Cardiac MRI and SPECT Reduce Unnecessary Angiograms vs Guideline-Directed Care in Suspected CAD: CE-MARC2

In a randomized trial of three diagnostic strategies for patients with suspected coronary heart disease, the use of cardiac magnetic resonance (CMR) imaging significantly reduced the likelihood of unnecessary angiography performed within 12 months when compared with guideline-recommended clinical care. CMR also performed as well as myocardial perfusion imaging with single photon emission computed tomography (SPECT).

Presented today at the European Society of Cardiology Congress 2016 in Rome, Italy, and published simultaneously in the Journal of the American Medical Association, the Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease 2 (CE-MARC2) study showed that just 7.5% of patients with suspected angina underwent unnecessary angiography when CMR was used compared with 28.8% of patients treated according to guidelines outlined by the National Institute for Health and Care Excellence (NICE).

Of the patients who underwent nuclear testing with SPECT, 7.1% had a coronary angiogram that revealed no disease, a rate that was not statistically different compared with what was seen in the CMR-guided patients.

Presenting the results of CE-MARC2 to the media, lead investigator John Greenwood, MBChB, PhD (University of Leeds, England), said invasive angiography is commonly used early in the diagnostic pathway in patients with suspected coronary artery disease, sometimes needlessly. In one recent analysis of the US-based National Cardiovascular Data Registry (NCDR), for example, approximately 60% of the elective angiograms performed revealed no obstructive coronary heart disease, Greenwood reported.  

“The guidelines suggest we catheterize the highest-risk patients, but what we’ve shown here is that even when you use those [risk-stratification] models, perhaps we’re driving more patients to angiography than we really need to do and creating more unnecessary angiograms,” said Greenwood. “This is really important from a patient’s perspective. This trial has been designed very closely with patient involvement. One of the key things patients tell us is that they don’t want to go through an unnecessary invasive procedure.”

To TCTMD, Greenwood explained that the NICE guidelines for the investigation of stable chest pain recommend estimating the pretest probability of coronary heart disease. For low-risk patients (estimated risk between 10% and 29%), cardiac computed tomography should be performed to further define therapy. For those at intermediate risk (30% to 60% pretest probability of disease), functional testing with SPECT or CMR is recommended. The highest-risk patients can be considered for direct angiography.

No Difference in MACE Rates at 1 Year

The CE-MARC2 study tested the hypothesis that a CMR-directed strategy is superior to care directed by myocardial perfusion scintigraphy and by the NICE guidelines for reducing unnecessary coronary angiography. The trial was conducted at six UK hospitals and included 1,202 symptomatic patients with suspected coronary heart disease.   

In total, 265 patients underwent at least one coronary angiogram within 12 months of randomization. Of the 240 patients with care directed by the NICE guidelines, 42.5% underwent angiography. Of the 481 patients each in the CMR and scintigraphy groups, 17.7% and 16.2% had a coronary angiogram, respectively. When CMR was used to guide treatment, there was a 79% reduction in unnecessary angiograms compared with NICE-directed therapy (OR 0.21; 95% CI 0.12-0.34). Compared with myocardial perfusion scintigraphy, the use of CMR was not associated with a reduction in unnecessary angiography.

Importantly, there was no significant difference in the rate of major adverse cardiovascular events among the three diagnostic strategies. Over the course of the minimum follow-up of 1 year (median 15.8 months), at least one MACE occurred in 2.5% treated with the NICE-guideline strategy, 3.1% in the CMR group, and 3.1% in the scintigraphy arm. Annualized rates of MACE were 1.6%, 2.0%, and 2.0%, respectively.

To TCTMD, Greenwood said SPECT is the most widely used test for the assessment of myocardial ischemia in patients with suspected coronary artery disease, but noted that its diagnostic accuracy can vary and the test exposes patients to ionizing radiation. In the 2011 CE-MARC study published in the Lancet, a trial that included 752 patients with suspected angina and at least one cardiovascular risk factor, Greenwood and colleagues showed CMR was more accurate than SPECT for detecting stable coronary artery disease. Similarly, they also published long-term data showing that CMR was a better prognostic tool than SPECT in patients with suspected angina.

