Meeting News CoveragePerspective

PROMISE: CTA, functional testing associated with similar outcomes in patients with suspected CAD

SAN DIEGO — In symptomatic patients suspected of having CAD requiring noninvasive testing, initial CTA and functional testing had no differences in outcomes at 2 years, according to the results of the PROMISE study.

In an economic analysis from PROMISE, researchers determined that there were no significant differences between the strategies in costs in that patient population over 3 years.

PROMISE is the largest outcome study in CV imaging conducted to date, Pamela S. Douglas, MD, said at a press conference.

Pamela S. Douglas, MD

Pamela S. Douglas

PROMISE: CTA vs. functional testing

Douglas and colleagues randomly assigned 10,003 symptomatic patients (mean age, 60.8 years; 52.7% women; 87.7% with chest pain or dyspnea upon exertion) to initial anatomical testing with coronary CTA or with functional testing, defined as exercise electrocardiography, nuclear stress testing or stress echocardiography. Mean pretest likelihood of obstructive CAD was 53.3%.

They presented their findings at the American College of Cardiology Scientific Sessions. Findings were published simultaneously online in The New England Journal of Medicine.

The composite primary endpoint was death, MI, hospitalization for unstable angina or major procedural difficulties. Secondary endpoints included invasive cardiac catheterization not showing CAD and radiation exposure. Median follow-up was 25 months.

Douglas, who holds the Ursula Geller Professorship for Research in Cardiovascular Diseases at Duke Clinical Research Institute, Duke University School of Medicine, and colleagues found that during the study period, the primary endpoint occurred in 3.3% of patients in the CTA group vs. 3% of those in the functional testing group (adjusted HR = 1.04; 95% CI, 0.83-1.29).

“It is a very significant finding that there was a very low event rate in our patients,” Douglas said.

Compared with functional testing, CTA was associated with fewer catheterizations showing no obstructive CAD (3.4% vs. 4.3%; P = .02), although more people in the CTA group (12.2%) underwent catheterization within 90 days of randomization than those patients in the functional testing group (8.1%), they found.

There were no significant differences between the groups in the secondary endpoints of the primary endpoint plus catheterization without obstructive CAD (HR = 0.91; 95% CI, 0.78-1.06) and death or nonfatal MI (HR = 0.88; 95% CI, 0.67-1.15), Douglas said.

According to the researchers, median cumulative radiation exposure per patient was 10 mSv in the CTA group and 11.3 mSv in the functional testing group, but because 32.6% of patients in the functional testing group had no exposure, the overall exposure was higher in the CTA group (mean, 12 mSv vs. 10.1 mSv; P < .001).

Economic analysis: Similar costs

Daniel B. Mark, MD, MPH

Daniel B. Mark

Daniel B. Mark, MD, MPH, and colleagues conducted an economic substudy of PROMISE to assess economic outcomes and cost effectiveness of the two approaches.

Mark, professor of medicine at Duke Clinical Research Institute and the Duke Heart Center, and colleagues analyzed initial diagnostic test technical fees, hospital-based facility costs and doctor fees.

“A bit of a controversy has broken out in the field,” he said at the press conference. “The pro side says CTA would allow precision care and would allow only the patients who would need revascularization to go to the cath lab.  Everybody else would avoid the need for an invasive test and could be managed noninvasively, so they wouldn’t get extra revascularization, false positives would be reduced and costs would be reduced. The con side says CTA would increase noninvasive and invasive testing, because a lot of the findings on the CTA would be ambiguous, and doctors would want to be certain, so they would do more tests, there would be more radiation exposure and more cost.”

Researchers estimated initial testing costs as $404 per person for CTA, $501 to $514 per person for stress echocardiography, $174 per person for exercise electrocardiography and $946 to $1,132 per person for nuclear stress testing.

However, when the researchers calculated cumulative total costs by intention to treat and mean cost difference, they found that total costs per person for CTA were slightly more than costs for functional testing: $279 at 3 months, $358 at 12 months, $388 at 24 months and $694 at 36 months. The jump from 24 months to 36 months was primarily explained by some outlier patients in the CTA group who required non-CV care, and the other differences were explained by increased revascularization in the CTA group, Mark said.

“Coronary CTA may not be the holy grail of cardiology that we hoped it would be, but its more liberal use following the PROMISE standards  … will definitely improve some aspects of care without causing a major new economic Armageddon in the health care system,” Mark said. – by Erik Swain

References:

Douglas PS, et al. ACC.15 Opening Showcase and the Joint ACC/JACC Late-Breaking Clinical Trials.

