Weekly Journal Scan: SCOT-HEART and the PROMISE of a long-term impact of coronary computed tomography angiography on the care of patients with suspected angina
Year: 2025
Type: article
Abstract: This comment refers to ‘Coronary CT angiography-guided management of patients with stable chest pain: 10-year outcomes from the SCOT-HEART randomised controlled trial in Scotland’, which was published in The Lancet, https://doi.org/10.1016/S0140-6736(24)02679-5. The Scottish Computed Tomography of the Heart (SCOT-HEART) was an open-label, parallel-group, randomized controlled trial (RCT) aimed at assessing the effect of coronary computed tomography angiography (CCTA) on the diagnosis, management, and outcome of patients with suspected angina due to coronary heart disease (CHD). Earlier analyses of the trial showed that, after 6 weeks, CCTA reclassified the diagnosis of CHD in 27% of patients, determining a change in planned investigations in 15% of cases, and a change in treatment in 23% of cases.1 At 5-year follow-up, the CCTA-guided management led to a reduction in the primary composite endpoint of CHD death or non-fatal myocardial infarction (MI) as compared with standard care alone, with similar coronary revascularization rates and higher use of preventive therapies.2 The present 10-year analysis of the SCOT-HEART trial reports the long-term management and outcomes of the 4146 patients (mean age, 57 years; 44% female; 11% diabetes) enrolled in the study between November 2010 and September 2014, and randomized to either CCTA plus standard of care (n = 2073) or standard of care alone (n = 2073).3 The mean 10-year cardiovascular (CV) risk score of the trial population was 17%. Among patients who underwent CCTA, median coronary artery calcium score was 20 Agatston units (interquartile range, IQR: 0–230), and obstructive coronary artery disease (CAD) was detected in 24% of cases. The primary outcome of this analysis was the incidence of CHD death or non-fatal MI. Secondary outcomes included all-cause death, CV death, CHD death, non-fatal MI, non-fatal stroke, coronary revascularization, and invasive coronary angiography. Data on preventive therapies were ascertained from the Prescribing Information System, a national database of each prescription dispensed in the Scottish community. Ten-year follow-up was completed in 96% of patients (median follow-up duration, 10.0 years; IQR, 9.3–11.0 years). The 10-year incidence of the primary composite outcome of CHD death or non-fatal MI was marginally significantly lower in the CCTA group than in the standard care group [6.6% vs. 8.2%, respectively; hazard ratio (HR), 0.79; 95% confidence interval (CI), 0.63–0.99; P = .044], entirely explained by a reduction in the incidence of non-fatal MI (4.3% vs. 6.0%, respectively; HR, 0.72; 95% CI, 0.55–0.94; P = .017). The incidence of CHD death was similar in the two groups (2.9% vs. 3.0%; HR, 0.97; 95% CI, 0.68–1.38). No differences were observed in all-cause death, CV death, or non-fatal stroke. The prescription rate of preventive therapies was higher in patients assigned to the CCTA group than in those assigned to the standard care group (56% vs. 49%, respectively). There was a higher use of statins, aspirin, other antiplatelet drugs, and angiotensin converting enzyme inhibitors (ACE-I) or angiotensin receptor blockers (ARBs) in patients assigned to the CCTA group as compared with those in the standard care group during the entire follow-up period. After 10 years, there was no difference in the rates of invasive coronary angiography between the CCTA group and the standard care group (28% vs. 27%, respectively). The coronary revascularization rate was also similar (15% in both groups). Coronary heart disease is the leading cause of morbidity and mortality worldwide, making early risk identification a key public health priority. Detecting high-risk patients enables targeted preventive treatments while avoiding unnecessary tests for others.4 However, assessing anginal symptoms remains challenging due to frequent atypical presentations. To guide diagnostic decisions, both European and US guidelines recommend pre-test clinical risk scores that incorporate age, sex, CV risk factors, and symptom severity.4,5 These scores, however, are based on retrospective data and may not fully reflect contemporary CVD prevalence, evolving risk factors, or the impact of modern therapies. In fact, in the current analysis of the SCOT-HEART trial, the baseline 10-year CV risk largely overestimated the actual rate of serious CV events. Non-invasive imaging is a valuable method for detecting CAD, enhancing risk stratification, and tailoring patient management. Due to its high sensitivity and specificity in detecting CAD, CCTA is increasingly being used to assess patients with stable chest pain.4,5 Large RCTs examining the impact of anatomy-based non-invasive diagnostic testing on CV outcomes have produced divergent results.1,2,6 In the PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain), CCTA did not improve outcomes compared to an initial standard care strategy, which included functional testing, although patients were followed up to ∼2 years and the study was not adequately powered to test a realistic superiority hypothesis on clinical outcomes.6 In contrast, the SCOT-HEART trial demonstrated significant changes in patient management with the addition of CCTA to standard care,1 which translated into a clinical benefit at mid-term (5 years) follow-up.2 The present