European Heart Journal - Cardiovascular Imaging (2020) 00, 1–9

doi:10.1093/ehjci/jeaa303

Downloaded from https://academic.oup.com/ehjcimaging/advance-article/doi/10.1093/ehjci/jeaa303/6000249 by University of New England user on 13 December 2020

Relative clinical value of coronary computed
tomography and stress
echocardiography-guided management of
stable chest pain patients: a
propensity-matched analysis
Anastasia Vamvakidou123, Oleksandr Danylenko1,2, Jiwan Pradhan1,
Mihir Kelshiker1, Timothy Jones1, David Whiteside1, Amarjit Sethi3,4, and
Roxy Senior 1,2,3*
1
Department of Cardiology, The Northwick Park Hospital, Watford Rd, Harrow, HA1 3UJ, UK; 2The Royal Brompton Hospital, Sydney Street, Chelsea, SW3 6NP, UK;
3
National Heart and Lung Institute, Imperial College London, Exhibition Rd, South Kensington, London, SW7 2BU, UK; and 4The Ealing Hospital, Uxbridge Road, Southall, UB1
3HW, UK

Received 25 May 2020; editorial decision 22 October 2020; accepted 22 October 2020

Aims The European Society of Cardiology recommends coronary computed tomography (CCT) for the assessment of
low-risk patients with suspected stable angina. We aimed to assess in a real-life setting the relative clinical value of
stress echocardiography (SE)- and CCT-guided management in this population.
...................................................................................................................................................................................................
Methods Patients with stable chest pain and no prior history of coronary artery disease (CAD) who underwent CCT or SE
and results as the initial investigative strategy were propensity-matched (990 patients each group-age: 59 ± 13.2 years, males:
47.9%) to account for baseline differences in cardiovascular risk factors. Inconclusive tests were 6% vs. 3%
(P < 0.005) in CCT vs. SE. Severe (>_70% stenosis) on CCT and inducible ischaemia on SE detected obstructive
CAD by invasive coronary angiography in 63% vs. 57% patients (P = 0.33). Over the follow-up period (median 717,
interquartile range 93–1069 days) more patients underwent invasive coronary angiography (21.5% vs. 7.3%,
P < 0.005), revascularization (7.3% vs. 3.5%, P < 0.005), further functional testing 33.4% vs. 8.7% (P < 0.005), but
more patients were prescribed statins 8.8% vs. 3.8% (P < 0.005) in the CCT vs. the SE arm, respectively. Combined
all-cause mortality and acute myocardial infarction was low—CCT-2.3% and SE-3.3%—with no significant differ-
ence (P = 0.16).
...................................................................................................................................................................................................
Conclusion Initial SE-guided management was similar for the detection of obstructive CAD, demonstrated better resource util-
ization, but was associated with reduced prescription of statins although with no difference in medium-term out-
come compared to CCT in this very low-risk population. However, a randomized study with longer follow-up is
needed to confirm the clinical value of our findings.
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Keywords stress echocardiography • coronary computed tomography • stable chest pain • coronary
angiography • revascularization