Douglas PS, et al. N Engl J Med. 2015;doi:10.1056/NEJMoa1415516.

Mark DB, et al. Joint ACC/JAMA Late-Breaking Clinical Trials. Presented at: American College of Cardiology Scientific Sessions: March 14-16, 2015; San Diego.

Disclosures: The study was funded by the NHLBI. Douglas reports receiving research grants or contracts to her institution from Abiomed, Bristol-Myers Squibb, Edwards Lifesciences, Gilead, HeartFlow, Ikaria/Bellerophon, ResMed, Roche and Stealth Peptides, and receiving royalties from UpToDate/Kluwer. Mark reports receiving grant support from AGA Medical, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Gilead and Oxygen Therapeutics and consulting for CardioDx, Medtronic, Milestone and St. Jude Medical.

SAN DIEGO — In symptomatic patients suspected of having CAD requiring noninvasive testing, initial CTA and functional testing had no differences in outcomes at 2 years, according to the results of the PROMISE study.

In an economic analysis from PROMISE, researchers determined that there were no significant differences between the strategies in costs in that patient population over 3 years.

PROMISE is the largest outcome study in CV imaging conducted to date, Pamela S. Douglas, MD, said at a press conference.

Pamela S. Douglas, MD

Pamela S. Douglas

PROMISE: CTA vs. functional testing

Douglas and colleagues randomly assigned 10,003 symptomatic patients (mean age, 60.8 years; 52.7% women; 87.7% with chest pain or dyspnea upon exertion) to initial anatomical testing with coronary CTA or with functional testing, defined as exercise electrocardiography, nuclear stress testing or stress echocardiography. Mean pretest likelihood of obstructive CAD was 53.3%.

They presented their findings at the American College of Cardiology Scientific Sessions. Findings were published simultaneously online in The New England Journal of Medicine.

The composite primary endpoint was death, MI, hospitalization for unstable angina or major procedural difficulties. Secondary endpoints included invasive cardiac catheterization not showing CAD and radiation exposure. Median follow-up was 25 months.

Douglas, who holds the Ursula Geller Professorship for Research in Cardiovascular Diseases at Duke Clinical Research Institute, Duke University School of Medicine, and colleagues found that during the study period, the primary endpoint occurred in 3.3% of patients in the CTA group vs. 3% of those in the functional testing group (adjusted HR = 1.04; 95% CI, 0.83-1.29).

“It is a very significant finding that there was a very low event rate in our patients,” Douglas said.

Compared with functional testing, CTA was associated with fewer catheterizations showing no obstructive CAD (3.4% vs. 4.3%; P = .02), although more people in the CTA group (12.2%) underwent catheterization within 90 days of randomization than those patients in the functional testing group (8.1%), they found.

There were no significant differences between the groups in the secondary endpoints of the primary endpoint plus catheterization without obstructive CAD (HR = 0.91; 95% CI, 0.78-1.06) and death or nonfatal MI (HR = 0.88; 95% CI, 0.67-1.15), Douglas said.

According to the researchers, median cumulative radiation exposure per patient was 10 mSv in the CTA group and 11.3 mSv in the functional testing group, but because 32.6% of patients in the functional testing group had no exposure, the overall exposure was higher in the CTA group (mean, 12 mSv vs. 10.1 mSv; P < .001).

Economic analysis: Similar costs

Daniel B. Mark, MD, MPH

Daniel B. Mark

Daniel B. Mark, MD, MPH, and colleagues conducted an economic substudy of PROMISE to assess economic outcomes and cost effectiveness of the two approaches.

Mark, professor of medicine at Duke Clinical Research Institute and the Duke Heart Center, and colleagues analyzed initial diagnostic test technical fees, hospital-based facility costs and doctor fees.

“A bit of a controversy has broken out in the field,” he said at the press conference. “The pro side says CTA would allow precision care and would allow only the patients who would need revascularization to go to the cath lab.  Everybody else would avoid the need for an invasive test and could be managed noninvasively, so they wouldn’t get extra revascularization, false positives would be reduced and costs would be reduced. The con side says CTA would increase noninvasive and invasive testing, because a lot of the findings on the CTA would be ambiguous, and doctors would want to be certain, so they would do more tests, there would be more radiation exposure and more cost.”

Researchers estimated initial testing costs as $404 per person for CTA, $501 to $514 per person for stress echocardiography, $174 per person for exercise electrocardiography and $946 to $1,132 per person for nuclear stress testing.

