title: High-sensitivity troponin assays for the early rule-out or diagnosis of acute myocardial infarction in people with acute chest pain: a systematic review and cost-effectiveness analysis.
abstract: BACKGROUND
  Early diagnosis of acute myocardial infarction (AMI) can ensure quick and effective treatment but only 20% of adults with emergency admissions for chest pain have an AMI. High-sensitivity cardiac troponin (hs-cTn) assays may allow rapid rule-out of AMI and avoidance of unnecessary hospital admissions and anxiety.
  
  
  OBJECTIVE
  To assess the clinical effectiveness and cost-effectiveness of hs-cTn assays for the early (within 4 hours of presentation) rule-out of AMI in adults with acute chest pain.
  
  
  METHODS
  Sixteen databases, including MEDLINE and EMBASE, research registers and conference proceedings, were searched to October 2013. Study quality was assessed using QUADAS-2. The bivariate model was used to estimate summary sensitivity and specificity for meta-analyses involving four or more studies, otherwise random-effects logistic regression was used. The health-economic analysis considered the long-term costs and quality-adjusted life-years (QALYs) associated with different troponin (Tn) testing methods. The de novo model consisted of a decision tree and Markov model. A lifetime time horizon (60 years) was used.
  
  
  RESULTS
  Eighteen studies were included in the clinical effectiveness review. The optimum strategy, based on the Roche assay, used a limit of blank (LoB) threshold in a presentation sample to rule out AMI [negative likelihood ratio (LR-) 0.10, 95% confidence interval (CI) 0.05 to 0.18]. Patients testing positive could then have a further test at 2 hours; a result above the 99th centile on either sample and a delta (Δ) of ≥ 20% has some potential for ruling in an AMI [positive likelihood ratio (LR+) 8.42, 95% CI 6.11 to 11.60], whereas a result below the 99th centile on both samples and a Δ of < 20% can be used to rule out an AMI (LR- 0.04, 95% CI 0.02 to 0.10). The optimum strategy, based on the Abbott assay, used a limit of detection (LoD) threshold in a presentation sample to rule out AMI (LR- 0.01, 95% CI 0.00 to 0.08). Patients testing positive could then have a further test at 3 hours; a result above the 99th centile on this sample has some potential for ruling in an AMI (LR+ 10.16, 95% CI 8.38 to 12.31), whereas a result below the 99th centile can be used to rule out an AMI (LR- 0.02, 95% CI 0.01 to 0.05). In the base-case analysis, standard Tn testing was both most effective and most costly. Strategies considered cost-effective depending upon incremental cost-effectiveness ratio thresholds were Abbott 99th centile (thresholds of < £6597), Beckman 99th centile (thresholds between £6597 and £30,042), Abbott optimal strategy (LoD threshold at presentation, followed by 99th centile threshold at 3 hours) (thresholds between £30,042 and £103,194) and the standard Tn test (thresholds over £103,194). The Roche 99th centile and the Roche optimal strategy [LoB threshold at presentation followed by 99th centile threshold and/or Δ20% (compared with presentation test) at 1-3 hours] were extendedly dominated in this analysis.
  
  
  CONCLUSIONS
  There is some evidence to suggest that hs-CTn testing may provide an effective and cost-effective approach to early rule-out of AMI. Further research is needed to clarify optimal diagnostic thresholds and testing strategies.
  
  
  BACKGROUND
  This study is registered as PROSPERO CRD42013005939.
  
  
  BACKGROUND
  The National Institute for Health Research Health Technology Assessment programme.
authors.affiliation: Kleijnen Systematic Reviews Ltd, York, UK.
authors.forename: Marie
authors.initials: M
authors.lastname: Westwood
authors.affiliation: Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Thea
authors.initials: T
authors.lastname: van Asselt
authors.affiliation: Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Bram
authors.initials: B
authors.lastname: Ramaekers
authors.affiliation: Kleijnen Systematic Reviews Ltd, York, UK.
authors.forename: Penny
authors.initials: P
authors.lastname: Whiting
authors.affiliation: Health Economics and Decision Science Group, School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UK.
authors.forename: Praveen
authors.initials: P
authors.lastname: Thokala
authors.affiliation: Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Manuela
authors.initials: M
authors.lastname: Joore
authors.affiliation: Kleijnen Systematic Reviews Ltd, York, UK.
authors.forename: Nigel
authors.initials: N
authors.lastname: Armstrong
authors.affiliation: Kleijnen Systematic Reviews Ltd, York, UK.
authors.forename: Janine
authors.initials: J
authors.lastname: Ross
authors.affiliation: Institute of Health Policy and Management, Erasmus University Rotterdam, Rotterdam, The Netherlands.
authors.forename: Johan
authors.initials: J
authors.lastname: Severens
authors.affiliation: School for Public Health and Primary Care (CAPHRI), Maastricht University, Maastricht, The Netherlands.
authors.forename: Jos
authors.initials: J
authors.lastname: Kleijnen
mesh_terms: D000328:Adult; D002637:Chest Pain / Q000175:diagnosis* / Q000191:economics / Q000209:etiology; D003362:Cost-Benefit Analysis; D017721:Hospital Costs / Q000706:statistics & numerical data; D006801:Humans; D009203:Myocardial Infarction / Q000097:blood / Q000175:diagnosis* / Q000191:economics; D019209:Troponin C / Q000097:blood* / Q000191:economics
chemical_list: D019209:Troponin C