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

Appendix 9Clinical diagnosis of NSTEMI, according to the universal definition of MI [5], is based upon an elevation ofcardiac biomarkers (preferably troponin) above the 99th percentile of the upper reference limit. Patientswith an elevated troponin have an increased risk of adverse outcome and can benefit from hospitaladmission and treatment. However, troponin does not achieve optimal sensitivity for MI until several hoursafter the symptoms of MI [6] so guidelines typically recommend delaying sampling until 10–12 h aftersymptom onset. Most patients with suspected ACS present to hospital within a few hours of symptomonset, so delaying blood sampling usually incurs costs of hospital observation and/or admission. Earlierblood sampling is cheaper but may miss cases of MI, so the timing of sampling and tests used involve atrade-off between cost and accuracy.Diagnosis of underlying CADMany 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 pharmacological stressor anatomical imaging of the coronary arteries. Identification of CAD allows treatment with aspirin,statins and angiotensin converting enzyme inhibitors to be commenced and consideration of coronaryrevascularisation for high-risk cases.Unstable anginaInvestigation 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 there aresubstantial difficulties defining which patients have unstable angina, since the diagnosis is based uponunreliable 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.Uncertainties in the investigation of suspected ACSThere have been many published guidelines for the investigation of suspected ACS. Most recently theNational Institute for Health and Clinical Excellence (NICE) has issued draft guidance for the managementof patients with acute chest pain due to possible ACS [1]. These guidelines have identified areas ofuncertainty 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.2. Investigation of the cost-effectiveness of multislice CT coronary angiography as a first-line test forruling out obstructive CAD in patients with suspected troponin-negative acute coronary syndromes.Evaluation of new troponin assays and other biomarkersThe draft NICE guidelines recommend measurement of troponin levels at 10–12 h after the onset ofsymptoms to accurately identify cases of MI. This is based upon evidence that troponin levels predictsubsequent risk of adverse outcome [7] and response to treatment [8], but do not achieve optimalsensitivity until 10–12 h after symptom onset [6]. However, delaying blood testing until 10–12 h aftersymptom onset is inconvenient for patients and often incurs additional health-care costs associatedwith hospital admission and/or observation. Various alternative strategies have been proposed for earlierdiagnosis of MI using combinations of biomarkers, measuring biomarker gradients and using newer, moresensitive troponin assays.178NIHR Journals Library