Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT00825435 |
| Other study ID # |
032007-067 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 3
|
| First received |
|
| Last updated |
|
| Start date |
October 2008 |
| Est. completion date |
September 2012 |
Study information
| Verified date |
September 2019 |
| Source |
University of Texas Southwestern Medical Center |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
This study will evaluate the impact of adding coronary computed tomographic angiography (CTA)
on health care costs for diagnosing patients with acute chest pain.
Description:
Background and Significance
Standard-of-care risk-stratification algorithm (SOC):
In the past 20 years since Goldman et al4 described a clinical algorithm to predict MI in ED
patients, the clinical ability to decrease the false-negative rate for myocardial events has
not improved. Hence, the emergency physician (EP) is compelled to admit to the hospital the
majority of patients who present with acute chest pain for further observation and
investigation due to inconclusive evidence of ACS or MI during the index ED visit;
false-negatives are still sent home with CAD; and false-positives are admitted without CAD;
accounting for a significant consumption of resources every year in the US1.
The current state of the art for EPs includes clinical data, electrocardiograms (ECGs) and
cardiac biomarkers5 (Fig. 1). The limitations of using the Goldman prediction rule and the
ECG is that they are insensitive indicators of myocardial injury in patients with MI4-9. The
sensitivity and specificity of cardiac biomarkers is proportional to the time from onset of
chest pain. Cardiac troponin begins to rise within 3-4 hours after the onset of myocardial
injury and may remain increased for up to 4-7 days for cTnI and 10-14 days for cTnT10. There
is enthusiasm for myoglobin as an early marker; however, myoglobin is non-specific11-16 In ED
based trials; cardiac biomarkers have performed well but have not changed the cost and
admission rate (false-positives). In 1999, McCord et al9 published a single center
prospective cohort study that examined point-of-care cardiac biomarkers during the first 90
minutes and if they could help to exclude AMI in the ED chest pain patient. The post-hoc
analysis and resultant negative predictive value (NPV) was 98 to 99% at time 0 minutes, 90
minutes, and 3-hours with various combinations of the three biomarkers including Myoglobin,
Troponin I and CK-MB. These results demonstrated a consistency of negative predictive values
with both combinations of CK-MB with myoglobin equal to Troponin with myoglobin. In 2004,
Fesmire, et al17 reported in another prospective ED cohort study that a 2-hour delta CK-MB
level outperforms myoglobin level in the early identification and exclusion of acute MI and
can effectively risk-stratify patients for 30-day adverse outcomes. In both of these ED based
trials, despite the impressive post-hoc NPV in the McCord et al trial, the cost and admission
rate (false-positives) remains the same since the rule-out MI process requires admission and
24 hours of serial cardiac enzyme testing.
Patients presenting to the ED with acute chest pain undergo the SOC risk-stratification
algorithm to determine the etiology of the complaint (Figure 1). The SOC risk-stratification
initially includes the clinical assessment and an ECG. If the ECG reveals an ST elevation MI
(STEMI) the patient is treated immediately in the cardiac catheterization laboratory. If the
ECG is normal or indeterminate, and there are clinical risk factors, the patient will undergo
cardiac biomarker testing. If the cardiac biomarkers are negative, the patient will then be
admitted to the hospital for further testing. If the cardiac biomarkers are positive, the
patient will be admitted to the cardiac care unit (CCU) for further testing. If the clinical
risk factors are absent and the ECG is normal, the patient may be discharged without further
testing4-8, however this is practiced in a small percentage (11%) of patients9. This practice
risk-stratification algorithm continues to be the SOC. However, the combination of the
Goldman predictor risk algorithm (ECG and symptoms) with a Troponin I (cTnI) < 0.3 was not
able to identify a group of chest pain patients at <1% risk for the composite outcome of
death, AMI or revascularization18. Further demonstrating the need for integration of
additional testing that will decrease the false-positive and false-negative rates.
Adding nuclear perfusion cardiac testing to the SOC risk-stratification in the ED:
Investigators have studied adding exercise stress testing and echocardiograms in the ED in
the SOC risk-stratification of acute chest pain. Both the exercise stress test and the
echocardiogram can be enhanced with the addition of nuclear perfusion that can define recent
reduction in arterial flow to specific segments of the myocardium. Due to the known weakness
of exercise testing 19 and the cost of adding nuclear perfusion enhancement to both the
exercise stress test and the echocardiogram, neither study findings have informed the
standard-of-care risk-stratification algorithm20-22. Furthermore, no apriori clinical
research had performed a cost-analysis to confirm the obvious excessive expense of adding
nuclear study in chest pain patients. However, stress testing is considered a worthy test to
include in the risk-stratification algorithm because it is capable of detecting flow limiting
stenosis, though does not establish the presence or absence of coronary artery disease.
