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

Assessment of diagnostic and prognostic accuracyTABLE 23 Multivariate analyses reported in prognostic biomarker studies (continued)Study Biomarker ThresholdBiomarkerselection Analysis FindingYamashita NT-pro-BNP None: continuous None Multivariate OR2010 122 (with Tn)Kavsak 2009 103 PAPP-A Tertiles None Multivariate HR(with Tn)1.0 (95% CI 1.0 to 1.0)T1: ReferenceT2: 1.8 (95% CI 0.8 to 4.1)T3: 2.1 (95% CI 1.0 to 4.6)Lund 2003 107 PAPP-A 2.9 mIU/l Tn –ve Multivariate RR 2.6 (95% CI 1.1 to 6.5)Apple 2007 87 PIGF 17 ng/ml None Multivariate RR 0.7 (95% CI 0.3 to 1.5)Markovic PIGF 13.2 ng/l None Multivariate HR 2.1 (95% CI 1.1 to 4.2)2010 109Body 2011 46 P-selectin 60 µg/l None Multivariate OR(with Tn)1.8 (95% CI 1.1 to 3.1)Menown P-selectin 152 ng/ml TN –ve and2003 113 CK-MB –veMultivariate OR 4.0 (95% CI 1.0 to 15.7)CK-MB –ve, selected with normal CK-MB; eGFR, estimated glomerular filtration rate; GRF-15, growth differentiationfactor 15; PIGF, placental growth factor; Tn –ve, selected with normal troponin.some evidence that BNP, NT-pro-BNP, MPO and H-FABP can provide prognostic value when other predictorvariables are taken into account, whereas results for CRP and myoglobin were mixed.Table 24 shows whether or not the biomarker predicts MACEs in troponin-negative patients. Thisis probably the most useful analysis because troponin measurement is likely to be routine practicein most settings. Unfortunately, only a few studies reported this analysis so it is difficult to drawconclusions. However, there is some evidence that CRP, PAPP-A and H-FABP can predict MACEs introponin-negative patients.Summary of the findings of the prognostic biomarker reviewA variety of different biomarkers have been studied and an association shown between increased levelsand risk of MACEs, but it is not clear in most cases whether or not this adds useful prognostic informationbeyond that available from clinical assessment, ECG and troponin. There is some evidence that BNP,NT-pro-BNP, MPO and H-FABP can provide additional prognostic value beyond troponin, whereas CRP,PAPP-A and H-FABP can predict MACEs in troponin-negative patients. However, these findings are basedon a small number of heterogeneous studies and the utility of this prognostic value is unclear.Studies included in the computed tomographic coronary angiography andexercise electrocardiography reviewOverall, the literature searches identified 2667 citations. A flow chart describing the process of identifyingrelevant literature is shown in Figure 26. Of the titles and abstracts screened, 173 relevant full papers wereretrieved and assessed in detail. A total of 29 papers evaluating the diagnostic accuracy or prognosticperformance of CTCA or exercise ECG met the inclusion criteria. Studies excluded from the review are listedin Appendix 4. The principal reasons for exclusion were that the population was not suspected ACS andthe reference standard was not coronary angiography. The included studies consisted of eight diagnosticstudies of CTCA, 123–130 seven prognostic studies of CTCA, 131–137 no diagnostic studies of exercise ECG and13 prognostic studies of exercise ECG. 138–150 We also identified a prognostic study of CT CAC scoringwithout angiography. 151 Two of the prognostic studies of CTCA reported different follow-up for the samecohort, 132,133 and two of the prognostic studies of exercise ECG reported some patients in common. 138,140The lack of any diagnostic studies comparing exercise ECG with ICA is not surprising, as exercise ECG66NIHR Journals Library