are raised during
`myocardial infarction.
`
`Hypertension High bloodpressure.
`
`Invasive treatment Usedin this report to
`refer to PCI or CABG.
`
`Ischaemia Lack ofblood flow or oxygen.
`
`Lumen Thespace within a bloodvessel.
`
`MEDLINEA database of medical journal
`articles.
`
`Meta-analysis Methodof combining
`results from different studies to produce
`a summary statistic.
`
`Minimally invasive CABG CABG technique
`using a small thoracotomy only and not
`always requiring stopping of the heart during
`the operation.
`
`Myocardium Heart muscle.
`
`Myocardial infarction Death of a segment
`of heart muscle because of severe ischaemia.
`
`Ostial lesion Lesion of the ostium of
`
`coronary artery (whichis difficult to stent).
`
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`Glossary andlist of abbreviations
`
`
`
`during stent placement.
`
`Glossary contd
`Platelets Blood constituents involved in
`blood clot formation.
`
`Provisional stenting Stent placement
`depending on suboptimal result of PTCA.
`
`Q wave Anabnormal wave on ECG
`indicating past myocardial infarction.
`
`Reocclusion Repeat complete blockage of
`coronary artery.
`
`Restenosis Re-narrowing ofcoronaryartery.
`
`Revascularisation Maintaining or improving
`coronary artery blood supply.
`
`Silent ischaemia Ischaemia of heart muscle
`found with exercise stress test where patient
`has no angina symptoms.
`
`Stent Small prosthesis inserted into coronary
`artery to keep the lumen open.
`
`Subacute ischaemic heart disease All
`manifestations of ischaemic heart disease
`
`except acute myocardial infarction.
`
`Thrombus Bloodclot.
`
`Ticlopidine Drug that inhibits platelet
`function, now usedinstead of warfarin
`
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`Health Technology Assessment 2000; Vol. 4: No. 23
`
`
`
`List of abbreviations
`
`AMI
`
`BCIS
`
`CABG
`
`CAD
`CEA
`CI
`CK-MB
`
`co
`cost/EFS
`cu
`CVA
`
`DARE
`
`DEC
`
`DFI
`
`eCABG
`EFS
`
`acute myocardial infarction
`(see myocardial infarction)
`British Cardiovascular
`
`Intervention Society
`
`coronary artery bypass
`graft(ing)
`
`coronary artery disease
`cost-effectiveness analysis
`confidenceinterval (95%)
`creatine kinase
`
`chronic coronary occlusion”
`cost per event-free survivor
`cost-utility study"
`cerebrovascular accident
`
`(stroke)
`Database of Abstracts of
`Reviews of Effectiveness
`
`Development and
`Evaluation Committee
`
`Dutch Guilder
`
`emergency CABG
`event-free survival or survivor
`
`EUROQOL
`
`IHD
`
`INR
`
`standardised assessment
`method for quality of
`life (used in cost—
`utility studies)
`ischaemic heart disease
`
`International
`Normalised Ratio’
`
`LAD artery
`
`left anterior descending
`coronary artery
`
`LMW heparins
`
`LoS
`LVEF
`
`MACCE
`
`MACE
`
`low molecular weight
`heparins (used for blood
`anticoagulation)*
`length of stay
`left ventricular ejection
`fraction (measure of
`heart performance)
`major adverse coronary and
`cerebrovascular events
`
`major adverse
`coronary events
`
`minimal lumen diameter
`
`*
`
`of coronary artery
`.
`.
`multi-vessel coronary disease
`.
`=
`not applicable
`*
`not clear
`
`+
`
`not recorded
`.
`.
`.
`.
`not statistically significant
`NHS Economic
`Evaluations Database
`
`*
`
`National Institute for
`Clinical Excellence
`
`National Service Framework
`
`odds ratio
`
`percutaneous coronary
`intervention (includes PTCA,
`atherectomy, excimerlaser,
`rotablator, stents)
`
`.
