Prospective Multicenter Imaging Study for Evaluation of Chest Pain - PROMISE

Contribution To Literature:

The PROMISE trial showed that coronary CTA, while not superior, is an alternative to stress testing among low- to intermediate-risk patients presenting with chest pain.


The goal of the trial was to evaluate anatomical testing compared with functional testing among low- to intermediate-risk patients with chest pain suspicious for coronary artery disease.

Study Design

  • Parallel
  • Randomized
  • Stratified

Low- to intermediate-risk patients with chest pain were randomized to evaluation with an anatomical strategy (n = 4,996) versus a functional strategy (n = 5,007). Patients randomized to an anatomical strategy underwent a 64-slice coronary computed tomography angiography (CTA), while patients randomized to a functional strategy underwent exercise electrocardiography (ECG), exercise imaging, or pharmacologic imaging.

Patient population:

  • Total number of enrollees: 10,003
  • Duration of follow-up: median 25 months
  • Mean patient age: 61 years
  • Percentage female: 53%
  • Percentage diabetics: 21%
  • Among either group who underwent a functional test, 68% underwent nuclear stress testing, 22% underwent stress echocardiography, and 10% underwent exercise ECG

Inclusion criteria:

  • Patients with chest pain suspicious for coronary disease
  • No history of coronary disease or prior evaluation
  • Age ≥55 years for men or ≥65 years for women without risk factors
  • Age 45-54 years for men or 50-64 years for women with at least one cardiac risk factor

Exclusion criteria:

  • Unstable hemodynamics or arrhythmias
  • Urgent evaluation for rule-out acute coronary syndrome
  • Congenital, valvular, or cardiomyopathic heart disease

Principal Findings:

The primary outcome, all-cause mortality, myocardial infarction, unstable angina hospitalization, or major complication from a cardiovascular procedure occurred in 3.3% of the anatomical testing group versus 3.0% of the functional testing group (p = 0.75).

Among women, a positive CTA vs. a negative CTA was more strongly associated with subsequent clinical events (hazard ratio [HR] 5.9, 95% confidence interval [CI] 3.3-10.4) than a positive stress test vs. a negative stress test (HR 2.3, 95% CI 1.2-4.3). Among men, the association between a positive CTA vs. a negative CTA was HR 2.8, 95% CI 1.8-4.5, and a positive stress test vs. a negative stress test was HR 4.4, 95% CI 2.8-7.1.

In the CTA group, 54% of events occurred among subjects with nonobstructive coronary artery disease. When test results were stratified as mildly, moderately, or severely abnormal, events increased proportionated in the CTA group, but not the functional testing group.

Coronary stenosis ≥70% or ≥50% left main stenosis occurred in 9.5% of those with high-sensitivity troponin I (hsTnI) ≤1.0 ng/L, 10.5% of those with hsTnI 1.1-1.5 ng/L, 13.5% of those with hsTnI 1.6-2.4 ng/L, and 16.2% of those with hsTnI ≥2.5 ng/L (p = 0.009).

Secondary outcomes:

  • Catheterization within 90 days: 12.2% vs. 8.1%, respectively, for anatomical vs. functional testing
  • Invasive catheterization showing no obstructive coronary disease: 3.4% vs. 4.3% (p = 0.02), respectively
  • Cumulative radiation exposure: 12.0 mSv vs. 10.1 mSv (p < 0.001), respectively

Economic comparison: Coronary CTA was associated with a small, but nonsignificant increase in costs over a median of 2 years versus functional testing.

Quality of life: Quality-of-life measures improved over time in both groups; however, there was no difference between anatomical testing versus functional testing over 2 years.

In the CTA group, 84% of events occurred in those with a coronary artery calcium score of >0, while in the functional testing group, 43% of events occurred in those with any abnormality.

Comparison of Coronary Artery Disease Reporting and Data System (CAD-RADS) vs. coronary artery calcium score for prediction of the primary outcome:

  • Prognostic value of CAD-RADS, C-statistic = 0.747
  • Prognostic value of coronary artery calcium score, C-statistic = 0.657
  • Prognostic value of atherosclerotic cardiovascular disease (ASCVD) risk calculation, C-statistic = 0.629


Among low- to intermediate-risk patients with chest pain, anatomical testing with coronary CTA was not superior to functional testing. However, coronary CTA resulted in similar adverse events compared with functional testing and thus represents an acceptable mode of evaluation of these patients. The prognostic information for a CTA appears to vary according to gender. Higher concentrations of hsTnI were associated with increased prevalence of obstructive coronary disease. CAD-RADS had better prognostic value at predicting major adverse cardiovascular events compared with coronary artery calcium scoring or ASCVD risk calculation.

