SCOT-HEART trial: reshuffling our approach to stable ischemic heart disease

Abstract

The role of diagnostic testing in triaging patients with stable ischemic heart disease continues to evolve towards recognizing the benefits of coronary CT angiography (CCTA) over functional testing. The SCOT-HEART (Scottish Computed Tomography of the HEART) trial highlights this paradigm shift finding a significant reduction of death from coronary heart disease or non-fatal myocardial infarction without a significant increased rate of invasive coronary angiography over a 5 year follow-up period when implementing CCTA with standard care vs standard care alone. The better negative predictive value and ability to identify nonobstructive coronary artery disease to optimize medical therapy highlight the benefits of a CCTA first strategy. With the advent of noninvasive fractional flow reserve (FFR) and widespread availability and ease of CT, CCTA continues to establish itself as a pivotal diagnostic exam for patients with stable ischemic heart disease. In this commentary, we review the SCOT-HEART trial and its impact on CCTA for patients with stable ischemic heart disease.

Introduction

Chest pain from stable ischemic heart disease (SIHD) affects millions of people every year requiring a large devotion of resources towards accurately diagnosing and treating ischemic heart disease driving the need to be more efficient. Diagnostic testing plays a crucial role in triaging those with true ischemic heart disease from other causes of chest pain and preventing unnecessary, possibly invasive exams and follow-up visits. Functional testing in the form of exercise electrocardiogram (ECG), myocardial perfusion imaging with single photon emission computed tomography (SPECT), stress echocardiogram, and positron emission tomography (PET) currently dominates this role. Interestingly, the accuracy and negative predictive value of functional testing have been shown to be inferior to coronary CT angiography (CCTA).¹ Furthermore, the inability of functional testing to detect nonobstructive coronary artery disease (CAD) impedes its prognostic value and warranty to exclude future ischemic events. No randomized control trial (RCT) has demonstrated the ability of CCTA to improve outcomes in patients with SIHD until the SCOT-HEART (Scottish Computed Tomography of the HEART) trial. In this commentary, we discuss the SCOT-HEART trial and its impact on the future of CCTA in evaluating stable ischemic heart disease.

SCOT-HEART Trial

The SCOT-HEART trial is an open-label multicenter trial that enrolled 4146 patients from ages of 18–75 who were referred to a cardiologist by their primary care physician for suspected chest pain related to SIHD.^2,3 All patients received a clinical assessment and 85% underwent exercise ECG. Clinicians were asked to record the likelihood of angina due to CAD, need for further diagnostic testing or invasive coronary angiography (ICA), and initial treatments at the end of the first visit. Patients were then randomized to standard care only group, where they received the ASSIGN risk assessment score, or CCTA with calcium scoring and standard care group. At 6 weeks, cardiologists reviewed the new results from the CCTA and ASSIGN risk assessment score and recorded changes to their initial diagnosis, recommendation for further testing, and treatment plan. The diagnostic certainty of angina from CAD at 6 weeks was the primary diagnostic end point.

At 6 weeks, both diagnostic certainty and frequency of diagnosis of CAD increased in the CCTA group.³ This changed the diagnosis of CAD in 27% of patients as opposed to only 1% assigned to standard care group resulting in cancelling 121 functional tests and 29 ICA and adding 94 ICA. Despite an initial increase, ICA rates were similar between the two groups at 5 years². In fact, after the initial year, less ICA occurred in the CCTA group. Rates of revascularization mirrored this pattern. Furthermore, referrals for ICA in the CCTA group corresponded to an increased rate of obstructive CAD and less negative exams compared to the standard care group. Optimal medical therapy (OMT) followed a similar pattern with 1 in 4 patients assigned to the CCTA group receiving an alteration in their medical therapy compared to just 1 in 20 patients in the standard care group. Based on CCTA, OMT targeted those with true coronary artery disease as opposed to risk assessment alone.

After 5 years, there was an overall reduction in the primary end point of coronary heart disease related death or non-fatal myocardial infarction (MI), primarily driven by the reduction in non-fatal MI in patients who underwent CCTA with standard care vs standard care alone (48 [2.3%] vs 81 [3.9%]; hazards ratio 0.59, 95% confidence interval 0.41 to 0.84; p = 0.004).²