`o
`.
`*
`previous myocardial
`infarction
`
`percutaneous transluminal
`coronary angioplasty
`
`person years at risk
`
`quality adjusted life-year
`quality of life”
`randomised controlled trial
`
`stable angina’
`standard deviation”
`
`Short Form 36
`
`standardised mortality ratio
`
`single vessel coronary
`disease
`
`Thrombolysis In Myocardial
`Infarction flow grade
`[0 (poor) - 4 (good) ]"
`target lesion
`revascularisation
`
`target vessel revascularisation
`unstable angina’
`
`MVD
`
`N/A
`
`N/C
`NR
`
`NS
`
`NHSEED
`
`NICE
`
`NSF
`
`OR
`
`PCI
`
`PMI
`
`PTCA
`
`PYAR
`
`QALY
`
`QOL
`RCT
`
`SA
`
`sD
`
`SF-36
`
`SMR
`
`SVD
`
`TIMI flow grade
`
`TLR
`
`TVR
`UA
`
`years oflife lost
`YLL
`myocardial infarction
`MI
`
`" Used only in tables ae
`(heart attack)
`
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`Health Technology Assessment 2000; Vol. 4: No. 23
`
`Executive
`
`summary
`
`Background
`
`Methods
`
`Coronary artery stents are prosthetic linings
`inserted into coronaryarteries via a catheter
`to widen the artery and increase blood flow to
`ischaemic heart muscle. They are used in the
`treatment of ischaemic heart disease (IHD).
`
`IHD is a major cause of morbidity and mortality
`(123,000 deaths per annum) in the UK and a
`major cost to the NHS. Clinical effects of THD
`include subacute manifestations (stable and
`unstable angina) and acute manifestations
`(particularly myocardial infarction [MI]).
`Treatmentincludes attention to risk factors,
`drug therapy, percutaneousinvasive interventions
`(PCIs) (including percutaneous transluminal
`coronary angioplasty [PTCA] and stents) and
`coronary artery bypass graft surgery (CABG).
`
`In the last decade there has been a steady and
`significant increase in the rate of PCIs for THD.
`In the UK, rates per million population increased
`from 174 in 1991 to 437 in 1998. Stents are now
`used in about 70% of PCIs. Data fromthe rest of
`Europe suggest there is potential for PCI and stent
`rates to increase considerably. In the UK thereis
`evidence of under-provision and inequity of
`access to revascularisation procedures.
`
`Objectives
`
`The following questions were addressed,
`
`1. What are the effects and effectiveness of elective
`stent insertion versus PTCA in subacute THD,
`particularly stable angina and unstable angina?
`2. What are the effects and effectiveness ofelective
`stent insertion versus CABG in subacute THD,
`particularly stable angina and unstable angina?
`3. What are the effects and effectiveness ofelective
`
`stent insertion versus PTCA in acute MI (AMI)?
`4, Whatare best estimates of UK cost for elective
`stent insertion, PTCA and CABGin the
`circumstances of review questions | to 3?
`5. Whatare best estimates of cost-effectiveness and
`
`cost-utility for elective stent insertion relative to
`PTCA or CABGinthe circumstances of review
`
`questions | to 3?
`
`A systematic review addressing the objectives
`was undertaken.
`
`Data sources
`
`A search was made for RCTs comparing stents
`(inserted during a PTCA procedure) with PTCA
`alone or with CABGin any manifestation of IHD.
`Thesearch strategy coveredthe period from 1990 to
`November 1999 andincludedsearches ofelectronic
`databases (MEDLINE, EMBASE, BIDS ISI, The
`CochraneLibrary), Internet sites, and handsearches
`of cardiology conference abstracts and 1999 issues
`ofcardiologyjournals. Lead researchers andlocal
`clinical experts were contacted. Manufacturers’ sub-
`missions to the National Institute for Clinical
`Excellence were searched.
