Systematic review, meta-analysis and economic modelling of ...

DOI: 10.3310/hta17010 Health Technology Assessment 2013 Vol. 17 No. 1Many patients with suspected ACS are known to have CAD and are receiving secondary preventativetreatment. However, a substantial proportion of patients have not previously been investigated forCAD. Once MI has been ruled out these patients may be investigated for underlying CAD by eitherprovocative cardiac testing to identify symptoms of CAD induced by exertional or pharmacologicalstress or anatomical imaging of the coronary arteries. Identification of CAD allows treatment withaspirin, statins and angiotensin-converting enzyme inhibitors to be commenced and consideration ofcoronary revascularisation for high-risk cases. The benefits of diagnosing CAD relate to the opportunityto reduce subsequent major adverse cardiac events (MACEs), particularly cardiac death and non-fatal MI.Technologies used to diagnose CAD thus also need to predict risk of adverse events to allow targetingof treatment. It could be argued that prediction of adverse events is of more practical value than thediagnosis of CAD in determining management decisions.Investigation of suspected ACS also involves identification and treatment of patients with unstable angina.These patients have CAD and worsening symptoms, but no evidence of cardiac damage. Previously theyconstituted the majority of patients with suspected ACS. However, the increasing sensitivity of biochemicaltests for myocardial damage, and the redefinition of MI to include all patients with evidence of myocardialdamage, means that patients with unstable angina and no myocardial damage are fewer in numberand have a relatively low risk of adverse outcome. Furthermore, in the absence of ECG changes thereare substantial difficulties defining which patients have unstable angina, as the diagnosis is based onunreliable clinical features. These factors make it difficult to define the population with unstable anginaand estimate any benefits from treatment, beyond secondary prevention for underlying CAD.Current service provisionAcute chest pain due to possible ACS is managed in the NHS according to guidance issued by the NationalInstitute for Health and Clinical Excellence (NICE). 11 These guidelines recommend measurement of troponinlevels at presentation to hospital and 10–12 hours after the onset of symptoms. This is based on evidencethat troponin levels predict subsequent risk of adverse outcome 8 and response to treatment, 9 but do notachieve optimal sensitivity until 10–12 hours after symptom onset. 10 However, delaying blood testing until10–12 hours after symptom onset is inconvenient for patients and often incurs additional health-care costsassociated with hospital admission and/or observation. As a result, various alternative strategies have beenproposed for earlier diagnosis of MI using combinations of biomarkers, measuring biomarker gradientsand using newer, more sensitive troponin assays. A survey undertaken prior to NICE guidance beingissued 13 suggested substantial variation in the biomarker strategies used. It is not known whether or notNICE guidance has reduced this variation.The NICE guidance for chest pain of recent onset recommends that patients with an elevated troponinlevel are treated for ACS according to the NICE guidance for unstable angina and NSTEMI. 14 Those witha negative troponin level should be reassessed and if myocardial ischaemia is suspected then patientsare managed as an outpatient according to the guidance for stable chest pain. 11 This involves coronaryartery calcium (CAC) scoring and computed tomographic coronary angiography (CTCA) for selected cases.Exercise testing is not recommended in NICE acute chest pain guidance, although it is recommended inEuropean Society of Cardiology guidance. 15 A survey of the management of troponin-negative patientswith acute chest pain, undertaken prior to publication of NICE guidance, showed variability in the useof risk stratification methods and subsequent use of other investigations, such as the exercise tolerancetest (ETT). 16The NICE guidelines 11 identified areas of uncertainty where further research is required. These are:1. evaluation of new, high-sensitivity troponin assay methods in low-, medium- and high-risk groups withacute chest pain, and evaluation of other putative biomarkers in comparison with the diagnostic andprognostic performance of the most clinically effective and cost-effective troponin assays© 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.3