Add-On CTA Benefits Some—But Not All—with Stable Chest Pain

CT angiography (CTA) seemed to improve risk stratification as a second test after the exercise ECG in suspected stable angina, according to a post hoc analysis of the SCOT-HEART trial.

For individuals with abnormal or inconclusive results on stress testing, add-on CTA led to numerically fewer clinical events (3% vs 6% for ECG alone), reported Trisha Singh, BM, of the British Heart Foundation Centre for Cardiovascular Science at the University of Edinburgh, and co-authors.

Also, abnormal results of exercise ECG were linked with coronary revascularization at one year (hazard ratio 14.47, 95% CI 10.00-20.41) and coronary heart disease (CHD) death or non-fatal myocardial infarction (MI) at five years (HR 2.57, 95% CI 1.38-4.63) versus normal or inconclusive results, they stated in JAMA Cardiology.

With CTA, coronary revascularization at one year was predicted by:

• Obstructive coronary artery disease (CAD) versus no CAD: HR 1.70 (95% CI 1.47-1.97).
• Non-obstructive CAD versus no CAD: HR 1.17 (95% CI 1.04-1.33).

Singh’s group also found that coronary CTA had stronger ties to 5-year CHD death or non-fatal MI versus exercise ECG alone for obstructive CAD (HR 10.63, 95% CI 2.32-48.70) and non-obstructive CAD (HR 5.32, 95% CI 1.16-24.40).

They concluded that “Overall, an exercise ECG generally serves the clinician well for risk stratification and the selection of patients for coronary revascularization when results are abnormal, but for most patients without abnormal results of exercise ECG, coronary CT angiography provides additional information regarding the presence of CAD, the need for preventive treatments, and the potential for improved long-term clinical outcomes.”

However, the hypothesis-generating post hoc analysis had several limitations:

• There was potential for misclassification in the pragmatic trial as exercise ECGs were classified by the attending clinician, and there was no core laboratory or independent review of the test findings.
• Exercise ECG was not done for all patients and was not randomized, generating the potential for selection bias so there was no direct comparison of the effectiveness of functional versus anatomical testing.
• Patients who had coronary CTA had their treatments changed and received higher levels of secondary preventive therapy. As a result, the risk estimates for CTA were conservative.
• Subgroup sizes were small, which hampered the authors ability to make firm conclusions about identifying which patients may benefit most from secondary coronary CTA.

In an accompanying editorial, Pamela S. Douglas, MD, of the Duke Clinical Research Institute in Durham, North Carolina, expressed her main concern with the study, pointing out that the analysis “initially excluded the 21% of the SCOT-HEART cohort who did not undergo an exercise ECG, but then inexplicably did not exclude the 15% randomized to receive usual care plus CTA who did undergo CTA. This results in an as-tested analysis that excludes more than one-third of the randomized population, greatly weakening the power of randomization and introducing selection bias, making this essentially an observational study.”

Douglas also echoed many of the study limitations that Singh’s group noted, but acknowledged that while the results do not enthusiastically support the “addition of CTA for every patient with normal or inconclusive results of exercise ECG…the implication of this study is that exercise ECG alone, for most individuals, is not sufficient to optimize outcomes,” adding that the current analysis “gives weight to suggestions that CTA can best guide preventive care.”

In an accompanying viewpoint, Raymond J. Gibbons, MD, MSc, of the Mayo Clinic in Rochester, Minnesota, asked how fully generalizable the SCOT-HEART results are and if every patient with stable chest pain needed post-exercise ECG CTA.

The answer, he concluded, is no: “SCOT-HEART results are not generalizable to patient cohorts in other countries,” he wrote.

Gibbons offered multiple reasons for his negative assessment, including the fact that 9% of the randomized patients had known CHD, but SCOT-HEART did not report the adherence level of these patients to antiplatelets and statins at baseline and beyond. “The absolute benefit was greater in this high-risk subgroup,” he noted.

Also, the rate of revascularization in SCOT-HEART was lower than in the other trials, and Gibbons suggested that “both exercise test results and CTA [as a second test] by clinicians to identify the patients at the most risk potentially [led] to fewer revascularizations in the CTA group compared with trials of CTA as a first test.”

Finally, the SCOT-HEART investigators touted that “greater diagnostic certainty led to… increased use of… pharmacologic interventions in the coronary CTA group,” Gibbons pointed out. He countered that secondary prevention was recommended to all patients in the CTA group with obstructive or non-obstructive disease, but not for most patients in the standard care group regardless of the stress test results.

“Primary prevention was only recommended for patients in the standard care group who had a 10-year risk of 20% or more, which was the standard in the 2006 National Institute for Health and Care Excellence (NICE) lipid guidance when SCOT-HEART was designed,” he wrote. “Based on the mean 10-year risk of 17% in SCOT-HEART participants, no statin therapy would have been recommended in more than half of the patients receiving standard care. At 5 years, 40.5% of them were taking antiplatelet therapy, despite the NICE recommendation against routine antiplatelet therapy in primary prevention.”

However, NICE guidelines were updated in 2014 and lowered the threshold for primary prevention to a 10-year risk of ≥10% so “we do not know how many more patients in the standard care group should have been treated with statins, because their 10-year risk fell between 10% and 20%,” Gibbons stated.

He concluded that more post hoc analyses would mostly suggest which patient subsets have the greatest benefit with CTA and that “CTA remains a clinically useful second test after stress testing to evaluate stable chest pain in selected patients when the diagnosis of angina attributable to CHD remains unclear.”

The original open-label SCOT-HEART trial was conducted at 12 outpatient cardiology clinics in Scotland from 2010 to 2014 with over 4,000 patients. In 2018, the SCOT-HEART investigators reported that CTA resulted in fewer clinical events, but no increase in invasive coronary angiography or revascularization versus standard care alone.

The current analysis included 3,283 patients who underwent an exercise ECG (median age 57.0 years; 57.5% men). Of this group, 1,417 received add-on coronary CTA. Exercise ECGs were normal in two-thirds of cases.

Singh and co-authors reported that exercise ECG had a sensitivity of 39%, a specificity of 91%, a a positive predictive value of 58%, and a negative predictive value of 82% for detecting any obstructive CAD in patients who had subsequent invasive angiography.

Douglas suggested that perhaps the real value of the post hoc analysis lies in validating current guidelines that include exercise ECG as a first-line strategy in evaluating stable chest pain, and moving the cardiac community “beyond functional vs anatomical binary thinking, what if the best initial ’test’ in these stable outpatients is simply ensuring optimal use of statins and aspirin (the ostensible pathway of benefit of CTA in SCOT-HEART)?”

1. Coronary CT angiography (CTA) had a stronger association with 5-year coronary events compared with exercise ECG alone.

2. CTA remains a clinically useful second test after exercise ECG to evaluate stable chest pain in selected patients with an unclear diagnosis of coronary heart disease attributable to angina, but it is still unknown which patient subsets would gain the most with CTA.

Shalmali Pal, Contributing Writer, BreakingMED™

Cat ID: 102

Topic ID: 74,102,730,102,914,192,925