SCOT-HEART: CT Angiography Linked to Less CAD Death, Nonfatal MI

MUNICH — Adding CT coronary angiography (CTCA) to standard care in patients with stable chest pain leads to a significant reduction in rates of death from coronary heart disease (CHD) or nonfatal myocardial infarction (MI) after 5 years, without increasing coronary intervention rates, researchers conclude.

The Scottish COmputed Tomography of the HEART Trial (SCOT-HEART) involved more than 4000 patients with stable chest pain who were randomly assigned to CTCA plus standard care or standard care alone and followed up for almost 5 years.

The results, presented here at the European Society of Cardiology (ESC) Congress 2018 and published simultaneously August 25 in the New England Journal of Medicine, suggest that performing CTCA during diagnostic testing was associated with a 41% reduction in the combined primary endpoint: rates of death from CHD and nonfatal MI.

David E. Newby, MD, British Heart Foundation Professor of Cardiology at the University of Edinburgh, United Kingdom, who led the study, said that there was, however, no overall difference in rates of coronary angiography or coronary revascularization, with CTCA even linked to a reduction in intervention after 1 year of follow-up.

He also showed data indicating that patients who had CTCA alongside standard care were more likely to be initiated on statin therapy than those who had standard care alone, suggesting that greater awareness of a patient's condition led to better care.

At the end of his presentation, Newby asked the audience whether CTCA should be "the noninvasive test of choice."

He told theheart.org | Medscape Cardiology afterward that in his view, the answer was unequivocally "yes." He pointed that the other available tests "all predict risk, et cetera, but does it make a difference to the patient?"

When a patient comes to the clinic, he said, "They want to know two things: Is this pain anything to do with my heart, and, if it is, am I going to have a heart attack?"

Newby explained that CTCA "addresses those two questions," whereas, with a stress test, the answers will be, "well, probably you have and maybe you will."

He said that their results showed that CTCA "made a difference," adding: "Show me another imaging test that is shown to reduce the rates of MI. There isn't one. So why aren't we using it first line?"

Newby believes that one barrier to more widespread use of CTCA is that of access, but that can be overcome with the allocation of more resources to the technique, as it was for primary angioplasty when it was recommended for ST-segment elevation MI.

Consequently, the current findings will encourage the provision of more resources to allow more CTCA scans to be performed, he said. "It's resource application; we need to stop doing other things and plough it into doing CTs."

SCOT-HEART, PROMISE

Previously published results from SCOT-HEART showed that, while the addition of CTCA to standard care resulted in a change in diagnosis and treatment in a quarter of patients, there was no significant change in the rate of CHD death or nonfatal MI, Newby noted in his presentation.

Similarly, findings from the PROspective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) study also showed a nonsignificant reduction in death or nonfatal MI.

Newby pointed out, however, that these analyses were based on a follow-up period of approximately 2 years.

During the same period, the SCOT-HEART study also indicated there was a nonsignificant increase in coronary revascularization rates with CTCA, while the PROMISE study found a significant increase in procedures at 90 days after CTCA (P < .001).

For the current analysis, the team conducted a prespecified 5-year assessment of the impact of CTCA on CHD death or nonfatal MI, invasive coronary angiography and coronary revascularization rates, and the prescription of preventive therapies.

Newby reminded the audience that in SCOT-HEART, patients were randomly assigned to CTCA plus standard care or standard care alone, after undergoing diagnostic investigations and having had a treatment plan developed.

Following CTCA, or a cardiovascular risk assessment using the ASSIGN Score for patients in the standard care–alone arm, all participants had their treatment plans re-examined, followed by a 6-week review with an angina questionnaire.

Of the 2073 patients from across Scotland who were allocated to the CTCA plus standard care group, complete 5-year data were available for 2047, alongside complete data on 2033 of 2073 patients assigned to standard care alone.

With the patients followed up for a median of 4.8 years, a total of 20,254 patient-years of data were available for analysis.

Overall, the patients had a mean age of 57 years, and 56% were male. Just over half (53%) were current smokers or ex-smokers.

Most (84%) patients had a normal electrocardiogram, and 62% of patients who underwent stress echocardiography had a normal result, with a further 16% inconclusive.

Newby reported that patients who had CTCA plus standard care were significantly less likely to experience the primary endpoint of CHD death or nonfatal MI than those who had standard care alone, at a hazard ratio of 0.59 (95% confidence interval [CI], 0.41 - 0.84; P = .004).

When the researchers performed a post hoc analysis of events after 1 year of follow-up, so as to better capture the true impact of CTCA, the differences were even greater, at a hazard ratio of 0.53 vs standard care alone (95% CI, 0.36 - 0.78; P = .001).

Returning to the main analysis, Newby showed that there were no overall significant interactions between CTCA and outcomes when they looked at subgroups based on age, sex, 10-year cardiovascular risk, anginal symptoms, prior CHD, and diabetes.

However, patients undergoing CTCA plus standard care did appear to be significantly less likely to experience the primary endpoint if they had a 10-year cardiovascular risk of 15 or less, symptoms indicating possible angina or no prior CHD, or were male.

Looking at individual endpoints, Newby showed CTCA plus standard care was associated with a significant reduction in nonfatal MI compared with standard care alone, at a hazard ratio of 0.60 (95% CI, 0.41 - 0.87; P = .007).

This appeared to be driving the reduction in the primary endpoint because there was no significant association between CTCA and rates of cardiovascular and noncardiovascular death.

