Comparative effectiveness of initial computed tomography and invasive coronary angiography in women and men with stable chest pain and suspected coronary artery disease: multicentre randomised trial

Abstract

Objective: To assess the comparative effectiveness of computed tomography and invasive coronary angiography in women and men with stable chest pain suspected to be caused by coronary artery disease.

Design: Prospective, multicentre, randomised pragmatic trial.

Setting: Hospitals at 26 sites in 16 European countries.

Participants: 2002 (56.2%) women and 1559 (43.8%) men (total of 3561 patients) with suspected coronary artery disease referred for invasive coronary angiography on the basis of stable chest pain and a pre-test probability of obstructive coronary artery disease of 10-60%.

Intervention: Both women and men were randomised 1:1 (with stratification by gender and centre) to a strategy of either computed tomography or invasive coronary angiography as the initial diagnostic test (1019 and 983 women, and 789 and 770 men, respectively), and an intention-to-treat analysis was performed. Randomised allocation could not be blinded, but outcomes were assessed by investigators blinded to randomisation group.

Main outcome measures: The primary endpoint was major adverse cardiovascular events (MACE; cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke). Key secondary endpoints were an expanded MACE composite (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, transient ischaemic attack, or major procedure related complication) and major procedure related complications.

Results: Follow-up at a median of 3.5 years was available in 98.9% (1979/2002) of women and in 99.0% (1544/1559) of men. No statistically significant gender interaction was found for MACE (P=0.29), the expanded MACE composite (P=0.45), or major procedure related complications (P=0.11). In both genders, the rate of MACE did not differ between the computed tomography and invasive coronary angiography groups. In men, the expanded MACE composite endpoint occurred less frequently in the computed tomography group than in the invasive coronary angiography group (22 (2.8%) v 41 (5.3%); hazard ratio 0.52, 95% confidence interval 0.31 to 0.87). In women, the risk of having a major procedure related complication was lower in the computed tomography group than in the invasive coronary angiography group (3 (0.3%) v 21 (2.1%); hazard ratio 0.14, 0.04 to 0.46).

Conclusion: This study found no evidence for a difference between women and men in the benefit of using computed tomography rather than invasive coronary angiography as the initial diagnostic test for the management of stable chest pain in patients with an intermediate pre-test probability of coronary artery disease. An initial computed tomography scan was associated with fewer major procedure related complications in women and a lower frequency of the expanded MACE composite in men.

Trial registration: NCT02400229ClinicalTrials.gov NCT02400229.

