March 14th, 2015

Has CT Angiography Lived Up to Its Early Promise?

Computed tomographic angiography (CTA) enjoyed an explosion of growth over the past decade or more, fueled by enthusiasm for its ability to deliver speedy, high-resolution images of the coronary arteries. Many anticipated that CTA would prove its worth and justify its expense and radiation dose. As explained by one cardiologist, Duke University’s Dan Mark, with CTA “only the patients who needed revascularization would actually go to the cath lab and the rest would avoid it,” leading to a reduced use of invasive tests, fewer unnecessary revascularizations, fewer false positives, and, therefore, significant economic advantages. Many years later, however, there is still little agreement about CTA and how it should be used in the diagnosis and management of people with chest pain.

Results of the NHLBI-supported Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE), presented at the American College of Cardiology meeting in San Diego and published simultaneously in the New England Journal of Medicine, provide the best evidence yet for the evaluation of CTA. The trial included 10,003 patients with chest pain randomized to CTA or functional exercise testing, consisting of either a standard exercise ECG test, a nuclear stress test, or stress echocardiography.

After two years the trial showed that CTA brought no improvement to the long-term outcome of the patients. The primary endpoint of the trial — the composite endpoint of death, MI, hospitalization for unstable angina, or major procedural complication — occurred in 3.3% of patients in the CTA group versus 3% in the control group. The results were consistent across different subgroups of patients.

A major goal of these procedures is to reduce highly invasive cardiac catheterizations. But within the first three months, 12.2% in the CTA group and 8.1% of the control group underwent cardiac catheterization. However, fewer patients in the CTA group who underwent catheterization were found to have no obstructive disease (27.9% in the CTA group and 52.5% in the control group).

The low number of events in the trial “probably reflects an excellent prognosis for patients with similar, new-onset, stable chest pain in real-world settings in which contemporary testing methods are used,” the authors wrote. “Showing a difference in patient outcomes with different testing strategies given this excellent midterm prognosis would require a large incremental test effect driving differences in downstream care or an extremely large study sample.”

“These findings highlight a substantial opportunity to improve the selection of patients for noninvasive testing beyond currently accepted approaches,” they wrote.

Although PROMISE didn’t provide a definitive answer to the role of CTA in clinical practice, it also didn’t give a broad endorsement to CTA, which makes doing CTA “less necessary,” said John Ryan. It “slows down the CTA train a little.”

In an accompanying editorial, Christopher Kramer terms the result a “tie” and asks how it will alter clinical practice.

Dan Mark, a PROMISE investigator who presented the results of the PROMISE economic substudy, said that CTA “may not be the ‘holy grail’ of diagnostic testing once hoped for” but that more liberal use “will improve some aspects of care without causing a major new economic burden on the health care system.” After more than two years of followup the use of CTA resulted in only a small, nonsignificant increase in cost (less than $500) and resulted in fewer patients going on to have an invasive cardiac catheterization with normal findings, he said.

The principal investigator of PROMISE, Pam Douglas, also at Duke, told CardioExchange that although they had expected CTA to lead to more catheterizations and revascularization procedures, “we were surprised by how much it improved the cath yield (rate of finding obstructive CAD at cath).” She said that CTA “is now proven to be a very viable alternative to functional testing. It should be considered as a first-line tool for patients with stable chest pain.”

To read our interview with Dr. Douglas about PROMISE click here, and to view all of our coverage from the ACC meeting, go to our ACC.15 Headquarters page.








5 Responses to “Has CT Angiography Lived Up to Its Early Promise?”

  1. Update:

    During the discussion section Douglas said that she thought the results of PROMISE could have a big impact on guidelines. She said that the guideline recommendation for CTA could shift from an uncertain (2B) recommendation to a 2A or even class 1 recommendation.

    Responding to a question at the ACC news conference, Douglas said it is reasonable to question the need for widespread testing of low risk patients. She said the trial investigators will try to identify an extremely low risk subgroup who do not require testing. On the other hand, she said that the use of CTA could help reinforce healthy behaviors and evidence-based interventions.

  2. How the INCONCLUSIVE results of the PROMISE trial can result in upgrading of guideline recommendations for CTA
    escapes me? A class IIa recommendation should be based on an objective assessment of a favorable benefit-risk balance. The results of PROMISE do not allow either an inference of superiority or an inference of non-inferiority!
    What am I missing?
    Am I the only one not looking at the world through rose colored glasses?

  3. Sanjay: Here is my question – the study was powered based on a 9% event rate – and the true rates were around 3% – the NIH shortened the follow-up, which also did not help the number of events. The study could not exclude a 12% benefit of CTA or a 29% harm (they were powered for a 20% reduction based on the higher event rate). They also set a 10% margin for non-inferiority – but they exceeded that too. Am I reading this right – they could not conclude anything about superiority or non-inferiority (that is, CTA is not superior or non-inferior) – and so, after all the investment, what can it tell us? And I was surprised not to read more about that issue. The editorialist did note that the event rates are low and stated “almost half the events were hospitalizations for unstable angina, which is the softest of the end points in the composite.” So regardless of the interpretation, did the NIH truncation of the trial weaken it to the point that it is hard to learn from it? And what about NEJM publishing an underpowered trial?


  4. Harlan,

    You are right. Because the observed event rates were substantially lower than the expected event rates, the study was underpowered. Hence, the results are inconclusive. The study results do not allow either an inference of superiority or an inference of noninferiority. The NIH should have extended the study follow up or expanded the enrollment. Instead, they truncated the study, presumably for budgetary reasons. Imagine the criticism if this action had been undertaken by the pharmaceutical or the device industry. So, at the end of the day, we are left with an uninformative study with no actionable evidence to update the guidelines or guide clinical practice. Our tax dollars deserve to be put to better use!

    Moreover, to endorse CTA as the first line diagnostic tool for evaluation of chest pain on the basis of inconclusive results of the PROMISE trial is a charitable interpretation at best. Quite frankly, the data simply do not allow such a rosy, but misguided, conclusion!


  5. I would like to hear the justification from NHLBI – there is a need to explain why they did not allow the study to be in a position to achieve the power that they had in their proposal. Yes, there would have been a lot of flack for any company that did that. And what about NEJM? They have published a trial that cannot really change the pre-test probability. And what about those who enrolled with the expectation that the trial would provide meaningful information. Would also be useful to hear from representatives of the DSMB.