Long-term outcomes of SCOT HEART trial: Coming of age for coronary CT angiography?

SUMMARY

The Scottish Computed Tomography of the Heart (SCOT-HEART) trial, originally published in 2015, reported long-term (10-year) clinical outcome data.¹ This open-label, multicentre, randomized trial aimed to evaluate the impact of coronary computed tomography angiography (CCTA) on diagnostic certainty, treatment decisions, and major cardiovascular outcomes in stable chest pain patients. The trial randomized 4146 patients to standard care+CCTA (n=2073) versus standard care alone (n=2073).

The primary endpoint in the initial publication (2015) was the clinician’s certainty of diagnosing angina due to coronary artery disease (CAD) at 6 weeks, with the aid of the CCTA report in the intervention arm. The use of CCTA resulted in a change in diagnosis of CAD in about one-fourth of the patients enrolled in the CCTA arm, leading to a subsequent change in planned investigations (stress tests or invasive coronary angiogram). The authors reported that use of CCTA resulted in an increase in certainty (relative risk [RR] 1.79; 95% CI 1.62–1.96; p<0.0001) and a possible decrease in frequency (RR 0.93; 95% CI 0.85–1.02; p=0.129) of the diagnosis of angina due to CAD. At the initial 1.7 years of follow-up, there was a trend towards a decrease in rates of myocardial infarction (MI), though this was not statistically significant.²

In their prespecified 10-year analysis, the authors reported a significant reduction in the composite end-point of death due to CAD or non-fatal MI (6.6% of the patients in the CCTA arm compared to 8.2% in the standard care arm, HR 0.79, 95% CI 0.63–0.99; p=0.044). This benefit was driven by a reduction in non-fatal MI rates in the CCTA arm (4.3% v. 6%; HR 0.72; 95% CI 0.55–0.94; p=0.017). There was no difference in all-cause mortality or cardiovascular mortality between the two arms. Even though the initial publication of 2015 pointed towards increased rates of invasive angiography and coronary revascularization in the CCTA arm, there was no difference in the rates of coronary revascularization between the two arms at 10 years of follow-up (15.2% v. 15.3%; HR 1.00, p=0.99). The use of secondary prevention medical therapy was higher in the CCTA arm (56%) compared to the standard care arm (49%) (odds ratio [OR] 1.17; 95% CI 1.01–1.36; p=0.034). The authors concluded that, at 10 years of follow-up, CCTA-guided management of patients presenting with stable chest pain was associated with a reduction in the composite endpoint of death due to CAD or non-fatal MI. Identification of underlying CAD by CCTA results in long-term cardiovascular disease prevention in such patients.

COMMENTS

CAD is the leading cause of morbidity and mortality in India, causing susceptibility to premature mortality.³ Atherosclerosis pathobiology is characterized by a variable period of progressive subclinical disease leading to either luminal narrowing causing a demand-supply mismatch (exertional angina) or an acute plaque change (most commonly plaque rupture) that may lead to abrupt vessel closure and acute myocardial infarction.⁴ Broadly, there are two ways to diagnose CAD: to visualize the plaque causing luminal narrowing (anatomical tests like CCTA or invasive coronary angiography) or to detect the haemodynamic consequences of the luminal stenoses (stress or ischaemia testing like nuclear perfusion tests or exercise electrocardiography). Multiple observational studies have demonstrated excellent diagnostic accuracy of CCTA, with a sensitivity of 85%– 99% and a specificity of 64%–92%.⁵ In the landmark ISCHEMIA trial, 73% of the enrolled patients underwent blinded CCTA. An analysis of patients who subsequently underwent the gold standard invasive coronary angiography (ICA) confirmed a high concordance rate (>90%) between the two modalities.⁶ The SCOT-HEART trial was the first study to evaluate the role of CCTA in stable chest pain systematically and has the longest follow-up data available (now up to 10 years). The important learning point from the trial are discussed below.

It is important that approximately half of the MI occurred in patients with non-obstructive CAD at the baseline CCTA. Similar results were shown by the PROMISE trial, in which 54% of events in the CCTA arm occurred in those with non-obstructive disease at baseline.^7,8 This provides essential insight into the pathophysiology of CAD and positions CCTA as a unique test to diagnose such early disease, which is not possible with functional (stress) tests, the other common diagnostic modality used in such patients. This, in turn, leads to the earlier initiation of preventive medical therapy, which is often underutilized in the real world. Even in this trial, the percentage of patients on any antiplatelet drug or a statin was 35% and 45%, respectively, in the CCTA arm, and even lower in the standard care arm. This is low when compared to the percentage of patients (63%) with CAD detected on CCTA (obstructive 25% and non-obstructive 38%). It is important to note that higher rates of secondary prevention medications drove the benefits of the CCTA arm, as the revascularization rates were similar in the two arms.

There is a concern about increased ICA rates and subsequent revascularization in patients randomized to the CCTA arm, as pointed out by the initial 2015 publication of the SCOT-HEART and PROMISE trials.^7,9 However, overutilization of procedures is usually a health system-dependent issue and is more likely when interventions are incentivized, as in private healthcare models. Thus, CCTA may be an excellent tool for triaging patient risk as long as further therapy, especially revascularization, is guideline-based. The CCTA also provides an opportunity to identify lesions at a higher risk of causing acute coronary syndrome. These are plaques with low attenuation, positive remodelling, spotty calcification, and a napkin ring sign.^10,11

The main question thus remains when to use this important tool in our armamentarium. Should it be used routinely as a risk stratification tool? No, as exemplified by the FACTOR 64 trial done among people with diabetes, where routine CCTA evaluation did not confer any additional benefit over usual care.¹² CCTA’s benefits accrued only in the long term and only in non-fatal MI in the SCOT-HEART trial due to the low-risk population enrolled (<1% CAD death or non-fatal MI annually in both arms). There was a reduction in one MI at 10 years for every 58 patients enrolled, with no reduction in cardiovascular mortality. Thus, the optimum incremental value of CCTA would only happen if we use it in individuals with intermediate pre-test probability of having CAD, as all international guidelines advocate.^13,14

To conclude, the 10-year follow-up of the SCOT-HEART trial demonstrates that CCTA-guided management in patients with stable chest pain improves long-term outcomes primarily through better implementation of preventive medical therapies. CCTA provides excellent diagnostic accuracy to identify both obstructive and non-obstructive CAD, allowing initiation of evidence-based secondary prevention. Further large-scale trials in diverse populations, including Indian patients with higher CAD susceptibility, are warranted to confirm these findings and evaluate cost-effectiveness in varied healthcare settings.