Discussion

Many recent trials have compared CCTA to functional testing, which remains the first-line test for SIHD according to most guidelines. The EVINCI (Evaluation of Integrated Cardiac Imaging for the Detection and Characterization of Ischemic Heart Disease) trial demonstrated a superior accuracy and negative predictive value in CCTA over functional testing but failed to show a difference in outcomes of major adverse cardiac events (MACE).¹ Similarly, the PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) trial found CCTA to be non-inferior to functional testing in terms of outcomes over a 2-year follow-up period but was underpowered due to infrequent events.⁴ The SCOT-HEART trial was the first RCT to demonstrate a significant reduction in MACE, primarily driven by non-fatal MI when comparing CCTA with standard care.² A few factors to help explain this difference in outcomes should be mentioned. For instance, the SCOT-HEART trial had a higher prevalence of CAD and overall mortality when compared to other recent RCTs.⁵ A lower prevalence of CAD in trials completed in other health care systems such as the United States may be due to barriers preventing recruitment of patients, particularly those who may have a higher pretest probability of CAD.⁶ Furthermore, 85% of patients in the SCOT-HEART trial received an exercise ECG before proceeding to either the standard care or CCTA with standard care group.² Only 9% had stress myocardial perfusion imaging (MPI) in both groups.³ An exercise ECG is suboptimal compared to MPI. This may have reduced the diagnostic accuracy of the standard care group resulting in a larger difference in implementing OMT and potentially affecting clinical outcomes over 5 years.^5,7 In other countries such as the United States, stress MPI is more commonly used, which may suggest that the outcomes from the SCOT-HEART trial may not equate to other health care systems. The results, however, remain significant with impactful conclusions that continue to change our approach to SIHD. Even more so, data from the SCOT-HEART trial has produced numerous sub studies evaluating the secondary benefits of CCTA and various clinical perspectives of this well-designed study.^8–12

Prior to SCOT-HEART, trials focused on diagnosing obstructive disease for revascularization and OMT and its implications on reducing future MACE. Functional testing relies on identifying hemodynamically significant stenosis. When negative, this provides limited prognostic value. Interestingly, both PROMISE and SCOT-HEART trials found more than half of future MACE occurred in nonobstructive CAD, which would be negative on initial functional testing.^2,4,13 This highlights the importance of identifying and treating nonobstructive CAD to reduce future events.⁷

The CAPP (Cardiac CT for the Assessment of Pain and Plaque) and CRESCENT (CT vs Exercise Testing in Suspected Coronary Artery Disease) trials found increased diagnosis of CAD and use of preventive medications in the CCTA group.^14,15 Similarly, a study by Jorgense et al demonstrated increased use of preventative medications and ICA in the CCTA group.¹⁶ The anatomic information from CCTA has the advantage of identifying non-obstructive CAD more accurately than functional testing and clinical risk assessment alone, thus lowering the threshold for initiating OMT in a more efficient manner.¹³ Furthermore, there is the added benefit of identifying potentially vulnerable plaques and extent of CAD. A substudy of the SCOT-HEART trial by Williams et al demonstrated high-risk plaques and overall high calcium score to be associated with developing MACE.⁹ CCTA also identifies obstructive disease more accurately with a better negative predictive value than functional testing resulting in decreased nonobstructive coronary artery disease and negative exams on ICA.^2,4

Based on recent trials, CCTA is compelling for first line use in SIHD patients with the added benefit of prognostic value and initiating OMT in a timelier manner. The updated 2016 National Institute for Health and Care Excellence guidelines initiated CCTA as first line over functional testing. The recently updated 2019 European Society of Cardiology (ESC) guidelines for the newly termed chronic coronary syndromes has also adopted CCTA as first line along with functional imaging. According to these guidelines, CCTA should be the initial test in patients in a lower range of clinical likelihood for CAD while functional imaging best for a higher likelihood range.¹⁷ Of note, the new guidelines mentioned that the overall prevalence of CAD has decreased since the prior 2013 ESC guidelines with more patients in the lower risk category. Meanwhile, the American College of Cardiology (ACC)/American Heart Association (AHA) 2012 guidelines continue to use functional testing as first line.

Part of choosing which diagnostic imaging test to implement in a health care system should include a look at efficiency and cost. A recent comparison of various imaging strategies for SIHD found that a CT first strategy was the most cost-effective approach followed by MRI perfusion when the test is positive.¹⁸ This strategy is further supported by a recent trial showing non-inferiority of MRI perfusion to fractional flow reserve in conjunction with coronary angiography in terms of predicting events.¹⁹

An accurate method of risk assessment is also important to reduce costs. In a study by Baskaran et al using data from the SCOT-HEART trial, the updated Diamond Forrester score used in ESC and American College of Cardiology/American Heart Association guidelines were compared to CAD Consortium clinical score (CAD2) and CONFIRM risk score. CAD2, which incorporates risk factors and lipid panel, was the most preferred with better discrimination and reclassification than the other scoring systems.²⁰ Adopting better methods for risk stratification along with CCTA for first-line use could help improve efficiency in evaluating chest pain for SIHD.

The SCOT-HEART trial suggests that a reduction in MACE is possible with a CCTA driven algorithm by more accurately screening for obstructive CAD as a gatekeeper to revascularization and OMT but more importantly identifying non-obstructive CAD and initiating optimal medical therapy in a timelier manner. The potential cost savings and availability of CT also makes a CCTA first strategy in SIHD appealing for widespread adoption.