`
`The search strategy was expandedto look for
`relevant economic analyses and information to
`inform the economic model (including searching
`MEDLINE, the NHS Economic Evaluation Data-
`base and the Database of Abstracts of Reviews of
`
`Effectiveness). Searches focused on research that
`reported costs and quality oflife data associated
`with IHD andinterventional cardiology.
`
`Study selection
`For the review ofclinical effectiveness, inclusion
`criteria were: (i) RCT design; (ii) study population
`comprising adults with IHDin native or graft
`vessels (including patients with subacute IHD or
`AMI); (iii) procedure involving elective insertion
`ofcoronary artery stents; (iv) elective PTCA (in-
`cluding PTCA withprovisional stenting) or CABG
`as comparator; (v) outcomes defined as one or
`more of: combined event rate (or event-free sur-
`vival), death, MI, angina, target vessel revascular-
`isation, CABG, repeat PTCA, angiographic
`outcomes; (vi) trials that had closed and reported
`results for all or almostall recruited patients.
`
`For the economic evaluation, studies of adults with
`IHDwere includedif they were ofthe following
`types: studies reporting UK costs; comparative
`economic evaluation combining both costs and
`outcomes; economic evaluations reporting costs
`and outcomes separately for the years 1998 and
`1999 (to ensure current practice was included).
`
`v
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`Executive summary
`
`Data extraction
`For the review ofclinical effectiveness, data were
`extracted into data extraction forms and RCT
`quality was assessed using standard methods.
`Decisions relating to data extraction and quality
`were made by two independent reviewers. Dis-
`agreements were resolved by discussion and with
`the aid ofa third party if there was any residual
`discrepancy. The quality assessment ofcost-
`effectiveness analyses was based on a pre-
`determined check-list.
`
`Data synthesis
`For the review of clinical effectiveness, abstracted
`data were collated in summary tables. Whenever
`possible, analysis was on an intention-to-treatbasis.
`Meta-analyses were carried out when adequate
`data wereavailable.
`
`Costs and economic analyses
`The information identified contributes only to
`conclusions concerning elective stent insertion
`compared with PTCA in subacute IHD. There
`was wide variation in the estimates of cost, cost-
`effectiveness andcost-utility. Cost estimation,
`particularly for wider costs, was generally poor.
`It was probably conducted best in the context of
`the cost-effectiveness studies. These generally
`showed that cost/event-free survivor for elective
`stenting was equivalent to or less than that of
`PTCA. They support the view that higherinitial
`costs of stents are outweighed by savings from
`reduced requirement for repeat PTCA. The
`majority of cost-utility studies reported cost/
`QALYestimations in the range of £20,000-—
`£30,000. Reasons why these estimates should
`be treated with caution were identified.
`
`For the economic evaluation, cost data and
`health economic assessments were documented
`andevaluated,
`
`The efficiency of the use of stents compared with
`CABGin subacute IHD or stents comparedwith
`PTCAin AMI is unknown.
`
`Results
`
`Conclusions
`
`Effects and effectiveness
`Thirty-five RCTs whichfulfilled the study criteria
`were found: 25 compared stent with PTCA for
`subacute IHD; three compared stents with CABG
`for subacute IHD; seven compared stents with
`PTCA following AMI. In general, the trials were
`opento bias, which introduced uncertainty.
`Despite this, convincing evidence ofimpact
`was identified in the following.
`
`1. Elective stent insertion versus PTCA in subacute
`IHDfor:
`
`* event rates (generally death, MI, repeat PTCA
`and CABG) — oddsratio (OR), 0.68 (95%
`confidence interval [CI], 0.59 to 0.78)
`repeat PTCA — OR, 0.57 (95% CI, 0.48
`to 0.69)
`2. Elective stent insertion versus PTCA in
`AMI for:
`
`*
`
`* event rates (generally death, MI, repeat
`PTCA and CABG) — OR, 0.39 (95% CI,
`0.28 to 0.54)
`repeat PTCA — OR,0.44 (95% CI, 0.26
`to 0.74).
