Role of invasive angiography in suspected coronary artery disease: Results from the CE-MARC 2 Trial

Role of invasive angiography in suspected coronary artery disease: Results from the CE-MARC 2 Trial

Assessment, diagnosis and management of patients presenting with chest pain generate a significant workload for outpatient cardiology. Therefore, rapid-access chest pain clinics (RACPC) usually run by specialist nurses are ubiquitous across the national health service (NHS). NICE guidelines for chest pain of recent onset (CG95) published in 2010 - where the choice of investigation is based on Bayes theorem of ‘pre-test probabilities’ - have been established as the backbone of RACPC protocol.(1) Functional ischaemia assessment with non-invasive imaging is recommended for those patients with pre-test probability of 30–60% while invasive coronary angiography (ICA) is considered as the first-line diagnostic investigation for those with pre-test probability of 61-90%. However, a significant proportion of patients who received ICA had been found to have no significant obstructive coronary artery disease (CAD).(2–4) Therefore, there is a strong argument to reconsider the appropriateness of criteria for ICA in order to reduce unnecessary risks to patients and associated financial costs.

The Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease 2 (CE-MARC 2) study is a UK-based prospective, multicenter, randomised clinical trial, comparing the efficacy of stress cardiac magnetic resonance imaging (CMR), myocardial perfusion scintigraphy (MPS) and the standard NICE-guidance-directed care in reducing unnecessary ICA.(5) Patients with suspected coronary artery disease with pretest likelihood of 10 to 90% were included in the study. After screening nearly 14,000 patients, 1202 patients were randomised and allocated in 1:2:2 ratios to NICE, CMR and MPS groups, respectively. A positive result for non-invasive investigations resulted in ICA and fractional flow reserve (FFR) measurement. If FFR measurement was not feasible, quantitative coronary angiography (QCA) was performed. The primary end point of the trial was unnecessary coronary angiography occurring within 12 months, defined by a normal FFR (<0.8) or no significant CAD on QCA (percentage diameter stenosis of <70% in 1 view or <50% in 2 orthogonal views). Secondary end points were a composite of major adverse cardiovascular events (MACEs) and positive ICA rates. The incidence of primary end point (unnecessary ICA) for the CMR group was significantly lower than the NICE group (adjusted OR 0.21; 95% CI, 0.12-0.34; p < 0.001) but there was no significant difference between the CMR and MPS groups. As for secondary endpoints, there was no significant difference between all three groups for both positive angiography rates and annualised MACE rates. Sub-group analysis of high-pretest probability group (61-90%) revealed that functional imaging as a first-line strategy (CMR or MPS) resulted in a significantly lower odds of unnecessary ICA compared to the NICE group (OR 0.048; 95% CI, 0.02-0.10; p < 0.001).

 This novel well-designed trail has several important clinical implications. Firstly, it strongly suggests that in stable CAD, functional imaging-guided strategy significantly reduces the risk of unnecessary ICA without any significant penalty of increase in MACE rates. The choice of functional ischaemia assessment (CMR vs MPS) does not appear to have any significant impact on primary or secondary outcomes. Even though the European guidelines have been revised in 2013 to recommend a form of non-invasive imaging as a gatekeeper to the cardiac catherisation laboratory, this approach has not been reflected in the UK national guidelines.(6) In light of the findings from CE-MARC 2, it is now time to review and update our NICE guidelines for assessment of stable angina, which will have a major impact on configuration and downstream implications for cardiology services in the UK.

References

1.         Chest pain of recent onset: assessment and diagnosis | Guidance and guidelines | NICE [Internet]. [cited 2016 Sep 12]. Available from: https://www.nice.org.uk/guidance/cg95

2.         Hannan EL, Samadashvili Z, Cozzens K, Walford G, Holmes DR, Jacobs AK, et al. Appropriateness of diagnostic catheterization for suspected coronary artery disease in New York State. Circ Cardiovasc Interv. 2014 Feb;7(1):19–27.

3.         Patel MR, Peterson ED, Dai D, Brennan JM, Redberg RF, Anderson HV, et al. Low Diagnostic Yield of Elective Coronary Angiography. N Engl J Med. 2010 Mar 11;362(10):886–95.

4.         Patel MR, Dai D, Hernandez AF, Douglas PS, Messenger J, Garratt KN, et al. Prevalence and predictors of nonobstructive coronary artery disease identified with coronary angiography in contemporary clinical practice. Am Heart J. 2014 Jun;167(6):846–52.e2.

5.         Greenwood JP, Ripley DP, Berry C, et al. 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. JAMA [Internet]. 2016 Aug 29 [cited 2016 Sep 12]; Available from: http://dx.doi.org/10.1001/jama.2016.12680

6.         Members TF, Montalescot G, Sechtem U, Achenbach S, Andreotti F, Arden C, et al. 2013 ESC guidelines on the management of stable coronary artery disease. Eur Heart J. 2013 Oct 7;34(38):2949–3003.