PROMISE Analyses: Coronary CTA May Hold Some Benefits for Patients With Suspected CAD
ORLANDO, FL—Earlier this year, the PROMISE trial failed to show that using coronary CT angiography (CTA) instead of functional testing to evaluate patients with chest pain affects clinical outcomes, but multiple secondary analyses now suggest it may have other benefits, including improvements in prognostic accuracy, safety, and preventive medication use.
The findings presented this week at the American Heart Association 2015 Scientific Sessions suggest that “CTA is a viable alternative to functional testing, and, given newer data, should strongly be considered along with conventional testing as a possible first-line test,” PROMISE principal investigator Pamela Douglas, MD, of Duke Clinical Research Institute (Durham, NC), said during an overview of the trial.
“These real-world results should inform noninvasive test choices in clinical care as well as provide guidance to future studies of diagnostic strategies in suspected heart disease,” she added.
PROMISE randomized 10,003 symptomatic patients with suspected CAD to an initial diagnostic strategy of coronary CTA or functional testing (exercise ECG, nuclear stress testing, or stress echocardiography). Reported in March 2015, the main results showed that rates of the primary composite endpoint (death, MI, hospitalization for unstable angina, or major procedural complication) were similar in the CTA and functional testing groups (3.3% vs 3.0%) through mean follow-up of 25 months.
However, secondary analyses suggest there may be important differences between the strategies.
More Accurate Prediction of Events With CTA
Udo Hoffmann, MD, of Massachusetts General Hospital (Boston, MA), presented data on the prognostic value of CTA vs functional testing in the trial. Test findings were stratified into normal, mildly abnormal, moderately abnormal, and severely abnormal. The proportion of normal results was lower in the CTA compared with the functional testing arm (33.3% vs 78.0%; P = .001).
There was separation in primary endpoint event rates between all 4 strata of severity in the CTA arm, but the mildly abnormal and normal groups in the functional arm did not have statistically different risks. Moreover, the hazard ratios for events with severely and moderately abnormal compared with normal test results were higher with CTA vs functional testing.
The increase in prognostic accuracy with CTA was demonstrated by a larger C-statistic (0.72 vs 0.64; P = .014) and net reclassification index (0.67 vs 0.40).
“All the secondary analyses of the PROMISE trial have to be seen as hypothesis-generating,” Hoffmann said, adding that these results shift the focus to prognostic value and the need for tailoring medical therapy. “What our data suggest is that this will be probably more successful if you use CT as a workup [rather] than functional testing.”
Radiation, Complications, and Incidental Findings
Michael Lu, MD, also of Massachusetts General Hospital, presented a safety analysis comparing patients who underwent CTA and those in whom nuclear stress testing was planned.
For the index test, median radiation dose was lower for CTA than for nuclear stress testing (8.8 vs 12.6 mSv), with a substantially lower proportion of tests resulting in a dose beyond 10 mSv. Cumulative radiation dose through 90 days—a time frame that takes into account all subsequent testing—also was lower with CTA.
There were no major complications associated with either CTA or nuclear stress testing, and the rate of minor complications was less than 1% in both groups.
Incidental findings were much more frequent with CTA. Findings predefined as significant were uncovered in 12% of patients undergoing CTA—including 9% with lung nodules, 1.5% with coronary anomalies, and smaller proportions with pulmonary embolism, pneumonia, and aortic aneurysm or dissection—and seen in 0.4% of those undergoing nuclear stress testing.
“Given these findings of a lower radiation dose and an ability to detect potentially clinically meaningful pathology makes CTA an attractive first-choice test for patients with suspected CAD,” Lu concluded.
Modest Increases in Preventive Medication Use
Joseph Ladapo, MD, PhD, of NYU Langone Medical Center (New York, NY), presented information on changes in medical therapy and lifestyle practices in the 60 days after initial diagnostic testing, which he said may represent a teachable moment for patients.
At baseline, use of aspirin, statins, beta-blockers, and ACE inhibitors/angiotensin receptor blockers (ARBs); tobacco use; performance of regular exercise; and the proportion of patients with a body mass index ≥ 25 kg/m2 were similar in both arms of the trial, but differences emerged over the next 2 months.
The percentage of patients newly initiating therapy was higher with CTA vs functional testing for aspirin (11.8% vs 7.8%), statins (12.7% vs 6.2%), and beta-blockers (8.1% vs 5.3%; P < .0001 for all), but not for ACE inhibitors/ARBs. Thus, the overall prevalence of use at 60 days was greater in the CTA arm for the first 3 medication classes.
About one-quarter of patients started exercising regularly after the initial diagnostic test, but there were no differences between the CTA and functional testing groups for that outcome or for smoking cessation or weight loss.
After adjustment for clinical characteristics, test results, and early revascularization, the use of aspirin, statins, and beta-blockers remained higher in the CTA arm. Patients in the CTA group also were more likely to consume a heart-healthy diet (OR 1.15; 95% CI 1.05-1.25) and have a normal body weight (OR 1.27; 95% CI 1.01-1.59).
The analysis was limited by the inability to tease out how physician and patient preferences may have influenced use of preventive medications and lifestyle practices and by the fact that patients self-reported these outcomes without confirmation of adherence, Ladapo said.
Nevertheless, he concluded, “these findings may represent a
long-term benefit of a CTA testing strategy.”
1. Douglas PS. Outcomes of anatomical versus functional testing for coronary artery disease. Presented at: American Heart Association Scientific Sessions; November 8, 2015; Orlando, FL.
2. Lu MT, Douglas PS, Udelson JE, et al. Safety of anatomic versus functional diagnostic testing: insights from the PROMISE trial. Presented at: American Heart Association Scientific Sessions; November 9, 2015; Orlando, FL.
3. Hoffmann U, Ferencik M, Udelson JE, et al. Prognostic value of anatomic versus functional diagnostic testing in symptomatic patients with suspected CAD: the PROMISE trial. Presented at: American Heart Association Scientific Sessions; November 9, 2015; Orlando, FL.
4. Ladapo JA, Hoffmann U, Lee KL, et al. Changes in medical therapy and lifestyle after anatomical versus functional testing for coronary artery disease: the PROMISE trial. Presented at: American Heart Association Scientific Sessions; November 9, 2015; Orlando, FL.
- PROMISE was funded by the National Heart, Lung, and Blood Institute.
- Douglas reports a relevant relationship with HeartFlow.
- Hoffmann reports receiving research grants from the American College of Radiology Imaging Network, HeartFlow, and Siemens Healthcare.
- Ladapo reports serving as a consultant to CardioDx.
- Lu reports no relevant conflicts of interest.