`
`*
`
`There was no clear evidence of impact on deaths,
`MI or CABGin comparison (1) or (2) above.
`Althoughtrials were identified, there was insuffi-
`cient evidence to draw any conclusions on the
`effectiveness ofelective stent insertion versus
`CABGin subacute IHD.
`
`In subacute IHD (especially stable angina and
`unstable angina), there is evidence for the effec-
`tiveness of elective stents in reducing the need
`for repeat PTCA. This appears to represent an
`efficient use of resources. However, this assertion
`could be made with more confidence if the
`
`resource neutrality of stents could be confirmed
`using more rigorously derived cost data. There
`is currently insufficient evidence to assess the
`effectiveness of the extension of stent use to
`patients with baseline risks or indications different
`from those ofthe patients in thetrials reviewed
`(for review question 1).
`
`Recommendations for further
`evaluation and research
`1. For many important stenting applications,
`research is ongoing and a reassessment of
`research evidence and health economic evalu-
`
`ations in 1-2 years’ time would bevaluable.
`2. Further research on the use of stents is needed
`to: acquire better cost data, using explicit
`micro-costing; investigate the impact of
`stents on severity of angina and quality
`of life; evaluate the effectiveness of
`newer technologies.
`3. It is very importantto establish clearly the
`effectiveness and efficiency of stents compared
`with CABG, and even thoughthereis
`considerable ongoing research in this area,
`further targeted research may be valuable.
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`Health Technology Assessment 2000; Vol. 4: No. 23
`
`Chapter |
`
`Review aims and background
`
`Aims
`
`* To assess the effectiveness of coronary artery
`stents comparedwith other established
`revascularisation procedures (percutaneous
`transluminal coronary angioplasty [PTCA]
`alone and coronary artery bypass grafting
`[CABG]) in the main manifestations of
`ischaemic heart disease (IHD).
`e To assess the costs, cost-effectiveness and
`cost-utility of the above.
`
`Introduction
`
`A coronary arterystent is a metal tube, coil or
`mesh that is inserted into a coronaryartery, via a
`catheterinserted in anartery in the groin or arm,
`in order to widen the coronary artery and improve
`the blood flowto ischaemic heart muscle.
`
`Interventional cardiologists are increasingly using
`coronary artery stents to treat IHD.' The procedure
`is carried out in a cardiac catheterisation lab-
`
`oratory. The stents can be inserted as anelective
`procedure (elective stenting), or after a PTCA
`with sub-optimal results (‘provisional stenting’)
`or where there is an acute closure of the artery
`after PTCA (emergency or ‘bailout’ stenting).
`
`Description of health problem
`
`Disease
`IHDis caused by aninsufficient supply of oxygen
`to the heart muscle. It can be ‘silent’ (when the
`patient has no symptoms) or can cause angina,
`unstable angina, myocardial infarction (MI)
`or death.
`
`In this report we distinguish between acute
`myocardial infarction (AMI) and the subacute
`manifestations of IHD, particularly angina and
`unstable angina.
`
`Pathology
`IHD is generally caused by constriction or blockage
`of the coronaryarteries supplying the heart. This is
`also known as coronary artery disease (CAD). The
`vast majority of IHD is due to atheromaandits
`
`complications. Atheroma occurs when thereis
`damageto the linings ofarteries leading to the
`formation ofraised patches offibrous and fatty
`material, knownas atheromatous plaques.
`
`Epidemiology
`IHD is the major cause of death of men and
`womenin the UK.” In 1997 there were 122,780
`deaths due to IHD in the UK (22% ofall deaths
`and 25% of deaths in men).*
`
`Although deaths from IHD have fallen over by
`over two-thirds in the last 30 years, UK rates remain
`higher than in many countries (e.g. the death rate
`in the UK is over three times that ofFrance, the
`EU country with the lowest death rate).* When
`measuredin terms of years oflife lost (YLL), IHD
`accounts for 15.6% ofall years oflife lost (1,365,995
`YLL peryear). Thefigure is 19.3% for men.”
