CE-MARC 2: Cardiac MRI Avoids Unnecessary Angiograms in Suspected CAD

Patrice Wendling

August 30, 2016

ROME, ITALY — Cardiac magnetic resonance (CMR) imaging proved superior to national-guideline–directed care but no better than myocardial perfusion scintigraphy by single-photon-emission computed tomography (SPECT) for reducing unnecessary angiography in patients with suspected CHD in the randomized CE-MARC 2 trial[1].

Rates of unnecessary angiography within 12 months were 7.5% for CMR, 7.1% for SPECT, and 28.8% for care guided by National Institute for Health and Care Excellence (NICE) guidelines.

The data were presented here at the European Society of Cardiology (ESC) Congress 2016 and published simultaneously in the Journal of the American Medical Association.

Dr John Greenwood

"We have these guidelines that experts tell us seem to be the best way to manage patients, and here for the first time we've actually done a trial against them and shown we can outperform them," principal investigator Dr John Greenwood (University of Leeds, UK) Greenwood told heartwire from Medscape.

Patients were closely involved in the design of the trial and universally expressed a desire to avoid invasive testing, he noted. Moreover, patients around the world are managed according to guidelines based on older pretest likelihood models that overestimate CHD risk.

"That 60% of the patients who go to the cath lab don't have any obstructive coronary disease seems remarkable, in my opinion, when we've got advanced cross-sectional imaging techniques that can act as a gatekeeper to the cath lab," Greenwood added.

For the investigation of stable chest pain, NICE guidelines recommend cardiac computed tomography (CCT) for low-risk patients (pretest risk 10%–29%), functional testing with CMR or SPECT for intermediate-risk patients (pretest risk 30%–60%), and angiography for high-risk patients (pretest risk 61%–90%).

The 1202 patients in CE-MARC 2 had a CHD pretest likelihood of 10% to 90% (mean 49.5% based on the Duke clinical score). Within 12 months of randomization, 265 (22%) patients underwent at least one unnecessary angiogram.

In adjusted analyses, CMR reduced unnecessary angiograms by 79% compared with the NICE guidelines (odds ratio [OR] 0.21, 95% CI 0.12–0.34; P<0.001) but was not associated with a significant reduction compared with SPECT (OR 1.27, 95% CI 0.79–2.03; P=0.32).

In the CE-MARC trial, however, Greenwood and colleagues showed that CMR was shown to be more accurate for detecting stable CHD than SPECT, the world's most commonly used test to assess suspected CHD.

As for why CMR failed in the present trial to demonstrate superiority over SPECT as the investigators originally hypothesized, Greenwood said the pragmatic nature and power of the trial may have played a role.

Importantly, however, there was no difference between the three strategies in rates of disease detection or major adverse cardiovascular events (MACE).

MACE Data Questioned

During a median follow-up of 15.8 months, at least one MACE occurred in 2.5% of patients managed with NICE guidelines and 3.1% in both the CMR and SPECT groups. Adjusted hazard ratios for MACE were 1.37 (95% CI 0.52–3.57; P=0.52) for the CMR group vs the NICE guidelines group and 0.95 (95% CI 0.46–1.95; P=0.88) for the CMR group vs the SPECT group.

In examining the MACE data with heartwire , American College of Cardiology immediate past president Dr Kim Williams (Rush University School of Medicine, Chicago, IL) said there is an issue there that needs to be addressed because it appears there was actually a 37% increase in MACE using CMR vs NICE-guided care.

"That Kaplan-Meier plot in figure 3 is screaming type 2 statistical error, saying we really shouldn't say that there was no difference because it was probably underpowered," he added. "If this trend continued, if you had a larger population, you would say you'd save more lives, more events with the NICE guidelines, probably because the overutilization of coronary angiography catches an occasional person."

During the formal presentation, discussant Dr Udo Sechtem (Robert-Bosch Hospital, Stuttgart, Germany) expressed surprise that the event rate for the hard MACE end points of cardiovascular death and MI was only about 1% in each of the three groups (NICE 1.3%, CMR 1.0%, SPECT 0.8%) and questioned whether "the huge number of tests" in all three arms (n=478; n=520; n=524, respectively) was justified.

"I think that further research should be considered. This is such a low-risk cohort that I think that symptomatic treatment combined with preventive medication followed by revascularization in treatment failures would be an alternative as a first step, not go directly to testing," he said.

Sechtem said the pending economic analysis will be crucial in recommending one strategy over another but that "whatever we choose as a strategy, the event rate is so low that testing vs no testing at all needs to be studied."

Williams also called for additional research and suggested to heartwire that CMR should be compared with CT echocardiogram "because echo would have less expense and more speed, and CT does what I call the triple threat: anatomy, physiology, and morphology of coronary disease."

The trial was funded by grant and fellowships from the British Heart Foundation, the Leeds Teaching Hospital Charitable Foundation, and the National Institute for Health Research. Drs Greenwood reports no relevant financial relationships; disclosures for the coauthors are listed in the article. Sechtem and Williams reported no relevant financial relationships.

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