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Appendix 9respectively. Exercise ECG would therefore be expected to miss a significant proportion of patients withCAD while subjecting others with normal coronary arteries to an unnecessary invasive coronary angiogram.Multislice CT coronary angiography may provide a more accurate and cost-effective alternative to exerciseECG in troponin negative patients with suspected ACS. As with exercise ECG, most studies have evaluatedCT coronary angiography in patients with stable symptoms rather than suspected ACS. A recent systematicreview of 21 diagnostic accuracy studies of CT coronary angiography reported a pooled sensitivity of 99%and specificity of 89% for detection of CAD [16]. On the basis of this and similar analyses it has beenrecommended that CT calcium scoring with CT coronary angiography for selected patients replace exerciseECG [1].It is not yet clear whether CT coronary angiography could have a similar role in suspected ACS. Four studies(N = 103, 120, 55 and 48) have evaluated it’s use to detect CAD in patients with suspected ACS, yieldingsensitivities of 92 to 100% and specificities of 46% to 92%, depending upon the diagnostic criteria used[17–20]. These studies suggest that CT coronary angiography may be used to rule out significant CADin patients with troponin negative suspected ACS, but that limited specificity may increase unnecessaryinvestigations and health-care costs.Two economic analyses from the United States have used modelling to estimate the cost-effectiveness ofCT coronary angiography in patients with suspected ACS [21,22]. Both models suggested that CT coronaryangiography is cost-effective compared with exercise ECG or stress echocardiography. However, neitheranalysis involved comparison to a no further testing alternative. Exercise ECG is known to have limiteddiagnostic accuracy for CAD so it may represent an inefficient comparator. Furthermore, it is not clearwhether findings from the high-cost North American health-care system will be reproduced in the NHS.Cost-effectiveness analysis is required to compare CT coronary angiography and exercise ECG to eachother and an alternative of no routine testing for patients with troponin negative suspected ACS. This willallow us to determine what is the optimal strategy for the NHS on the basis of currently available data.It will also allow us to identify whether primary research in the form of a trial is required and if so, whatalternatives should be compared and outcomes measured.Research methodsDesignWe plan to undertake a cost-effectiveness analysis based on secondary research (systematic review,meta-analysis and decision-analysis modelling) to determine the most appropriate biomarker strategy forinvestigating patients with suspected ACS and determine whether CT coronary angiography or exerciseECG should be used to investigate troponin negative patients with suspected ACS.Systematic reviews and meta-analysisSystematic reviews and meta-analysis will be used to estimate the diagnostic and/or prognostic value ofbiomarkers, CT coronary angiography and exercise ECG in patients with suspected ACS. Systematic reviewswill also be used to estimate the effectiveness of treatments for MI and CAD and estimate parametersrequired for the model.There are a large number of published studies of biomarkers in suspected ACS but many are either ofpoor quality, due to lack of rigorous follow-up or an appropriate reference standard, or limited relevancebecause they have recruited a selected cohort of patients (for example, those with few or no co-morbiditiesor patients selected for coronary care admission). We plan to select studies for inclusion only if theyhave an appropriate reference standard and/or adequate follow-up, and only if they recruit unselectedpatients presenting to hospital with suspected ACS. Furthermore, we do not intend to repeat the existingsystematic reviews of exercise ECG and CT coronary angiography in patients with stable symptoms andsuspected CAD but will instead identify studies recruiting patients with suspected ACS.180NIHR Journals Library
DOI: 10.3310/hta17010 Health Technology Assessment 2013 Vol. 17 No. 1We will search the literature for prospective cohort studies of biomarkers, CT coronary angiography andexercise ECG in unselected patients presenting to hospital with suspected ACS in which at least 80% of thecohort receives either:1. Diagnostic testing for either MI using the universal definition or CAD using coronary angiography2. Follow up to identify major adverse cardiac events up to at least 30 days after presentationWe will specifically search for studies of the following biomarkers: troponin, creatinine kinase MB,myoglobin, C-reactive protein, myeloperoxidase, B-type natriuretic peptide, heart-type fatty acid-bindingprotein, copeptin, ST-2 and galectin-15.We will also use literature reviews to estimate the following parameters for the decision analysis model:1. The effect of current treatments for MI upon mortality and adverse outcomes2. The effect of secondary prevention upon long term CAD mortality and morbidity.3. Quality-adjusted life expectancy after MI and with CAD.4. The prevalence of MI and CAD and rate of adverse outcomes in a typical NHS population withsuspected ACS.5. Other characteristics of the typical population with suspected ACS: age, gender, prevalence of CADand risk factors for CAD, clinical features, risk score profiles, and prevalence of abnormal test results(ECG, troponin, creatinine).6. Long-term costs of care after event-free treatment for MI, after non-fatal adverse events and for CAD.A hierarchical approach will be used so that the most valid and relevant estimates are given priority (i.e.randomised controlled trials for effectiveness data and prospective cohort studies for prognostic data),while data with low validity or relevance are excluded. Recent published systematic reviews will be used ifthey are of acceptable quality.Search strategyRelevant studies will be identified through electronic searches of key databases including MEDLINE,EMBASE, Science Citation Index and Biological Abstracts. Published empirical work will be used to identifyoptimal strategies for prognosis and diagnosis on MEDLINE and EMBASE [23–26]. A single search strategywill be used to identify all citations that include (a) a term or abbreviation for one of the technologies(including the named biomarkers above), (b) a term or abbreviation for ACS, MI or CAD, and (c) filter forcohort or diagnostic studies.References will also be located through review of reference lists for relevant articles and through use ofcitation search facilities through the Web of Knowledge’s Science Citation Index and Social Science CitationIndex. Where existing systematic reviews already exist, these will be used both to identify relevant studiesand to inform subsequent analysis. In addition systematic searches of the Internet using the Copernicmeta-search engine will be used to identify unpublished materials and work in progress. Key authors andprofessional and academic research groups will also be contacted and asked for unpublished material.Review strategyThe stages of the review will include:1. Accumulation of references, entry and tagging on a Reference Manager database, enabling studies tobe retrieved in each of the above categories by either keyword or textword searches.2. Two reviewers will independently undertake preliminary review to identify any potentially relevantarticle based on titles, abstracts and subject indexing. All studies identified for inclusion, together withthose where a decision on inclusion is not possible from these brief details, will be obtained for moredetailed appraisal.© Queen’s Printer and Controller of HMSO 2013. This work was produced by Goodacre et al. under the terms of a commissioning contract issued by the Secretary of Statefor Health. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journalsprovided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should beaddressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton SciencePark, Southampton SO16 7NS, UK.181
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DOI: 10.3310/hta17010 Health Techno
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ContentsAppendix 5 Expected discoun
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BackgroundTABLE 1 Hospital admissio
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Background2. investigation of the c
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BackgroundComputed tomographic coro
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Research questionsiii. the diagnost
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Discussionspecificity were 62% (95%
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Discussionneed for revascularisatio
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Discussionchanges in sensitivity an
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Discussionuncertainty about these p
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Discussiontroponin assays have bett
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ConclusionsSuggested research prior
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Page 156 and 157: Appendix 1135. interleukin 33.mp. (
Page 158 and 159: Appendix 147. 37 and 45 (529)48. li
Page 164 and 165: Appendix 313. Fernandez Portales JG
Page 166 and 167: Appendix 346. Luscher MS, Ravkilde
Page 168 and 169: Appendix 316. Rao SV, Ohman EM, Gra
Page 198 and 199: Appendix 9Clinical diagnosis of NST
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Page 204 and 205: Appendix 9The methodology used in t
Page 206 and 207: Appendix 9ES (Information Resources
Page 208: Appendix 923. Westwood ME, Whiting
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