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

DOI: 10.3310/hta17010 Health Technology Assessment 2013 Vol. 17 No. 1TABLE 24 Prognostic accuracy of biomarkers in troponin-negative patientsStudy Biomarker ThresholdBiomarkerpositiveBiomarkernegativeRRPonitz 2009 116 BNP Quartiles NR NR NR aBholasingh 2003 89 CRP > 0.3 mg/dl 8/135 3/236 4.7 (95% CI 1.3 to 17.3)Brennan 2003 91 CRP Quartiles NR NR NR bMenown 2003 113 CRP Quartiles NR NR NR cPonitz 2009 116 CRP Quartiles NR NR NR aEggers 2008 97 GRF-15 1200 ng/l 8/201 1/117 4.7 (95% CI 0.6 to 36.8)1800 ng/l 8/104 1/204 15.6 (95% CI 2.0 to 124)Ilva 2009 50 H-FABP 10.4 µg/l 6/28 11/159 3.1 (95% CI 1.2 to 7.7)Viswanathan 2010 121 H-FABP 6.48 µg/l 10/35 30/721 6.9 (95% CI 3.7 to 12.9)Menown 2003 113 Interleukin 6 Quartiles NR NR NR cCollinson 2006 48 IMA 85 kU/l 11/279 2/139 2.7 (95% CI 0.6 to 12.2)Apple 2007 87 MPO 125.6 µg/l 9/240 6/150 0.9 (95% CI 0.3 to 2.6)Apple 2011 88 MPO 633 pmol/l Unable toextractUnable toextractUnable to extract dBrennan 2003 91 MPO Quartiles NR NR NR bApple 2007 87 NT-pro-BNP < 75 years, 125 ng/l;≥ 75 years, 450 ng/l13/245 2/142 3.8 (95% CI 0.9 to 16.5)Lund 2003 107 PAPP-A 2.9 mIU/l 20/61 6/75 4.1 (95% CI 1.8 to 9.6)GRF-15, growth differentiation factor 15; NR, not reported.a Multivariate HR reported (see Table 23).b Multivariate OR reported (see Table 23).c Univariate OR reported (see Table 22).d Reported as 18.1% vs 5.0% (p < 0.002).only started to be used in patients presenting to hospital with acute pain many years after its diagnosticaccuracy for CAD had been evaluated in patients with stable chest pain.Diagnostic studies of computed tomographic coronary angiographyTable 25 shows the characteristics of the diagnostic studies that compared CTCA with a reference standardof ICA for CAD. The studies were relatively small (n = 31 to 113). Mean age varied from 53 to 62 years,and men outnumbered women in all studies. Most studies explicitly excluded patients with diagnosticECG changes. The threshold for diagnosing obstructive CAD was 50% stenosis in all studies, except for thestudy of Sato et al., 129 which used a threshold of 75% for both tests.Figure 27 shows the quality assessment and Figure 28 the methodological quality summary of diagnosticstudies of CTCA. Study quality was generally high, although blinding of interpretation of the index orreference standard test was unclear or absent in around half of the studies.Figure 29 shows the result of meta-analysis of CTCA diagnostic studies. The summary estimates ofsensitivity and specificity were 93% (95% predictive interval 61% to 99%) and 87% (16% to 100%),respectively. The highest sensitivity and specificity was achieved in the only study of 64-slice CT. 126 Twostudies 124,125 reported markedly lower specificity. The variation in specificity may be explained by artefact© Queen’s Printer and Controller of HMSO 2013. This work was produced by Goodacre et al. under the terms of a commissioning contract issued by the Secretary of Statefor Health. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journalsprovided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should beaddressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton SciencePark, Southampton SO16 7NS, UK.67