Anatomical testing was associated with an increased frequency of cardiac catheterization; however, it was associated with a lower frequency of invasive catheterization showing nonobstructive coronary disease. Anatomical testing was also associated with increased radiation exposure and a nonsignificant increase in total costs. Since CTA is able to detect nonobstructive coronary artery disease, the discriminatory ability of CTA in predicting events is better than functional testing. In other words, coronary artery calcium was more sensitive for predicting adverse events, while functional testing was more specific.


Bittner DO, Mayrhofer T, Budoff M, et al., on behalf of the PROMISE Investigators. Prognostic Value of Coronary CTA in Stable Chest Pain: CAD-RADS, CAC, and Cardiovascular Events in PROMISE. JACC Cardiovasc Imaging 2019;Nov 13:[Epub ahead of print].

Januzzi JL Jr, Suchindran S, Coles A, et al., on behalf of the PROMISE Investigators. High-Sensitivity Troponin I and Coronary Computed Tomography in Symptomatic Outpatients With Suspected CAD: Insights From the PROMISE Trial. JACC Cardiovasc Imaging 2019;12:1047-55.

Budoff MJ, Mayrhofer T, Ferencik M, et al. StudyPrognostic Value of Coronary Artery Calcium in the PROMISE Study (Prospective Multicenter Imaging Study for Evaluation of Chest Pain). Circulation 2017;136:1993-2005.

Editorial: Newby DE. Computed Tomography or Functional Stress Testing for the Prediction of Risk: Can I Have My Cake and Eat It? Circulation 2017;136:2006-8.

Presented by Dr. Marcos Ferencik at the European Society of Cardiology Congress, Barcelona, Spain, August 28, 2017.

Hoffmann U, Ferencik M, Udelson JE, et al. Prognostic value of noninvasive cardiovascular testing in patients with stable chest pain: insights from the PROMISE trial. Circulation 2017;Apr 7:[Epub ahead of print].

Mark DB, Anstrom KJ, Sheng S, et al. Quality of Life Outcomes With Anatomic Versus Functional Diagnostic Testing Strategies in Symptomatic Patients With Suspected Coronary Artery Disease: Results From the PROMISE Randomized Trial. Circulation 2016;Apr 27:[Epub ahead of print].

Pagidipati NJ, Hemal K, Coles A, et al. Sex Differences in Functional Stress Test Versus CT Angiography in Symptomatic Patients With Suspected CAD: Insights From PROMISE. J Am Coll Cardiol 2016;Apr 4:[Epub ahead of print].

Presented by Dr. Neha J. Pagidipati at the American College of Cardiology Scientific Session, Chicago, IL, April 4, 2016.

Douglas PS, Hoffmann U, Patel MR, et al., on behalf of the PROMISE Investigators. Outcomes of Anatomical Versus Functional Testing for Coronary Artery Disease. N Engl J Med 2015;Mar 14:[Epub ahead of print].

Editorial Comment: Kramer CM. Cardiovascular Imaging and Outcomes -- PROMISEs to Keep. N Engl J Med 2015;Mar 14:[Epub ahead of print].

Presented by Dr. Pamela S. Douglas at ACC.15, San Diego, CA, March 14, 2015.

Economic comparison presented by Dr. Daniel B. Mark at ACC.15, San Diego, CA, March 15, 2015.

Clinical Topics: Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Stable Ischemic Heart Disease, Atherosclerotic Disease (CAD/PAD), Interventions and Coronary Artery Disease, Interventions and Imaging, Angiography, Computed Tomography, Nuclear Imaging, Chronic Angina

Keywords: ACC Annual Scientific Session, Anaphylaxis, Angina, Unstable, Angiography, Cardiac Catheterization, Chest Pain, Constriction, Pathologic, Coronary Artery Disease, Coronary Stenosis, Electrocardiography, Hospitalization, Myocardial Infarction, National Heart, Lung, and Blood Institute (U.S.), Prospective Studies, Renal Insufficiency, Stroke, Diagnostic Imaging, Angina, Stable, Tomography, Emission-Computed, Troponin I, ESC2017, ESC Congress

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