‘We’re Always Accused of Performing Too Many Angiograms’

Speaking with TCTMD, Kim Williams, MD (Rush University School of Medicine, Chicago, IL), the immediate-past president of the American College of Cardiology, said coronary angiography is reserved for patients in whom there is going to be suspected benefit. For example, a patient with a TIMI risk score of 3 or 4 is more likely to be sent directly to coronary angiography, while those with less risk are more likely be sent first for noninvasive imaging.

“From our point of view, it really is good to see a trial that tries to address whether or not we can reduce the problem that’s been reported in the US, which is the overutilization of cardiac catheterization,” said Williams. 

Still, Williams took a contrarian opinion of CE-MARC2, telling TCTMD that while the study showed no difference in MACE rates at 1 year among the three diagnostic strategies, there is a signal that the NICE-directed referrals to coronary angiography reduced clinical outcomes. He said the event rates—2.5% in the NICE guideline-directed arm versus 3.1% with functional testing—might be underpowered to detect between-group differences. “This looks like a potential type 2 error,” said Williams. “It looks like a significant difference that could have been shown if the study was larger.”

For Williams, the trend suggests the NICE guidelines might be better than CMR and SPECT at reducing clinical events. “Why would that be? It could be they’re loose enough to be inclusive,” he said. “So what do you get? You catch some potential major adverse cardiovascular events and catheterize some people who didn’t need it. It suggests it might be a better way of doing it.”

While he acknowledged such an interpretation of the data differs from that of the CE-MARC2 investigators, Williams would like to see a larger study performed to determine if clinical events differed with the diagnostic strategies.

European Society of Cardiology spokesperson Michael Haude, MD, PhD (Lukaskrankenhaus Neuss, Germany), told TCTMD that despite all the criticisms lobbied about overuse, angiography provides a very complete picture of the patient with suspected coronary artery disease.

“We are always accused of performing too many angiograms,” said Haude. “It’s something that exists in country to country, but at the end of day, what is angiography going to show? The definite presence or absence of coronary stenosis. You can identify lesions as significant if they pass a certain threshold and then you make a conclusion—either you intervene or you don’t intervene. You also have the opportunity to really evaluate a stenosis with add-on technology, such as fractional flow reserve.”

Moreover, Haude noted that most angiograms are performed transradially on an outpatient basis in a vast majority of cases, he said. While there is a risk for complications with coronary angiography, that risk is very low, he said. 

Clinical Recommendations in Europe and United States

To TCTMD, Haude said the European clinical guidelines recommend exercise testing first in patients with suspected coronary disease, followed by stress echocardiography. Although CMR provides better resolution and improved discrimination of wall-motion abnormalities than stress echocardiography, as well as a better assessment of ischemia, it is not widely available in all clinical centers, he said.

Raymond Gibbons, MD (Mayo Clinic, Rochester, MN), a past president of the American Heart Association, praised the CE-MARC2 investigators, saying the study was “well designed, conducted, and analyzed.” More importantly, he said the results provide important data for physicians on both sides of the Atlantic ocean.  

From the UK standpoint, the study supports the growing use of stress CMR for the detection of coronary artery disease over the existing NICE guidelines, while it also provides support for the increased use of myocardial perfusion imaging—either with SPECT, CMR, or stress echocardiography, which was not tested in CE-MARC2—in the United States.  

Importantly, Gibbons said, the trial also confirms data from previous studies suggesting that the traditional means of assessing the pretest probability of disease, which is based on patient age, gender, and chest pain symptoms, overestimates risk. For example, it showed that among patients who went directly to the cath lab for coronary angiography—those patients with a pretest probability of disease ranging from 60% to 90%—just 38% had coronary heart disease.

Related Stories:

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• CMR Outperforms SPECT at Predicting Long-Term Outcomes in Patients with Suspected Disease