title: Randomised Assessment of Treatment using Panel Assay of Cardiac markers--Contemporary Biomarker Evaluation (RATPAC CBE).
abstract: OBJECTIVE
  To test the diagnostic accuracy for detecting an acute myocardial infarction (AMI) using highly sensitive troponin assays and a range of new cardiac biomarkers of plaque destabilisation, myocardial ischaemia and necrosis; to test the prognostic accuracy for detecting adverse cardiac events using highly sensitive troponin assays and this range of new cardiac biomarkers; and to estimate the cost-effectiveness of using highly sensitive troponin assays or this range of new cardiac biomarkers instead of an admission and 10- to 12-hour troponin measurement.
  
  
  METHODS
  Substudy of the point-of-care arm of the RATPAC (Randomised Assessment of Treatment using Panel Assay of Cardiac markers) trial.
  
  
  METHODS
  The emergency departments of six hospitals.
  
  
  METHODS
  Prospective admissions with chest pain and a non-diagnostic electrocardiogram randomised to point-of-care assessment or conventional management.
  
  
  METHODS
  Blood samples taken on admission and 90 minutes from admission for measurement of cardiac markers [cardiac troponin I (cTnI), myoglobin and creatine kinase MB isoenzyme (CK-MB)] by point-of-care testing. An additional blood sample was taken at admission and 90 minutes from admission for analysis of high-sensitivity cTnI (two methods) and cardiac troponin T (cTnT), myoglobin, heart-type fatty acid-binding protein (H-FABP), copeptin and B-type natriuretic peptide (NTproBNP).
  
  
  METHODS
  1. Diagnostic accuracy compared with the universal definition of myocardial infarction utilising laboratory measurements of cardiac troponin performed at the participating sites together with measurements performed in a core laboratory. 2. Ability of biomarker measurements to predict major adverse cardiac events (death, non-fatal AMI, emergency revascularisation or hospitalisation for myocardial ischaemia) at 3 months' follow-up. 3. Comparison of incremental cost per quality-adjusted life-year (QALY) of different biomarker measurement strategies for the diagnosis of myocardial infarction.
  
  
  RESULTS
  Samples were available from 850 out of 1132 patients enrolled in the study. Measurement of admission myoglobin [area under the curve (AUC) 0.76] and CK-MB (AUC 0.84) was diagnostically inferior and did not add to the diagnostic efficiency of cTnI (AUC 0.90-0.94) or cTnT (AUC 0.92) measurement on admission. Simultaneous measurement of H-FABP and cTnT or cTnI did improve admission diagnostic sensitivity to 0.78-0.92, but only to the same level as that achieved with troponin measured on admission and at 90 minutes from admission (0.78-0.95). Copeptin (AUC 0.62) and NTproBNP (AUC 0.85) measured on admission were not useful as diagnostic markers. As a prognostic marker, troponin measured on admission using a high-sensitivity assay (AUC 0.73-0.83) was equivalent to NTproBNP measurement (AUC 0.77) on admission, but superior to copeptin measurement (AUC 0.58). From modelling, 10-hour troponin measurement is likely to be cost-effective compared with rapid rule-out strategies only if a £30,000 per QALY threshold is used and patients can be discharged as soon as a negative result is available.
  
  
  CONCLUSIONS
  The measurement of high-sensitivity cardiac troponin is the best single marker in patients presenting with chest pain. Additional measurements of myoglobin or CK-MB are not clinically effective or cost-effective. The optimal timing for measurement of cardiac troponin remains to be defined. Copeptin measurement is not recommended. H-FABP requires further investigation before it can be recommended for simultaneous measurement with high-sensitivity troponin in patients with acute chest pain.
  
  
  BACKGROUND
  ISRCTN37823923.
  
  
  BACKGROUND
  This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 15. See the HTA programme website for further project information.
authors.affiliation: Clinical Blood Sciences Laboratory, St George's Hospital, London, UK. paul.collinson@stgeorges.nhs.uk
authors.forename: P O
authors.initials: PO
authors.lastname: Collinson
authors.forename: D C
authors.initials: DC
authors.lastname: Gaze
authors.forename: P
authors.initials: P
authors.lastname: Thokala
authors.forename: S
authors.initials: S
authors.lastname: Goodacre
mesh_terms: D000208:Acute Disease; D015415:Biomarkers; D003362:Cost-Benefit Analysis; D052279:Creatine Kinase, MB Form; D004636:Emergency Service, Hospital; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins / Q000097:blood; D006020:Glycopeptides / Q000097:blood; D006801:Humans; D009203:Myocardial Infarction / Q000097:blood* / Q000378:metabolism; D017202:Myocardial Ischemia / Q000097:blood* / Q000378:metabolism; D009211:Myoglobin / Q000097:blood; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D019095:Point-of-Care Systems; D011379:Prognosis; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D019210:Troponin I / Q000097:blood*; D020107:Troponin T / Q000097:blood
chemical_list: D015415:Biomarkers; C493408:FABP3 protein, human; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins; D006020:Glycopeptides; D009211:Myoglobin; D010446:Peptide Fragments; D019210:Troponin I; D020107:Troponin T; C048197:copeptins; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D052279:Creatine Kinase, MB Form