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: funding from the EU-FP7 Framework Program. KFK, MBosserdt, PMH, NR, TB, PD, JRP, AE, CS, GS, FA, MG, JDD, ID, GD, EZ, CKępka, RV, MFrancone, MIS, FP, JK, RF, SS, CB, LS, BR, CKubiak, KSH, JMN, BM, TSJ, IB, FXV, LZ, VS, LZ, MC, MW, SK, IL, ET, MK, ANN, MM, GF, MP, VGR, TD, CD, BL, MFischer, BS, PES, MRatiu, SK, BGB, CKragelund, IR, SR, HCC, MBoussoussou, TE, RH, AEN, RH, SF, MMAM, KN, HD, MR, VW, ME, and MD received grants from the European Commission during the conduct of the study. KFK received grants and non-financial support from Rigshospitalet, University of Copenhagen, during the conduct of the study and grants from AP Møller og hustru Chastine McKinney Møllers Fond, the Danish Heart Foundation, the Danish Agency for Science, Technology and Innovation by the Danish Council for Strategic Research, and the Health Insurance Company Denmark and unrestricted research grants from Canon Medical Corporation and GE Healthcare outside the submitted work. PMH is a share holder of Neumann Medical Ltd outside the submitted work. NR is principal investigator for grants (no own salary) from the German Ministry of Education and Research (NAVICARE 01GY1911) outside the submitted work. TB has received grants from the Romanian Ministry of European Funds the Romanian Government and the European Union outside the submitted work. GS has received payments or honorariums from Amgen, Astra Zeneca, Bayer, Berlin Chemie Menarini Baltic, Clinical Financial Service, IQVIA, Novartis Baltics, Sanofi Aventis, and Servier Pharma; received support for attending meetings or travel from Servier and Novartis; and participated on data safety monitoring boards or advisory boards for Boehringer Ingelheim outside the submitted work. GS is fellow of the ECS and is involved in the Lithuanian Society of Cardiology, the Lithuanian Heart Association, and the Lithuanian Hypertension Society. MG has received payments or honorariums from Bayer, Siemens, Bracco, and the German Roentgen Society (DRG) to the institution outside the submitted work. MG is a member of the Scientific Committee of the ESCR and member of the Committee of the Working Group on Cardiovascular Imaging of the German Roentgen Society (DRG). EZ has received grants from the Deutsche Forschungsgemeinschaft (Radiomics in SPP 2177/1) outside the submitted work. JK has received speaker fees from GE Healthcare, Merck, Lundbeck, Bayer, Boehringer-Ingelheim, and Pfizer and personal fees for study protocol review from AstraZeneca and GE Healthcare outside the submitted work. JK is chair of the European Society of Cardiology guidelines on chronic coronary syndrome; the work is on a voluntary basis and only remuneration of travel expenses occurs. The University of Glasgow, which employs CB, who has no personal contracts and receives no payments outside of his employment, has received in kind support for research from AstraZeneca, grant and in kind support for research and R&D consultancy funding from Abbott Vascular, a grant from GSK, in kind support for research and R&D consultancy funding from HeartFlow, educational funding from Menarini, R&D consultancy funding from Novartis, and in kind support for research from Siemens, outside the submitted work; furthermore, the University of Glasgow received research funding from the British Heart Foundation (RE/18/6134217). BM has received personal fees from Biotronik, Medtronic, and Abbott and grants from Boston Scientific outside the submitted work. IB has received grants from the Romanian Ministry of European Funds, the Romanian Government, and the European Union outside the submitted work. MC has received direct payments from Abbott Vascular as lecturer, workshop participant as operator, and lecturer, Astra Zeneca as lecturer, and Boehringer Ingelheim, as well as payment to the institution from the National Science Center (Poland) outside the submitted work. MK has a granted patent (EP3157444B1) and pending patents (WO2015193847A1, WO2013060883A4). CD has received grants from the British Heart Foundation (Centre of Research Excellence RE/18/6/34217) during the conduct of the study. PES has received consulting fees from Novo Nordisk outside the submitted work. MR has received grants from the Deutsche Forschungsgemeinschaft (Radiomics in SPP 2177/1) outside the submitted work. TE has received personal fees from Abbott and Bayer outside the submitted work. MD has received grants from the Berlin Institute of Health (grant from Digital Health Accelerator), the German Research Foundation (grants from Radiomics Priority Programme: DE 1361/19-1 [428222922] and 20-1 [428223139] in SPP2177/1) and grants from the graduate program BIOQIC (GRK 2260/1 [289347353])) during the conduct of the study and grants from the Heisenberg Programme of the German Research Foundation, grants from fractal analysis of myocardial perfusion of the German Research Foundation, and a grant from the Berlin University Alliance (GC_SC_PC 27) outside the submitted work. In addition, MD holds a joint patent with Florian Michallek on dynamic perfusion analysis using fractal analysis (PCT/EP2016/071551 and USPTO 2021 10 991 109 approved) and is European Society of Radiology (ESR) research chair (2019-22) and elected ESR publications chair (2022-25); the opinions expressed in this article are the author’s own and do not represent the view of ESR; per the guiding principles of ESR, the work as research and publications chair is on a voluntary basis and only remuneration of travel expenses occurs. MD is also the editor of Cardiac CT, published by Springer Nature, and offers hands-on courses on computed tomography imaging (www.ct-kurs.de); institutional master research agreements exist with Siemens, General Electric, Philips, and Canon; the terms of these arrangements are managed by the legal department of Charité – Universitätsmedizin Berlin.

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