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Original Investigation |

Effect of Care Guided by Cardiovascular Magnetic Resonance, Myocardial Perfusion Scintigraphy, or NICE Guidelines on Subsequent Unnecessary Angiography Rates The CE-MARC 2 Randomized Clinical Trial

John P. Greenwood, PhD1; David P. Ripley, MBChB1; Colin Berry, PhD2; Gerry P. McCann, PhD3,4; Sven Plein, PhD1; Chiara Bucciarelli-Ducci, PhD5; Erica Dall’Armellina, PhD6; Abhiram Prasad, MD7; Petra Bijsterveld, MA1; James R. Foley, MBChB1; Kenneth Mangion, MD2; Mark Sculpher, PhD8; Simon Walker, MSc8; Colin C. Everett, MSc9; David A. Cairns, PhD9; Linda D. Sharples, PhD9; Julia M. Brown, MSc9 ; for the CE-MARC 2 Investigators
[+] Author Affiliations
1Division of Biomedical Imaging, Multidisciplinary Cardiovascular Research Centre, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, United Kingdom
2Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary, and Life Sciences, University of Glasgow, Glasgow, United Kingdom
3Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom
4NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, United Kingdom
5Cardiovascular Magnetic Resonance Unit, National Institute for Health Research Bristol Cardiovascular Biomedical Research Unit, Bristol Heart Institute, University of Bristol, Bristol, United Kingdom
6Acute Vascular Imaging Centre, Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom
7Cardiovascular Sciences Research Centre, St George’s, University of London, London, United Kingdom
8Centre for Health Economics, University of York, York, United Kingdom
9Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, United Kingdom
JAMA. 2016;316(10):1051-1060. doi:10.1001/jama.2016.12680.
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Importance  Among patients with suspected coronary heart disease (CHD), rates of invasive angiography are considered too high.

Objective  To test the hypothesis that among patients with suspected CHD, cardiovascular magnetic resonance (CMR)–guided care is superior to National Institute for Health and Care Excellence (NICE) guidelines–directed care and myocardial perfusion scintigraphy (MPS)–guided care in reducing unnecessary angiography.

Design, Setting, and Participants  Multicenter, 3-parallel group, randomized clinical trial using a pragmatic comparative effectiveness design. From 6 UK hospitals, 1202 symptomatic patients with suspected CHD and a CHD pretest likelihood of 10% to 90% were recruited. First randomization was November 23, 2012; last 12-month follow-up was March 12, 2016.

Interventions  Patients were randomly assigned (240:481:481) to management according to UK NICE guidelines or to guided care based on the results of CMR or MPS testing.

Main Outcomes and Measures  The primary end point was protocol-defined unnecessary coronary angiography (normal fractional flow reserve >0.8 or quantitative coronary angiography [QCA] showing no percentage diameter stenosis ≥70% in 1 view or ≥50% in 2 orthogonal views in all coronary vessels ≥2.5 mm diameter) within 12 months. Secondary end points included positive angiography, major adverse cardiovascular events (MACEs), and procedural complications.

Results  Among 1202 symptomatic patients (mean age, 56.3 years [SD, 9.0]; women, 564 [46.9%] ; mean CHD pretest likelihood, 49.5% [SD, 23.8%]), number of patients with invasive coronary angiography after 12 months was 102 in the NICE guidelines group (42.5% [95% CI, 36.2%-49.0%])], 85 in the CMR group (17.7% [95% CI, 14.4%-21.4%]); and 78 in the MPS group (16.2% [95% CI, 13.0%-19.8%]). Study-defined unnecessary angiography occurred in 69 (28.8%) in the NICE guidelines group, 36 (7.5%) in the CMR group, and 34 (7.1%) in the MPS group; adjusted odds ratio of unnecessary angiography: CMR group vs NICE guidelines group, 0.21 (95% CI, 0.12-0.34, P < .001); CMR group vs the MPS group, 1.27 (95% CI, 0.79-2.03, P = .32). Positive angiography proportions were 12.1% (95% CI, 8.2%-16.9%; 29/240 patients) for the NICE guidelines group, 9.8% (95% CI, 7.3%-12.8%; 47/481 patients) for the CMR group, and 8.7% (95% CI, 6.4%-11.6%; 42/481 patients) for the MPS group. A MACE was reported at a minimum of 12 months in 1.7% of patients in the NICE guidelines group, 2.5% in the CMR group, and 2.5% in the MPS group (adjusted hazard ratios: CMR group vs NICE guidelines group, 1.37 [95% CI, 0.52-3.57]; CMR group vs MPS group, 0.95 [95% CI, 0.46-1.95]).

Conclusions and Relevance  In patients with suspected angina, investigation by CMR resulted in a lower probability of unnecessary angiography within 12 months than NICE guideline–directed care, with no statistically significant difference between CMR and MPS strategies. There were no statistically significant differences in MACE rates.

Trial Registration  Clinicaltrials.gov Identifier: NCT01664858.

Figures in this Article


Place holder to copy figure label and caption
Figure 1.
Flow of Patients Through the Study of Noninvasive Imaging and Angiography Rates

ACS indicates acute coronary syndrome; CABG, coronary artery bypass grafting; CHD, coronary heart disease; NICE, National Institute for Health and Care Excellence; PCI, percutaneous coronary intervention.

aPatients may have received more than 1 test, in addition to or as an alternative to their strategy.

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Figure 2.
Effect of Specific Patient Characteristics on Results for CMR-Guided Care vs NICE Guidelines-Directed Care and MPS-Guided Care Among Patients With Suspected Coronary Heart Disease

CMR indicates cardiovascular magnetic resonance; ITT, intention to treat; NICE, National Institute for Health and Care Excellence; MPS, myocardial perfusion scintigraphy. Variables in the adjusted analysis for odds ratios included hypertension, ethnicity, and smoking status.

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Place holder to copy figure label and caption
Figure 3.
Time to First Major Adverse Cardiovascular Event After a Minimum of 12-Month Follow-up From Randomization Among Patients With Suspected Coronary Heart Disease (Median, 16 Months)

CMR indicates cardiovascular magnetic resonance; NICE, National Institute for Health and Care Excellence; MPS, myocardial perfusion scintigraphy. Hazard ratios from time to first major adverse cardiovascular event (and likelihood ratio test P values) were calculated by Cox proportional hazards modeling, adjusted for randomizing center, age category, sex, coronary heart disease pretest likelihood category, hypertension, race/ethnicity, diabetes, and smoking status. The median months of follow-up for the NICE guidelines group was 19.9 months (interquartile range [IQR], 12.1-24.1), 15.3 months (IQR, 12.2-24.2) for the CMR group, and 17.3 months (IQR, 12.1-24.2) for the MPS group.

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