`
`It is estimated that, in Europe, [HDis the leading
`single cause of disability accounting for 9.79% of
`total disability adjusted life-years.® Given the high
`incidence of IHD in England and Wales, the
`figure will be even higher here.
`
`Theresults of the 1998 Health Survey for England®
`indicate an overall prevalence of IHD of 7.1%in
`men and 4.6% in women. Prevalence increases
`markedly with age, reaching 23.4% in men and
`18.4% in women aged over 75 years. The point
`prevalence ofanginais estimated to be 3.2%
`for men and 2.5% for women; 5.3% of men and
`3.9% of womenreported ever having had angina.
`Overall 4.2% of men and 1.8% of women reported
`having hada heart attack (0.6% of men and
`0.3% of womenreported havingit within the
`last 12 months).®
`
`The Fourth General Practice Morbidity Survey
`(1991-1992)° gives the prevalence and incidence
`rates per 10,000 person years at risk (PYAR) for
`AMI and angina pectoris® (Table 1). Comparison
`of the Fourth Survey with the Third General
`Practice Morbidity Survey (1981) suggests that
`therates for angina are rising.”
`
`Aetiology
`Cigarette smoking and other tobacco use are
`associated with an increase in atheroma and
`
`I
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`Review aims and background
`
`TABLE | Prevalence and incidence rates ofAMI and angina per
`10,000 person years atrisk (PYAR)’
`
`revascularisation (PTCA and CABG), which are
`increasingly being replaced by stenting.
`
`Prevalence
`
`Incidence
`
`Men Women
`
`Men Women
`
`AMI
`
`Angina
`
`38
`
`130
`
`20
`
`98
`
`29
`
`55
`
`16
`
`49
`
`are a majorrisk factor for IHD. Diabetes mellitus,
`hypertension, raised cholesterol, genetic pre-
`disposition, diet, lack of exercise and obesity
`are also risk factors.
`
`Manyofthese risk factors can be modified
`and IHD hasbeenidentified as a major con-
`tributor to avoidable mortality. Reduction in
`circulatory disease mortality is a major UK
`governmenttarget in the strategy to improve
`the nation’s health.”
`
`Treatments of established IHD
`Introduction
`
`Althoughpreventing IHD is important, this
`paperis concerned with the treatments that aim
`to reduce both the morbidity and the mortality
`in patients with established IHD. Treatment of
`THD has many modalities:
`
`¢ modification of risk factors
`
`* medical management
`* percutaneousinvasive treatments (carried out
`by interventional cardiologists)
`* surgical interventions.
`
`Medical treatments have many mechanisms of
`action and rationales. They may aim to:
`
`reduce risk factors causing IHD
`*
`reduce the physical demand onthe heart
`*
`improve the blood flowwithin the heart
`*
`* alter the clotting characteristics of blood.
`
`There are now many well established treatments for
`both THD and manyofits risk factors. Many clearly
`contribute to both alleviation of symptoms and
`prevention of adverse events, such as AMI and
`death. The aims oftreatment are to prolonglife,
`prevent MI, prevent damage to the heart and heart
`failure, relieve painful and disabling angina and
`other symptoms, and improve quality of life.
`
`This paper does not review the evidencefor all
`of these treatments or discuss their relative merits,
`but concentrates on coronary arterystenting
`
`It is useful to have a brief overview ofrevascular-
`
`isation techniques over the last 30 years in order
`to understand why stents were developed. Initially,
`revascularisation began in order to provide altern-
`ative therapy when medical treatments failed to
`control symptoms. The basic aim ofall revascular-
`isation procedures is to provide a better lumen in
`the vessel supplying heart muscle to improve
`bloodflow.
`
`CABG
`
`CABGis a surgical technique that involves opening
`the chest wall and bypassing a blocked or narrowed
`section of a coronary artery, usually by