Should NICE Guidelines Be Universally Accepted for the Evaluation of Stable Coronary Disease?

A Debate

Harvey S. Hecht; Leslee Shaw; Y.S. Chandrashekhar; Jeroen J. Bax; Jagat Narula

Disclosures

Eur Heart J. 2019;40(18):1440-1453. 

In This Article

What Should be the Future?

We need to first establish the goal of testing in any patient with suspected CAD—'detecting the presence of plaque (for preventive therapies) vs. identifying plaque that causes limitation in coronary blood flow (for revascularization and symptom relief) vs., detecting risk (for deploying a combination of medical and interventional/surgical therapies)' and plan our diagnostic strategies based on the answer to that question. Second, and more fundamentally, we need robust data that detecting any of these endpoints is meaningful and, more importantly, that intervening based on these endpoints changes outcomes. This is a critically deficient area in cardiology and trials like the ISCHEMIA Study will provide some clarity on this; many more such interventional trials are needed but possibly will never be done due to the logistics and expense.

It is evident that one test may not answer all these questions in many patients. Recognizing this, guidelines allow for layered testing in intermediate probability patients if the first test is not conclusive but a better and more efficient pathway is desirable. Since hybrid imaging has not been shown to be particularly efficient or useful,[42] a via media might be exploring novel strategies such as tiered testing as in the CRESCENT studies,[20,43] in which the presence or absence of coronary calcium is used to drive a higher level of testing and CTA drives CTP. A similar approach has been used with PET-CT in Europe where CTA is used to drive decisions about PET testing in the same session.[44] Finally, multi-parametric testing as in cardiac magnetic resonance (simultaneously obtaining information about morphology, function, flow and viability) might help efficient testing in centres with such expertise.

Our understanding of CAD and what a stenosis means is changing. Individual angioplasty trials have not clearly shown that fixing a severe stenosis (which is what the majority of non-invasive testing detect) changes hard outcomes in stable CAD, although a recent pooled data analysis demonstrated a reduction in myocardial infarction after invasive FFR-guided percutaneous coronary intervention.[45] The PCI advantage in angina resolution is temporary and replicable with good medical therapy. Although most severe stenoses are FFR positive, it has become clear that high-risk plaque composition plays an important role in contributing to positive FFR findings in the absence of severe stenosis. Mild to moderate stenoses may progress prior to acute events or may rupture before progression to significant obstruction; these non-obstructive culprit lesions are not likely to be detected by functional testing. Computed tomography might have an advantage in this area—CT best identifies high-risk plaque non-invasively but is only modestly predictive of future events;[40] one needs to evaluate thousands of plaque to detect those with multiple high-risk features and the positive predictive value (PPV) is low.[40,46] High-risk plaques may show dynamicity[47] with the eventual outcome that 10 years out, patients with and without high-risk plaque seem to have similar total number of events.[40] In addition, there is no strong evidence as yet that treating based on plaque morphology is useful but there are some exciting trials in the offing. The simple quantification of CAC is reasonably predictive of adverse hard events and the advantage of CTA testing over CAC alone is not likely to be easily demonstrable for hard events. Future studies such as ISCHEMIA[28] will clarify the role of non-invasive testing for the inducible ischaemia endpoint, while others in the planning stage might help clarify testing for high-risk plaque. It is good to keep an open mind about the role of testing for CAD. As Bertrand Russell said—the demand for certainty is one which is natural to man but is nevertheless, an intellectual vice.

Although there are fundamental differences between the United Kingdom National Health System, European medical provisions, and the United States, there are no differences in the nature of CAD, the quality of the practice of cardiology, and the expertise and judgement of those whose interpretation of the data resulted in the decision to recommend CTA as the first line diagnostic test for stable chest pain in patients without confirmed CAD. While CT derived FFR may currently be limited in availability by its single company origin and pricing, work station and machine learning based alternatives may significantly broaden its utilization, and CTP is available wherever CTA is performed. However, more clinical trial data may be needed for societal acceptance, as suggested by the most recent European guideline on myocardial revascularization.[50]

Updated United States and European stable chest pain guidelines are due and should be incorporating the voluminous comparative literature pertaining to CTA and functional testing that has recently become available. Cost effectiveness analysis is also likely to weigh substantially in the future recommendations. Furthermore, the ability of CTA to identify non-obstructive disease and high-risk plaque, and prognostic and preventive implications thereof should heavily support the application of this modality[48] (Take home figure). Whether the combination of CTA and CT derived FFR can replace invasive ICA and invasive FFR for revascularization decision-making, as suggested by the SYNTAX III Revolution trial,[49] remains to be determined.

Take Home Figure.

NICE guideline: the scales of computed tomography angiography evidence. Equipoise between pro and con (above) until addition of computed tomography derived fractional flow reserve and high-risk plaque tips the balance in favour of computed tomography angiography driven NICE guideline by providing functional input, improved specificity, and even better risk assessment (below). CTA, coronary computed tomographic angiography; CT-FFR, fractional flow reserve derived from CTA; HRP, high-risk plaque.

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