DISCHARGE Hailed as a Big Step Forward for CTA in Stable Chest Pain

There is no difference in the long-term risk of major adverse cardiovascular events between patients whose stable chest pain is initially evaluated with CT angiography compared with those sent for cardiac catheterization, according to results from a large, multicenter randomized trial.

Presented today at the 2022 European Congress of Radiology, and simultaneously published in the New England Journal of Medicine, the DISCHARGE trial showed that while MACE rates during long-term follow-up did not differ, invasive coronary angiography was associated with a significantly higher risk of procedure-related complications. 

“The data indicate that you can now use CT with sufficient confidence in select patients with stable chest pain and intermediate probability of coronary artery disease in whom you would have so far have done invasive coronary angiography,” lead investigator Marc Dewey, MD (Charité – Universitätsmedizin Berlin, Germany), told TCTMD. “The evidence for that is good with the trial. Such patients include, for instance, those where you have abnormal or inconclusive functional testing or where symptoms persist despite medical treatment. Those patients, so far, would undergo invasive coronary angiography if they had a high enough clinical probability [of obstructive CAD]. It’s probably a good idea to consider CT in such patients in the future.”

For Dewey, the study is “a paradigm shift in the assessment of stable chest pain.”

Marc Dweck, MBChB, PhD (University of Edinburgh, Scotland), who wasn’t involved in the study, said DISCHARGE should remind physicians that sending stable chest pain patients directly for cardiac catheterization without noninvasive testing beforehand is not the correct approach.

“It’s safe to use noninvasive imaging initially,” Dweck told TCTMD. “You reduce complication rates and you reduce the need for invasive procedures—that message is now clear. It adds to the growing strength of data supporting CT in the assessment of these patients. The question is now how we deliver CT on a bigger scale across Europe, the United States, and globally.”

Similarly, Jonathon Leipsic, MD (University of British Columbia/St. Paul’s Hospital, Canada), said the new study reemphasizes the role of noninvasive testing with CT angiography in patients with suspected CAD.

You can now use CT with sufficient confidence in select patients with stable chest pain and intermediate probability of coronary artery disease in whom you would have so far have done invasive coronary angiography. Marc Dewey

“This is another piece of the puzzle,” said Leipsic. “It builds data from smaller studies and pilot studies that have shown CT can really serve as a surrogate and inform invasive angiography. Obviously, we’ve seen trials like PLATFORM, CONSERVE, and other trials, but what’s quite amazing here is the lower event rate, driven by procedural complications not just related to PCI but invasive angiography. It’s something that again opens my eyes—invasive angiography is not a benign procedure. The idea of going to the cath lab without knowledge as to whether the patient has coronary disease is really in question based on these data.”   

In October 2021, the American College of Cardiology/American Heart Association published the first guidelines for the evaluation and diagnosis of acute and stable chest pain, giving a solid endorsement of CT. For the intermediate-probability patient without known CAD, coronary CT angiography is a class 1 recommendation for excluding atherosclerotic plaque and obstructive CAD (level of evidence A). The European Society of Cardiology also emphasizes noninvasive testing for patients with suspected CAD.

In the UK, the National Institute of Health and Care Excellence (NICE) has recommended CT angiography as the first-line diagnostic strategy in patients with new-onset chest pain since 2016.

Underutilization of CT Angiography

Despite the guideline recommendations, Dewey noted that CT remains relatively underutilized in the US and in Europe because no large multicenter trial so far has analyzed clinical outcomes after randomizing patients to CT or invasive coronary angiography. The reasons for its limited use also relate to national coverage decisions and reimbursement, he said. While cardiac catheterization remains the standard method of evaluating suspected CAD, roughly 50% to 60% of all cardiac catheterizations in Europe and the US do not find evidence of obstructive CAD requiring treatment. In Europe alone, it’s believed that 2 million invasive angiographies are performed each year where no obstructive CAD is found.

“It suggests there is a relevant proportion of overuse,” said Dewey.

Six years ago, the researchers published CAD-Man, a small, single-center study showing that CT angiography served as a gatekeeper for patients with atypical angina or chest pain referred for invasive coronary angiography. In that study, cardiac CT reduced the need for invasive angiography and led to a significantly greater diagnostic yield in those who did undergo cardiac catherization. It was also associated with fewer procedure-related complications. With that background, the DISCHARGE investigators wanted to determine the comparative effectiveness of CT and invasive angiography in the management of CAD to reduce the frequency of MACE.

The DISCHARGE study was a pragmatic, randomized trial conducted at 26 European centers. In total, 3,561 patients (56.2% women) with stable chest pain and an intermediate pretest probability of obstructive CAD (10% to 60%) were randomized to invasive angiography or CT angiography. Pretest probability of disease was assessed by age, sex, and type of chest pain (typical angina, atypical angina, nonanginal chest pain, and other chest discomfort).

The idea of going to the cath lab without knowledge as to whether the patient has coronary disease is really in question based on these data. Jonathon Leipsic

Over 3.5 years of follow-up, MACE occurred in 38 of 1,808 patients (2.1%) in the CT angiography arm compared with 52 events in 1,753 patients (3.0%) undergoing invasive angiography (HR 0.70; 95% CI 0.46-1.07). There was no significant difference in the risk of cardiovascular death, stroke, or MI, which were the components of the primary MACE endpoint. There was also no significant difference in patient-reported outcome measures, such as angina symptoms and health-related quality of life.

Major procedure-related complications occurred in 0.5% of patients undergoing CT angiography compared with 1.9% of those who had invasive angiography, a difference that was statistically significant (HR 0.26; 95% CI 0.13-0.55). These were events that included death, stroke, MI, or other complications leading to a hospital stay of at least 24 hours.  

‘It Will Likely Change Clinical Practice’

To TCTMD, Dewey believes DISCHARGE is a convincing study with excellent follow-up and adherence to study protocols. He also noted the trial was unique in that it included more women than men, a rarity among cardiovascular clinical studies.  

“It will likely change clinical practice and replace invasive testing with CT in a relevant proportion of patients with stable chest pain,” said Dewey. Still, there are caveats to that statement, he said, noting that researchers from the CoMe-CCT Consortium developed a method for the DISCHARGE trial to accurately assess the clinical probability of CAD. The DISCHARGE researchers plan to further evaluate this method of estimating pretest probability—which on purpose was based solely on patient history and clinical characteristics and did not include any functional testing—to see whether it can improve patient referral and indications for CT in routine clinical care.

“We don’t want to repeat the past and avoid examining patients who wouldn’t benefit because they had too little risk,” said Dewey.

For Leipsic, the study shows CT angiography as the first-line imaging strategy can “get the right patients to the cath lab.” Dweck, who was one of lead SCOT-HEART investigators, noted that while the clinical guidelines already recommend noninvasive testing for most patients with suspected chronic coronary syndromes, many centers still send patients directly for cardiac catheterization.

“It’s an important study,” said Dweck. “It supports the guidelines and challenges what is common practice in lots of places. Up-front CT cuts the amount of invasive caths needed by nearly 80%, and despite a lower subsequent rate of revascularization, there is no difference in outcomes between the two arms and no difference in symptomatic status.” 

One interesting aspect of DISCHARGE, said Dweck, is that the Kaplan-Meier event curves showed a separation between the two interventions in favor of CT angiography over time, but follow-up was shorter in DISCHARGE than that of the earlier SCOT-HEART trial. In the latter, follow-up to 5 years revealed that CT angiography was associated with a lower risk of cardiac death or MI compared with usual care, with a landmark analysis between 1 and 5 years tilting the results in favor of CT. For that reason, Dweck is hopeful that DISCHARGE investigators continue to follow patients to see if any significant difference in MACE arises.  

Some Questions Left Unanswered

In an editorial, Joseph Loscalzo, MD, PhD (Brigham and Women’s Hospital, Boston, MA), praises the DISCHARGE investigators for advancing the field, but adds that the trial also raises some questions. For example, more than one-third of patients had nonanginal chest pain, and if they had been excluded, would the results have changed? Secondly, just 25% of patients in each study arm had obstructive CAD, suggesting they might have been considered at low risk for obstructive CAD as opposed to intermediate risk. The ACC/AHA guidelines for stable chest pain state that low-risk patients receive no further testing/imaging but have medical therapy intensified instead.

Finally, Loscalzo questions whether the addition of functional testing, such as CT-derived estimates of fractional flow reserve (FFR-CT), or CT angiography-based quantification of plaque burden and lesion characteristics, could enhance the imaging test to better identify at-risk patients and improve outcomes.  

“No doubt, these and other questions will serve as the basis for future trials involving [coronary CT angiography] as its incorporation in the assessment of patients with stable angina continues to evolve,” writes Loscalzo.

Like Dweck, Leipsic said that one of the goals going forward to make sure that CT angiography is available for patients who need it. He noted that event rates in DISCHARGE were low, which emphasizes the importance of future studies aiming to identify patients at sufficiently high risk to warrant testing. The ongoing PRECISE trial is testing the optimal evaluation strategies in people with symptoms of CAD—the comparator arms include usual care with stress testing or cardiac catheterization vs FFR-CT—but will include as part of the intervention a subgroup of low-risk patients who will only be treated medically.

“Talking about resources and making sure people can get CT, one of the ways to do that is to make sure that people who don’t need any testing aren’t tested,” said Leipsic.     

Both Dweck and Leipsic praised the DISCHARGE investigators for conducting the trial, noting it was meticulously designed and well carried out. It was also a massive undertaking that was years in the works. Dewey, for his part, praised his collaborators, stressing that it included physicians from 18 European countries. “It’s amazing the cohesion of these PIs from different cultures,” he said. “I have to step up and say thank you.”