PROMISE Results Have Implications for Managed Care; May Change Guidelines, Put Pressure on Payers to Cover CTA

Patients who had computed tomography angiography (CTA) to evaluate their symptoms of heart disease fared about as well as patients who had functional testing for coronary artery disease (CAD), according to results of a large, federally funded trial presented March 14, 2015, at the 64th Annual Scientific Sessions of the American College of Cardiology.

The PROMISE study, one of the highlights of the meeting in San Diego, California, won praise from some for its “real world” focus, but also generated criticism for revealing the extent to which heart scans expose patients to radiation.

Both the study’s lead author and an editorial in the New England Journal of Medicine,^1,2 which simultaneously published the results, predicted updates to clinical guidelines and perhaps pres-sure on payers to cover CTA. A compan-ion economic study showed that CTA isn’t the healthcare cost-driver that some feared. This is good news, since 4 million Americans with health profiles similar to those in the study need tests each year for mid-range symptoms of heart disease. The NEJM editorial declared, “The cardiovascular imaging field is delivering comparative effective studies with results that are likely to change clinical practice.”²

PROMISE stands for Prospective Multicenter Imaging Study for Evaluation of Chest Pain. Top-line data for both the clinical and economic results were outlined together at a press conference, while the full studies were presented at separate late-breaking sessions. The National Heart, Lung, and Blood Institute funded the study, which cost $40 million, according to the Associated Press.³

From a managed care standpoint, results of the PROMISE trial are ground-breaking on several fronts. “No one’s done a clinical outcomes study of this size on imaging,” said Pamela S. Douglas, MD, of the Duke Clinical Research Institute, lead author of the clinical study. She predicted the findings will elevate CTA from a “maybe” to a “definitely appropriate” for physicians in clinical practice.

The study combines clinical findings with an economic analysis, which will be important for payers and policymakers. Daniel Mark, MD, also of the Duke Clinical Research Center, in presenting the economic data, said that CTA at the 2-year mark increased overall costs by less than $500 per patient, and the procedure “allows a more efficient use of downstream catheterization,” than functional tests.⁴

However, Eric Topol, MD, of the Scripps Clinic in La Jolla, California, posted a cri-tique of the NEJM editorial on Twitter and later told the Associated Press that the findings were “a bad reflection on American medicine” due to the radia-tion exposure patients received.³

The study involved 10,003 patients with no prior diagnosis of coronary ar-tery disease (CAD) but with symptoms that made physicians suspect heart dis-ease, such as chest pains or shortness of breath. Almost all had a risk factor asso-ciated with CAD, such as diabetes, high blood pressure, or a history of tobacco use. Half were randomly selected for CTA, which gives physicians a view of the arteries to determine whether they are narrowing. The others took an electrocardiogram (EKG), echocardiogram (ECG), or nuclear stress test; each of these tests evaluates the heart’s response to a stimulus. PROMISE represents the first time these 2 common tests have been compared head-to-head, an important mile-stone since current guidelines do not give either test priority.

Clinical Findings.

The mean age for pa-tients was 60.8 years, and 52.8% of pa-tients were women. Over a mean follow-up of 25 months, a primary end point a composite of death, myocardial infarction, hospitalization for unstable angi-na, or major procedural complications occurred in 164 of the 4996 patients (3.3%) who received CTA. Among pa-tients receiving functional testing, the primary end point occurred in 151 of the 5007 patients (3.0%) who received exer-cise EKG, nuclear stress testing, or stress ECG. The vast majority of the patients in this group (67.3%) received nuclear test-ing, with 22.5% receiving stress echocar-diography and 10.2% receiving exercise ECG. The difference in clinical outcomes between the 2 strategies was not statis-tically significant.

Some reporters questioned whether any positive conclusions could be drawn from these results, but both Douglas and Mark said that would be taking a narrow view. There were many results from the trial that researchers did not expect to see, such as the very low rate of cardiac events. Douglas pointed out that patients who had CTA were more likely to take medications that controlled the number of cardiac events.

Economic Findings.

Mark explained that for cardiologists, the arrival of CTA presented a holy grail they had always hoped for the opportunity to “see” what is happening in the arteries. And yet as the technology was being developed, he said, “Some of us have had second thoughts whether that’s such a good idea.” Would CTA end up being an expensive, overused technology that would lead to unnecessary radiation exposure and downstream costs, as physicians pursued additional testing of uncertain findings that turned up in this diagnostic test? Or would CTA lead to precision care, with only those needing revascularization opting for the procedure?

Such fears, as well as concerns about radiation exposure, have led to lukewarm reviews of CTA in clinical guidelines and among payers, although Mark noted that even among the functional tests, doctors in PROMISE overwhelmingly chose the high-tech, higher cost nuclear test option. Experts on hand noted that improvements to CTA are reducing the level of radiation exposure that patients experience.

Mark’s data estimated the overall cost of a CTA test at $404. For the functional tests, the cost of ECG with an exercise stress test was $514, while the cost of ECG with a pharmacologic stress test was $501. The estimate of a nuclear test was $946 and an exercise and pharmacologic stress testing was $1132. An ECG was the least expensive, at $174.

CTA increased the use of invasive catheterizations by 4% over function-al testing, and those in the CTA arm were twice as likely to have revascularization. However, Mark noted that as experts predicted, CTA does appear to do a better job of correctly identifying those patients in need of additional procedures: 51% of the CTA patients referred for catheterization underwent revascularization compared with just 39% of the functionally studied patients. In addition, fewer patients referred for catheterization via CTA were found to be negative for obstructive disease compared with those referred via a functional test an important point, because reducing unnecessary invasive tests is receiving increased scrutiny.

References

1. Douglas PS, Hoffman U, Patel MR, et al. Outcomes of anatomical versus functional testing for coronary artery disease [published online March 14, 2015]. N Engl J Med. doi:10.1056/ NEJMoa1415516.

2. Kramer CM. Cardiovascular imaging and outcomes—PROMISEs to keep [published online March 14, 2015]. N Engl J Med. doi:10.1056/ NEJMe1501924.

3. Marchione M. Study questions heart imaging; CT scans and older tests prove equally effec-tive for chest pain. Associated Press website. http://www.vancouversun.com/touch/story. html?id=10890578. Published and accessed March 14, 2015.

4. Mark DB, Anstrom K, Cowper P, et al. Eco-nomic comparison of anatomic versus functional diagnostic testing strategies in symptomatic patients with suspected CAD: results from the PROspective Multicenter Imaging Study for Evalu-ation of chest pain (PROMISE) trial. Presented at the 64th Annual Scientific Sessions of the American College of Cardiology; March 15, 2015; San Diego, CA.