Overall, there was no significant difference in rates of invasive coronary angiography or coronary revascularization between the two study arms, although the post hoc post–1-year analysis suggested a reduction in rates of both procedures with CTCA plus standard care.

Specifically, CTCA plus standard care was associated with a hazard ratio for invasive coronary angiography vs standard care alone of 0.70 (95% CI, 0.52 - 0.95; P = .002), while that for coronary revascularization was 0.59 (95% CI, 0.38 - 0.90; P = .015).

Newby also said that performing CTCA alongside standard care was associated with a significant increase in the use of statins during all years of follow-up (P < .0001).

He concluded that CTCA-guided managed reduces 5-year CHD death or nonfatal MI, which appears to be "attributable to better targeted preventative therapies and coronary revascularization."

Moreover, he said that "early increases in invasive coronary angiography and coronary revascularization are offset by lower rates beyond 1 year."

In an accompanying editorial, Udo Hoffmann, MD, MPH, from Massachusetts General Hospital, Harvard Medical School, Boston, and James E. Udelson, MD, from Tufts Medical Center, Boston, welcomed the findings.

"The data from the SCOT‐HEART trial suggest that management that is informed by results of CTA is associated with a lower rate of myocardial infarction than management that is informed by results of stress ECG testing," they write.

"There may even be the potential for a lower incidence of myocardial infarction when CTA data are used than when data from any functional test are used."

Noting also their own analysis of the PROMISE trial, they add: "The more general message from these trials is that the information provided by a diagnostic test can resonate therapeutically beyond making a correct diagnosis of coronary artery disease and that clinicians should aggressively pursue preventive measures to achieve the best outcomes possible while minimizing daily symptoms."

Too Good to Be True?

Approached for comment, Andrew Foy, MD, assistant professor of medicine and public health sciences at Penn State College of Medicine, Hershey, Pennsylvania, who was not involved in the study, was not so enthusiastic.

He told theheart.org | Medscape Cardiology: "My initial reaction was that the results were too good to be true."

Foy said that he has criticized the trial in the past for being an outlier, in particular because patients in the CTCA arm underwent stress testing.

"CTCA wasn't the first test, it was really the second test, after patients got a stress test," he explained. "So SCOT-HEART was never a trial of CTCA vs stress testing, it was a trial of stress testing plus CTCA vs stress testing alone, and it was an inferior stress modality, which was exercise electrocardiography."

The issue of the impact of exercise testing on the results was also raised during the postpresentation discussion, but Newby said that the researchers used it "more as a functional test of the symptoms rather than to diagnose coronary disease."

Foy believes, however, that this was not the major issue with the trial. "The bigger surprise to me," he said, "was the significant risk reduction, which I don't think anybody would have necessarily anticipated, given that this was a trial of imaging in a primary prevention population, more or less."

Pointing out that he and his colleagues recently published a meta-analysis of CTCA trials, he said that this one "is a little different because it had such a long follow-up relative to the standard CTCA trials…but to me this is just not really a believable result, because I can't postulate a mechanism for an imaging study that reduced events by 40%."

Foy explained: "At end of the day, 97 more patients ended up being treated with preventive therapies and so if we consider a standard number needed to treat for aspirin, statins, whether it's primary or even secondary prevention, we're somewhere in the ballpark of 30 to 50, some would even say 100."

"So how many events would that have reduced in those 97 patients? Two or three?" he asked.

"We're talking about 40 events in the trial. Where did that come from? To me — I don't know if it's luck, if it's issues with adjudication, given that this is open-label with no adjudication committee — but I just can't believe that it's being driven by management changes from CTCA."

Foy said the findings don't change his thinking on CTCA very much. "When it comes to assessing patients with potential ischemic chest pain, I still prefer functional stress testing for making the correct diagnosis."

He added that CTCA "leads to significant overuse of the cath lab and of stenting compared to functional stress testing alone, and so being somebody that tries to avoid overuse as much as possible, I still will be doing functional stress testing in patients who I suspect have ischemic chest discomfort when it's appropriate to order any testing."

Foy said that the "sweet spot" for CTCA is "those rare cases of patients that are hospitalized, that have troponin elevation, who tend to be young and in whom I don't think it's probably due to a coronary disease."

"But I really don't use it very often and I think it leads to overuse, if it's going to be the first test for patients with suspected coronary disease," he concluded.

SCOT-HEART was funded primarily by a grant from the Chief Scientist Office of the Scottish Government with supplementary support from grants from the British Heart Foundation, and from Ediburgh and Lothians Health Foundation Trust and the Heart Diseases Research Fund. Edinburgh Imaging (University of Edinburgh), the Edinburgh Clinical Research Facility, the Glasgow Clinical Research Facility, and the Clinical Research Centre Tayside are supported by National Health Service (NHS)Research Scotland. The Royal Bank of Scotland funded the provision of a 320-slice multidetector computed tomographic scanner for NHS Lothian and the University of Edinburgh. Newby reports grants from Siemens outside the submitted work. Disclosures for other coauthors can be found at www.nejm.org . Hoffmann reports grants from HeartFlow, outside the submitted work; Udelson reports nonfinancial support and other from Heartflow, outside the submitted work.

European Society of Cardiology (ESC) Congress 2018. Abstract 443. Presented August 25, 2018.

N Engl J Med. Published online August 26, 2018. Full text

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