Outcomes Research in Review

Can Cardiovascular Magnetic Resonance, Myocardial Perfusion Scintigraphy, or NICE Guidelines Prevent Unnecessary Angiography?

Greenwood JP, Ripley DP, Berry C, et al. Effect of care guided by cardiovascular magnetic resonance, myocardial perfusion scintigraphy, or NICE guidelines on subsequent uncecessary angiography rates: The CE-MARC 2 randomized clinical trial. JAMA 2016;316:1051–60.



Study Overview

Objective. To assess whether noninvasive functional imaging strategies reduced unnecessary angiography compared with UK national guidelines–directed care.

Design. 3–parallel group, multicenter randomized clinical trial using a pragmatic comparative effectiveness design.

Setting and participants . Participants were patients from 6 UK centers (Leeds, Glasgow, Leicester, Bristol, Oxford, London) age 30 years or older with suspected angina pectoris, a coronary heart disease (CHD) pretest likelihood of 10% to 90%, and who were suitable for revascularization. They were randomly assigned at a 1:2:2 allocation ratio to the UK NICE (National Institute for Health Care Excellence) guidelines or to care guided by the results of cardiovascular magnetic resonance (CMR) or myocardial perfusion scintigraphy (MPS).

Main outcome measures . The primary outcome of the study was protocol-defined unnecessary coronary angiography occurring within 12 months, defined by a normal FFR (fractional flow reserve) > 0.8, or quantitative coronary angiography (QCA) showing no percentage diameter stenosis ≥ 70% in 1 view or ≥ 70% in 2 orthogonal views in all vessels 2.5 mm or more in diameter within 12 months. Because of the study design, this included any unnecessary angiography occurring after a false-positive test result, patients with high CHD pretest likelihood sent directly to coronary angiography in the NICE guidelines group, and imaging results that were either inconclusive or negative but overruled by the responsible physician.

Secondary endpoints included positive angiography rates, a composite of major adverse cardiovascular events (MACEs: cardiovascular death, myocardial infarction, unplanned coronary revascularization, and hospital admission for cardiovascular cause), and procedural complications.

Main results . Among 2205 patients assessed for eligibility between 23 November 2012 and 13 March 2015, 1202 patients (55% of eligible) were recruited and allocated to NICE guidelines–directed care ( n = 240), or management by CMR ( n = 481) or MPS ( n = 481). While there were no statistical differences between the 3 groups in terms of baseline characteristics, the study population had a substantial burden of cardiovascular risk factors: 150 patients (12.5%) had diabetes, 458 patients (38.1%) had hypertension, 702 patients (58.4%) were past or current tobacco users, 483 patients (40.2%) had dyslipidemia, and 651 patients (54.2%) had a family history of premature CHD. All patients were symptomatic, with 401 patients (33.4%) reporting typical chest pain and 801 patients (66.6%) reporting atypical chest pain as their primary symptom. Overall, 265 patients (22.0%) underwent at least 1 coronary angiogram and 10 patients underwent 2 angiograms.

The number of patients with invasive coronary angiography after 12 months were as follows: 102 of the 240 patients in the NICE guidelines group (42.5% [95% confidence interval {CI} 36.2%–49.0%]), 85 of the 481 patients in the CMR group (17.7% [95% CI 14.4%–21.4%]), and 78 of the 481 patients in the MPS group (16.2% [95% CI 13.0%–19.8%]). The primary endpoint of unnecessary angiography occurred in 69 patients (28.8%) in the NICE guidelines group, 36 patients (7.5%) in the CMR group, and 34 patients (7.1%) in the MPS group. Using CMR group as reference, adjusted odds ratio (AOR) of unnecessary angiography for CMR group vs. NICE guidelines group was 0.21 (95% CI 0.12–0.34, P < 0.001), and the AOR for CMR group vs. the MPS groups was 1.27 (95% CI 0.79–2.03, P = 0.32).

For the secondary endpoints, positive angiography was observed in 29 patients (12.1% [95% CI 8.2%–16.9%]) in the NICE guidelines group, 47 patients (9.8% [95% CI 7.3%–12.8%]) in the CMR group, and 42 patients (8.7% [95% CI 6.4%–11.6%]) in the MPS group, overall P = 0.36. Annualized MACE rates ware 1.6% in the NICE guidelines group, 2.0% for the CMR group, and 2.0% for the MPS group. Adjusted hazard ratios for MACE were 1.37 (95% CI 0.52–3.57, P = 0.52) for the CMR group vs. NICE guidelines group and 0.95 (95% CI 0.46–1.95, P = 0.88) for the CMR group vs. the MPS group.

Conclusion. In patients with suspected CHD, investigation by CMR or MPS resulted in lower probability of unnecessary angiography within 12 months of care than using the NICE guideline–directed care. There was no difference in adverse outcomes as measured by MACE by using NICE guidelines, CMR, or MPS.


Coronary heart disease is a leading cause of morbidity and mortality worldwide. Despite the advancement in noninvasive imaging and recommendations in international guidelines, invasive coronary angiography is still commonly used early in diagnostic pathways in patients with suspected CHD [1]. Previous studies demonstrated that majority of patients presenting with chest pain will not have significant obstructive coronary disease; a large US study reported that approximately 60% of elective cardiac catheterizations found no obstructive CHD [2]. Thus, avoiding unnecessary angiography should reduce patient risk and provide significant financial savings. Current guidelines for investigation of stable chest pain rely on pretest likelihood of CHD. These pretest likelihood models can overestimate CHD risk, resulting in the increase in probability of invasive coronary angiography [1,3].

The current study by Greenwood et al investigated whether CMR-guided care is superior to MPS or NICE guidelines–directed care in reducing the occurrence of unnecessary angiography within 12 months. Overall, rates of disease detection based on positive angiogram were comparable for the 3 strategies. In addition, there was no difference in adverse events as measured by a composite of MACE.

While this was an excellently performed multicenter study, there were several major limitations. First, the study population was predominately white northern European (92% were classified ethnically as white), and therefore the results may not translate to other populations. Second, the NICE guidelines for estimation of high-risk CHD changed after initiation of the study due to overestimation, and recent guidelines have adopted a recalibrated risk model [4,5]. Finally, MACE is not a proxy for a missed diagnosis or treatment. It remains debatable whether revascularization for stable angina has prognostic benefit over optimal medical therapy.

Applications for Clinical Practice

This multicenter randomized clinical trial provides strong evidence to use either cardiovascular magnetic resonance–guided care or myocardial perfusion scintigraphy–guided care instead of NICE guidelines–directed care for symptomatic patients with suspected CHD in reducing unnecessary angiography.

—Ka Ming Gordon Ngai, MD, MPH

Next Article: