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Diagnosis of obstructive coronary artery disease using computed tomography angiography in patients with stable chest pain depending on clinical probability and in clinically important subgroups: meta-analysis of individual patient data

Robert Haase, Peter Schlattmann, Pascal Gueret, Daniele Andreini, Gianluca Pontone, Hatem Alkadhi, Jörg Hausleiter, Mario J Garcia, Sebastian Leschka, Willem B Meijboom, Elke Zimmermann, Bernhard Gerber, U Joseph Schoepf, Abbas A Shabestari, Bjarne L Nørgaard, Matthijs F L Meijs, Akira Sato, Kristian A Ovrehus, Axel C P Diederichsen, Shona M M Jenkins, Juhani Knuuti, Ashraf Hamdan, Bjørn A Halvorsen, Vladimir Mendoza-Rodriguez, Carlos E Rochitte, Johannes Rixe, Yung Liang Wan, Christoph Langer, Nuno Bettencourt, Eugenio Martuscelli, Said Ghostine, Ronny R Buechel, Konstantin Nikolaou, Hans Mickley, Lin Yang, Zhaqoi Zhang, Marcus Y Chen, David A Halon, Matthias Rief, Kai Sun, Beatrice Hirt-Moch, Hiroyuki Niinuma, Roy P Marcus, Simone Muraglia, Reda Jakamy, Benjamin J Chow, Philipp A Kaufmann, Jean-Claude Tardif, Cesar Nomura, Klaus F Kofoed, Jean-Pierre Laissy, Armin Arbab-Zadeh, Kakuya Kitagawa, Roger Laham, Masahiro Jinzaki, John Hoe, Frank J Rybicki, Arthur Scholte, Narinder Paul, Swee Y Tan, Kunihiro Yoshioka, Robert Röhle, Georg M Schuetz, Sabine Schueler, Maria H Coenen, Viktoria Wieske, Stephan Achenbach, Matthew J Budoff, Michael Laule, David E Newby, Marc Dewey & COME-CCT Consortium


To determine whether coronary computed tomography angiography (CTA) should be performed in patients with any clinical probability of coronary artery disease (CAD), and whether the diagnostic performance differs between subgroups of patients.

Prospectively designed meta-analysis of individual patient data from prospective diagnostic accuracy studies.

Medline, Embase, and Web of Science for published studies. Unpublished studies were identified via direct contact with participating investigators.

Prospective diagnostic accuracy studies that compared coronary CTA with coronary angiography as the reference standard, using at least a 50% diameter reduction as a cutoff value for obstructive CAD. All patients needed to have a clinical indication for coronary angiography due to suspected CAD, and both tests had to be performed in all patients. Results had to be provided using 2×2 or 3×2 cross tabulations for the comparison of CTA with coronary angiography. Primary outcomes were the positive and negative predictive values of CTA as a function of clinical pretest probability of obstructive CAD, analysed by a generalised linear mixed model; calculations were performed including and excluding non-diagnostic CTA results. The no-treat/treat threshold model was used to determine the range of appropriate pretest probabilities for CTA. The threshold model was based on obtained post-test probabilities of less than 15% in case of negative CTA and above 50% in case of positive CTA. Sex, angina pectoris type, age, and number of computed tomography detector rows were used as clinical variables to analyse the diagnostic performance in relevant subgroups.

Individual patient data from 5332 patients from 65 prospective diagnostic accuracy studies were retrieved. For a pretest probability range of 7-67%, the treat threshold of more than 50% and the no-treat threshold of less than 15% post-test probability were obtained using CTA. At a pretest probability of 7%, the positive predictive value of CTA was 50.9% (95% confidence interval 43.3% to 57.7%) and the negative predictive value of CTA was 97.8% (96.4% to 98.7%); corresponding values at a pretest probability of 67% were 82.7% (78.3% to 86.2%) and 85.0% (80.2% to 88.9%), respectively. The overall sensitivity of CTA was 95.2% (92.6% to 96.9%) and the specificity was 79.2% (74.9% to 82.9%). CTA using more than 64 detector rows was associated with a higher empirical sensitivity than CTA using up to 64 rows (93.4% 86.5%, P=0.002) and specificity (84.4% 72.6%, P<0.001). The area under the receiver-operating-characteristic curve for CTA was 0.897 (0.889 to 0.906), and the diagnostic performance of CTA was slightly lower in women than in with men (area under the curve 0.874 (0.858 to 0.890) 0.907 (0.897 to 0.916), P<0.001). The diagnostic performance of CTA was slightly lower in patients older than 75 (0.864 (0.834 to 0.894), P=0.018 all other age groups) and was not significantly influenced by angina pectoris type (typical angina 0.895 (0.873 to 0.917), atypical angina 0.898 (0.884 to 0.913), non-anginal chest pain 0.884 (0.870 to 0.899), other chest discomfort 0.915 (0.897 to 0.934)).

In a no-treat/treat threshold model, the diagnosis of obstructive CAD using coronary CTA in patients with stable chest pain was most accurate when the clinical pretest probability was between 7% and 67%. Performance of CTA was not influenced by the angina pectoris type and was slightly higher in men and lower in older patients.

PROSPERO CRD42012002780.
citation Haase R, Schlattmann P, Gueret P, Andreini D, Pontone G, Alkadhi H, Hausleiter J, Garcia M J, Leschka S, Meijboom W B, Zimmermann E, Gerber B, Schoepf U J, Shabestari A A, Nørgaard B L, Meijs M F L, Sato A, Ovrehus K A, Diederichsen A C P, Jenkins S M M, Knuuti J, Hamdan A, Halvorsen B A, Mendoza-Rodriguez V, Rochitte C E, Rixe J, Wan Y L, Langer C, Bettencourt N, Martuscelli E, Ghostine S, Buechel R R, Nikolaou K, Mickley H, Yang L, Zhang Z, Chen M Y, Halon D A, Rief M, Sun K, Hirt-Moch B, Niinuma H, Marcus R P, Muraglia S, Jakamy R, Chow B J, Kaufmann P A, Tardif J C, Nomura C, Kofoed K F, Laissy J P, Arbab-Zadeh A, Kitagawa K, Laham R, Jinzaki M, Hoe J, Rybicki F J, Scholte A, Paul N, Tan S Y, Yoshioka K, Röhle R, Schuetz G M, Schueler S, Coenen M H, Wieske V, Achenbach S, Budoff M J, Laule M, Newby D E, Dewey M, COME-CCT Consortium . Diagnosis of obstructive coronary artery disease using computed tomography angiography in patients with stable chest pain depending on clinical probability and in clinically important subgroups: meta-analysis of individual patient data. BMJ 2019; 365:l1945.
type journal paper/review (English)
date of publishing 12-06-2019
journal title BMJ (365)
ISSN electronic 1756-1833
pages l1945
PubMed 31189617
DOI 10.1136/bmj.l1945