analysis of the SCOT-HEART represents the longest follow-up of any CCTA trial to date, and shows that a CCTA-guided management strategy provides a persistent beneficial impact on non-fatal MI, with no effect on mortality, over a 10-year period in patients presenting with stable chest pain.3 This benefit was observed despite no significant differences in the rates of invasive coronary angiography or coronary revascularization at 10 years, after an initial increase in the early follow-up period (1–2 years) in the CCTA group. In contrast, the use of preventive therapies remained consistently higher in the CCTA-guided group even after a decade of follow-up. Being a purely diagnostic modality, CCTA cannot reduce CV events by itself, and the benefits observed might rather represent the result of a series of responses to the anatomical information provided, such as early coronary revascularization and increased prescription of evidence-based medications (e.g. statin, antiplatelet, and anti-hypertensive therapies) in higher-risk patients. Another unmeasured factor might be the increased patient awareness of CHD, which might have resulted in stronger commitment to healthy lifestyle changes and improved adherence to prescribed therapies.7 In this regard, the ongoing SCOT-HEART 2 trial is testing whether screening for CHD with CCTA is more clinically effective than CV risk scoring in guiding specific primary prevention recommendations.8 A major strength of the SCOT-HEART trial was its pragmatic design, allowing to recruit a broad population of patients aged 18–75 years referred by a primary-care physician to a dedicated cardiology clinic due to suspected stable chest pain, with very limited exclusion criteria (e.g. suspected acute coronary syndrome, or inability to undergo CT scanning due to allergy or renal failure). In line with this pragmatic approach, patients were not mandated to attend study-specific follow-up visits. Clinical outcomes were instead tracked using each patient’s unique Community Health Index (CHI) number from Public Health Scotland and National Records of Scotland. This is another strength of the trial, which allowed to maintain a very high follow-up rate (>96%) up to 10 years.3 With respect to the long-term efficacy of a CCTA-guided management strategy, it should be emphasized that the true effect size of this advantage remains statistically uncertain, as reflected by the wide 95% CI of the primary outcome reduction with an upper limit close to the null effect. Of note, the observed rate of the primary composite outcome (∼8% at 10 years) was much lower than what was assumed at the time of study design based on historical data (∼13% at 5 years). This suggests that the trial was largely underpowered to test the primary hypothesis. On the other hand, this lower-than-expected event rate is not entirely unexpected, as patient enrolment started more than two decades ago, and effective contemporary medical therapies have been meanwhile reducing the residual risk of patients with CHD. In addition, three out of four patients enrolled in the trial had normal coronary arteries or non-obstructive CAD, representing a relatively low-risk population. Due to the open-label design of the study, the potential for ascertainment bias cannot be completely ruled out. Another limitation of the trial is that patients were enrolled exclusively in Scotland, and no data on race and ethnicity were available, thus limiting the generalizability of the observed findings. A key consideration in the overall appraisal of a diagnostic strategy is cost-effectiveness, which was not addressed in this report, despite representing an important determinant of the most appropriate decision in the individual patient. Future investigations might integrate novel, more advanced methods, such as CCTA-derived fractional flow reserve,9 quantification of plaque burden and morphology,10 or pericoronary adipose tissue attenuation.11 Finally, advancements in CCTA technologies (e.g. latest-generation photon-counting CT scanners) and artificial intelligence, including radiomics, might further refine risk stratification of patients with CHD.12,13 While waiting for additional evidence from these emerging technologies and from the SCOT-HEART 2 trial, the 10-year follow-up analysis of the SCOT-HEART suggests a potential long-term clinical impact of a CCTA-guided management of patients with suspected angina due to CHD, the determinants of which remain substantially unknown. Further large-scale RCTs, adequately powered for clinical endpoints, are needed to confirm these findings and establish the true effect size and key determinants of the impact of a CCTA-guided management strategy. R.V. is consultant for Abbott Vascular and Medtronic; received lecturing fees from Abbott Vascular, Abiomed, Daiichi Sankyo, Edwards Lifesciences, Medtronic, Novartis, and Philips; and served as member of advisory boards for Amarin and Amgen. G.L. reports personal fees from Astra Zeneca, Boehringer Ingelheim, Novo Nordisk, Daiichi Sankyo, Sanofi, and Novartis; and served as member of advisory boards for Novonordisk and Novartis. G.L. reports grant support (to the Institution) for investigator-initiated research from the American Heart Association, the Italian Ministry of University and Research, and the Italian Ministry of Health (Grant: ‘Ricerca Corrente’).
Source: European Heart Journal
Authors: Rocco Vergallo, Giovanna Liuzzo
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4408845858