Adding non-invasive cardiac imaging: Coronary CT angiography (CTA) to the SOC (CTA + SOC)
risk-stratification in the ED:
Appropriate decision-making in the low to intermediate-risk subgroup of patients presenting
with acute chest pain requires new tools. We postulate that perhaps the incorporation of
coronary CTA can, by providing an anatomical window that defines the amount of
atherosclerotic burden within the coronary tree, advance the risk-stratification algorithm in
low to intermediate-risk acute chest pain in a cost-effective manner. In recent years, there
has been much interest in noninvasive imaging techniques that allow direct visualization and
assessment of the coronary arteries (Image A). The coronary tree is challenging to image due
to the continuous motion of the coronary arteries. This motion necessitates both high spatial
and temporal resolution. Recent advances in computed tomography (CT) techniques have made
imaging of the coronary arteries possible. The introduction of electron-beam CT (EBCT) in
1984 first allowed for ECG-synchronized imaging of the heart. In 1998, the first multiple
detector spiral CT (MDCT) system with 4 detector rows was introduced, allowing for greater
volume of coverage with each rotation of the CT gantry than EBCT. 23 Since that time, gantry
rotation times have decreased, resulting in improved temporal resolution. An increase in
number of detectors has allowed for sub-millimeter spatial resolution. At this time, 64 slice
MDCT (Image A) is considered the "state of the art" technology for performance of coronary
CTA, although the next generation of scanners, including dual source and 256 slice MDCT are
currently under evaluation. Several small studies in the literature have shown the utility of
coronary CTA in the safe and rapid triage of low to intermediate-risk acute chest pain
patients presenting to the ED24-29. One of the clinical advantages of the coronary CTA is
that, unlike stress testing that can detect flow limiting stenosis but not CAD; it can detect
flow limiting stenosis in addition to the presence or absence of coronary artery disease. The
disadvantage of coronary CTA is the exposure to radiation.
Multiple small trials comparing coronary CTA with invasive coronary angiography have
demonstrated sensitivities ranging from 86-99% and specificities ranging from 93-97% for the
detection of hemodynamically significant CAD. The negative predictive value (NPV) of coronary
CTA in these studies was uniformly high, ranging from 95-99%, while rates of non-evaluable
segments were low, ranging from 0-12%23, 30-34. Results of the multicenter, international
CORE-64 trial were discussed at the 2007 American Heart Association Scientific Sessions
evaluating the diagnostic performance of coronary CTA as compared with interventional
coronary angiography in 291 patients with suspected or known CAD and Agatston calcium score
<600. On a per patient basis, the sensitivity and specificity of coronary CTA for detection
of significant CAD were 85% and 90%, while positive and NPV were 91% and 83%35. Moreover, in
2007, Meijboom et al36 reported on the utility of the coronary CTA in symptomatic patients
with low, intermediate, or high estimated pretest probability of having significant CAD. Of
the 254 patients enrolled in the study, the authors determined that all of the patients in
both the low and intermediate-risk groups that were found to not have disease by coronary CTA
were later determined to not have disease by invasive coronary angiography. Patients
presenting to the ED with acute chest pain could potentially undergo more rapid triage with
coronary CTA, speeding diagnosis, lowering hospital and further cost of testing.
Additional reports on cost-analyses in populations when adding coronary CTA to the SOC
risk-stratification algorithm (CTA + SOC):
In a study by Goldstein et al published in 2007 in Journal of the American College of
Cardiology, the authors reported that ED cost during the index visit was significantly lower
in the group that received the coronary CTA versus the group that did not receive the
coronary CTA. However, this cost difference was primarily due to a decrease in length of stay
in the ED rather than the cost associated with other testing, specifically nuclear imaging.
This cost analysis was limited to the index ED visits alone; since the study was powered for
outcomes, not cost. No additional cost data was gathered, although outcome follow-up was
6-months.
Preliminary cost-outcome data presented at the Chicago 2008 American College of Cardiology
meeting reported that; when including coronary CT calcium scores in the protocol to screen
495 asymptomatic firefighters, researchers were able to effectively triage subjects into
follow-up coronary CTA or send them back to work without further workup, thus, decreasing
cost. In another report presented, researchers concluded that cost was decreased in an
out-patient cardiology clinic by incorporating coronary CTA in the risk-stratification of
cardiac patients leading to reduced need for myocardial perfusion imaging and exercise
treadmill testing over a 6-month period. Moreover, doctors were able to identify more
coronary artery disease and provide more aggressive lipid management.
These data illustrate how cost and outcome studies are at the forefront of the research that
is measuring and defining the role of coronary CTA. The coronary CTA is so innovative in the
domain of acute chest pain, there is a paucity of published work that looks at the cost;
instead, the majority of the literature examines outcomes and is produced primarily by
cardiology.
Healthcare cost implications when adding coronary CTA to the SOC (CTA + SOC); and the
coronary CTA demonstrates normal coronary arteries:
The cost implications of potentially discharging patients from the ED that are found to be
free of CAD without further testing are impressive. In May of 2008, data in abstract form
were presented in Academic EM where authors reported good NPV in 568 prospective patients who
received coronary CTA in the ED at 30-days. These reports lacked a description of design,
methodology, and a stated power calculation of an a priori hypothesis. Thus, the need for
more definitive apriori cost and outcome clinical research in the application of coronary CTA
in acute chest pain is warranted. The effect of this work will define and change the clinical
practice landscape when applying this innovation to the cardiac risk-stratification model,
particularly in acutely presenting chest pain. Embracing the incorporation of coronary CTA in
acute chest pain is an innovation that will require well performed clinical trials to define
the patients who will benefit most; whether it should be applied to asymptomatic patients,
low, intermediate, and/or high-risk acute chest pain patients remains the question.
