BackgroundTABLE 1 Hospital admissions for chest pain, angina <strong>and</strong> MI in Engl<strong>and</strong>, 1998–2010Chest pain Angina MIYearn LoS Days n LoS Days n LoS Days1998–9 114,828 3.0 352,706 98,198 5.3 573,135 67,116 8.2 571,2571999–2000127,379 2.9 373,162 99,562 5.2 564,750 63,397 8.2 546,3572000–1 144,148 2.9 426,269 98,772 5.4 580,097 61,760 8.6 559,3242001–2 152,721 2.8 436,342 92,332 5.4 551,913 61,716 9.0 591,9172002–3 161,931 2.6 430,799 89,435 5.5 541,421 64,415 9.5 657,1042003–4 176,887 2.0 425,389 85,066 5.0 501,108 62,032 10 666,7882004–5 205,306 2.1 431,440 81,331 5.0 452,282 61,423 9.7 687,3312005–6 224,086 1.9 414,174 77,510 4.6 401,562 59,067 9.0 638,3972006–7 236,028 1.6 379,968 73,790 4.0 331,029 56,889 8.4 587,4502007–8 233,736 1.4 345,857 69,707 3.7 292,519 54,759 8.0 538,9962008–9 246,854 1.3 332,739 67,998 3.5 272,921 53,333 7.9 510,6332009–10 253,765 1.3 331,284 63,082 3.3 234,897 50,386 7.6 461,573300,000250,000No. <strong>of</strong> hospital admissions200,000150,000100,000Chest painAnginaMI50,00001998–9 1999–2000 2000–1 2001–22002–3 2003–4 2004–5 2005–6 2006–7 2007–8 2008–9 2009–10YearFIGURE 1 Hospital admissions for chest pain, angina <strong>and</strong> MI in Engl<strong>and</strong>, 1998–2010.10–12 hours after symptom onset. 11 Patients with suspected ACS typically present to hospital within a fewhours <strong>of</strong> symptom onset, 12 so delaying blood sampling usually incurs costs <strong>of</strong> hospital observation <strong>and</strong>/oradmission. Earlier blood sampling is cheaper but may miss cases <strong>of</strong> MI, so the timing <strong>of</strong> sampling <strong>and</strong> testsused involve a trade-<strong>of</strong>f between cost <strong>and</strong> accuracy.2NIHR Journals Library
DOI: 10.3310/hta17010 Health Technology Assessment 2013 Vol. 17 No. 1Many patients with suspected ACS are known to have CAD <strong>and</strong> are receiving secondary preventativetreatment. However, a substantial proportion <strong>of</strong> 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 <strong>of</strong> CAD induced by exertional or pharmacologicalstress or anatomical imaging <strong>of</strong> the coronary arteries. Identification <strong>of</strong> CAD allows treatment withaspirin, statins <strong>and</strong> angiotensin-converting enzyme inhibitors to be commenced <strong>and</strong> consideration <strong>of</strong>coronary revascularisation for high-risk cases. The benefits <strong>of</strong> diagnosing CAD relate to the opportunityto reduce subsequent major adverse cardiac events (MACEs), particularly cardiac death <strong>and</strong> non-fatal MI.Technologies used to diagnose CAD thus also need to predict risk <strong>of</strong> adverse events to allow targeting<strong>of</strong> treatment. It could be argued that prediction <strong>of</strong> adverse events is <strong>of</strong> more practical value than thediagnosis <strong>of</strong> CAD in determining management decisions.Investigation <strong>of</strong> suspected ACS also involves identification <strong>and</strong> treatment <strong>of</strong> patients with unstable angina.These patients have CAD <strong>and</strong> worsening symptoms, but no evidence <strong>of</strong> cardiac damage. Previously theyconstituted the majority <strong>of</strong> patients with suspected ACS. However, the increasing sensitivity <strong>of</strong> biochemicaltests for myocardial damage, <strong>and</strong> the redefinition <strong>of</strong> MI to include all patients with evidence <strong>of</strong> myocardialdamage, means that patients with unstable angina <strong>and</strong> no myocardial damage are fewer in number<strong>and</strong> have a relatively low risk <strong>of</strong> adverse outcome. Furthermore, in the absence <strong>of</strong> 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 angina<strong>and</strong> 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 <strong>and</strong> Clinical Excellence (NICE). 11 These guidelines recommend measurement <strong>of</strong> troponinlevels at presentation to hospital <strong>and</strong> 10–12 hours after the onset <strong>of</strong> symptoms. This is based on evidencethat troponin levels predict subsequent risk <strong>of</strong> adverse outcome 8 <strong>and</strong> 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 <strong>and</strong> <strong>of</strong>ten incurs additional health-care costsassociated with hospital admission <strong>and</strong>/or observation. As a result, various alternative strategies have beenproposed for earlier diagnosis <strong>of</strong> MI using combinations <strong>of</strong> biomarkers, measuring biomarker gradients<strong>and</strong> 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 <strong>of</strong> recent onset recommends that patients with an elevated troponinlevel are treated for ACS according to the NICE guidance for unstable angina <strong>and</strong> NSTEMI. 14 Those witha negative troponin level should be reassessed <strong>and</strong> 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 <strong>and</strong> 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 <strong>of</strong> Cardiology guidance. 15 A survey <strong>of</strong> the management <strong>of</strong> troponin-negative patientswith acute chest pain, undertaken prior to publication <strong>of</strong> NICE guidance, showed variability in the use<strong>of</strong> risk stratification methods <strong>and</strong> subsequent use <strong>of</strong> other investigations, such as the exercise tolerancetest (ETT). 16The NICE guidelines 11 identified areas <strong>of</strong> uncertainty where further research is required. These are:1. evaluation <strong>of</strong> new, high-sensitivity troponin assay methods in low-, medium- <strong>and</strong> high-risk groups withacute chest pain, <strong>and</strong> evaluation <strong>of</strong> other putative biomarkers in comparison with the diagnostic <strong>and</strong>prognostic performance <strong>of</strong> the most clinically effective <strong>and</strong> cost-effective troponin assays© Queen’s Printer <strong>and</strong> Controller <strong>of</strong> HMSO 2013. This work was produced by Goodacre et al. under the terms <strong>of</strong> a commissioning contract issued by the Secretary <strong>of</strong> Statefor Health. This issue may be freely reproduced for the purposes <strong>of</strong> private research <strong>and</strong> study <strong>and</strong> extracts (or indeed, the full report) may be included in pr<strong>of</strong>essional journalsprovided that suitable acknowledgement is made <strong>and</strong> the reproduction is not associated with any form <strong>of</strong> advertising. Applications for commercial reproduction should beaddressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials <strong>and</strong> Studies Coordinating Centre, Alpha House, University <strong>of</strong> Southampton SciencePark, Southampton SO16 7NS, UK.3
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