However, when the researchers calculated cumulative total costs by intention to treat and mean cost difference, they found that total costs per person for CTA were slightly more than costs for functional testing: $279 at 3 months, $358 at 12 months, $388 at 24 months and $694 at 36 months. The jump from 24 months to 36 months was primarily explained by some outlier patients in the CTA group who required non-CV care, and the other differences were explained by increased revascularization in the CTA group, Mark said.

“Coronary CTA may not be the holy grail of cardiology that we hoped it would be, but its more liberal use following the PROMISE standards  … will definitely improve some aspects of care without causing a major new economic Armageddon in the health care system,” Mark said. – by Erik Swain

References:

Douglas PS, et al. ACC.15 Opening Showcase and the Joint ACC/JACC Late-Breaking Clinical Trials.

Douglas PS, et al. N Engl J Med. 2015;doi:10.1056/NEJMoa1415516.

Mark DB, et al. Joint ACC/JAMA Late-Breaking Clinical Trials. Presented at: American College of Cardiology Scientific Sessions: March 14-16, 2015; San Diego.

Disclosures: The study was funded by the NHLBI. Douglas reports receiving research grants or contracts to her institution from Abiomed, Bristol-Myers Squibb, Edwards Lifesciences, Gilead, HeartFlow, Ikaria/Bellerophon, ResMed, Roche and Stealth Peptides, and receiving royalties from UpToDate/Kluwer. Mark reports receiving grant support from AGA Medical, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Gilead and Oxygen Therapeutics and consulting for CardioDx, Medtronic, Milestone and St. Jude Medical.

    Perspective
    Robert O. Bonow

    Robert O. Bonow

    The findings will probably result in a slow integration of CTA into practice. I think the results will be quite important in that regard. It’s nice to finally have a randomized trial in imaging looking at outcomes. Of course, it’s not the imaging that drives the outcomes, it’s what you do with the results. If you have more accurate results, you have more of a comfort level in talking with your patients. That may drive you to prescribe medications that are helpful and may encourage patients to take their medications. Although there was no difference in the outcomes, there was a more accurate diagnosis in terms of the catheterization results favoring the patients who went through the CTA-driven strategy. That led to some downstream effects, as more accurate diagnosis leads to more stenting and more procedures, but we didn’t see improvements in the outcomes.

    The guidelines committees will now have more evidence to look at because of PROMISE and SCOT-HEART, and that may lead to stronger support for CTA in the guidelines.

    I don’t think the cost considerations will affect doctors’ decisions. The costs of the tests themselves are not that great; the greater differences come downstream. It all depends on how doctors start behaving. What does a positive CTA mean to them? If it’s a low-risk form of coronary disease, perhaps it will be treated medically. We have data that even with symptomatic coronary disease, in the majority of patients, medical therapy is as good as intervention.  If we have a good CTA making the diagnosis, perhaps we do not need to do the next step, which is going to be more expensive, and can put the patient on statins, which are low-cost.

    • Robert O. Bonow, MD, MS, MACC, FAHA
    • Goldberg Distinguished Professor Vice-Chair, Department of Medicine Director, Center for Cardiovascular Innovation Northwestern University Feinberg School of Medicine Past President, American Heart Association

    Disclosures: Bonow reports no relevant financial disclosures.

    Perspective

    This was an important proof of concept for those of us who have been using cardiac CT and prefer it as the initial testing option in patients with chest pain. It was similar to functional testing in terms of the primary outcomes, which tells us that CTA is a good, viable option for initial testing for coronary disease in patients who have had symptoms.

    Since anatomic assessment with CT was equivalent and not superior to functional assessment, I don’t think there is going to be much of a sea change in terms of how doctors test these patients. There is still a fair amount of technical challenge to performing cardiac CT and performing it well. It is not something that an average cardiologist can perform in their offices, which they can do more easily with stress echocardiography, treadmill or nuclear testing. Had it been shown to be superior, there might be more adoption of it.

    It was interesting that the invasive diagnostic angiography rates after initial testing were a bit higher in the anatomic group. That should serve as a reminder that we need to be cautious and not always jump in and do additional tests if we did choose CTA as the initial test for coronary disease.

    • David E. Winchester, MD, MS, FACC, FACP
    • Assistant professor of medicine University of Florida, Gainesville, Fla.

    Disclosures: Winchester was a site investigator for the PROMISE trial but did not receive compensation.

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