* Corresponding author. Tel: þ44 208 869 2547, þ44 207 349 7740; Fax: þ44 207 351 8604, þ44 208 864 0075. E-mail: roxysenior@cardiac-research.org
C The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.
Published on behalf of the European Society of Cardiology. All rights reserved. V
2 A. Vamvakidou et al.
.. chronic kidney disease present at the time of CCT/SE assessment were
Introduction
The recent European Society of Cardiology (ESC) guidelines advo-
cate the use of either coronary computed tomography (CCT) or
functional imaging for the investigation of patients with stable chest
pain, but also suggested that if the likelihood of coronary artery dis-
ease (CAD) and therefore risk is low, CCT should be the preferred
test.1 A previous analysis showed that the estimated death in the
short- and long-term period related to diagnostic tests for the evalu-
ation of suspected angina was lowest with stress echocardiography
(SE).2 Thus, a functional test with equivalent efficacy and with a rela-
tively low diagnostic risk would be ideal in a low-risk population. A
previous study has suggested that over the short-term period of
3 months, CCT when compared with stress imaging (nuclear perfu-
sion imaging, SE, and exercise electrocardiography) was associated
with more subsequent invasive procedures and higher CAD-related
spending.3 However, to our knowledge, no real-life propensity-
matched data has previously been published on the direct compari-
son of CCT with SE over a medium-term follow-up.
We postulated that in real-life scenario in patients with suspected
stable angina and no prior history of CAD, initial testing with SE
would be as efficacious as CCT-guided strategy with less down-
stream testing and interventions. We thus retrospectively investi-
gated this in the real-life scenario in a propensity-matched
population.
Materials and methods
The study is a cohort study comparing the management strategy based
on CCT vs. SE in patients who presented with new-onset suspected sta-
ble angina with no history of CAD. CCT and SE were performed in two
different hospitals but under the same management. The different investi-
gative strategy (CCT or SE as the first line test) was based on their local
expertise and availability. The population was propensity matched to
eliminate as far as possible baseline cardiovascular risk differences.
Study population
A total of 2192 patients underwent CCT and 2082 patients underwent
SE between October 2013 and October 2014. Of these patients only
those with suspected stable angina were selected. Patients with left ven-
tricular ejection fraction <50% detected prior to or within 3 months after
the CCT/SE, were excluded, as their subsequent investigation would
have likely been invasive angiography even in the absence of ischaemia or
any significant disease on CCT. Patients with acute coronary syndrome
and previous CAD were also excluded. Therefore, a total of 1253 in the
CCT and 1402 patients in the SE arms were used for propensity match-
ing. A flow-chart of the study population selection is shown in Figure 1.
Patients were assessed either in a dedicated chest pain (nurse-led) clin-
ic overseen by a consultant cardiologist or in a routine cardiology clinic.
Local protocols and contemporary guidelines were used as reference for
staff performing the assessment.
Cardiovascular risk factors
The typicality of chest pain and angina equivalent symptoms along with
cardiovascular risk factors including age, gender, history of diabetes melli-
tus, systemic hypertension, smoking status, hypercholesterolaemia, family
history of ischaemic heart disease (IHD), peripheral artery disease, and
..
.. recorded.
..
..
.. Coronary computed tomography
.. The scanner used was a Siemens Definition AS 128 slice. Patients initially
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..
.. underwent electrocardiography (ECG)-gated non-enhanced computed
.. tomography (CT) calcium assessment followed in most by CCT angiog-
..
.. raphy. The decision to perform a CCT angiography after coronary cal-
.. cium scoring followed contemporaneous clinical guidelines based on the
.. pre-test probability of CAD and local hospital protocols. Furthermore, if
..
.. severe calcification was found on coronary calcium scoring, patients may
.. not have proceeded to CCT angiography because of its limitation to as-
..
.. sess luminal stenosis.4 For the CCT angiography 95mls contrast
.. (Omnipaque 350 GE Healthcare), metoprolol and sublingual glyceryl-
..
.. nitrate were injected intravenously, and providing heart rate control was
.. adequate, an adaptive prospective-gating acquisition protocol was used.
.. The voltage used for CCT angiographies was 100–120 kV. The coronary
..
.. artery assessment was performed in a Siemens workstation with use of
.. Syngovia analysis software. The radiation exposure dose was recorded as
..
.. dose-length product in millisieverts (mSv) and the radiation effective
.. dose was then calculated with the use of standard methods.5 Mild CAD
.. was defined as epicardial coronary luminal narrowing between 25–49%,
..
.. moderate disease 50–69% and severe >_70%.6
..
..
.. Stress echocardiography
.. Exercise SE was performed with the use of standard or modified Bruce
..
.. treadmill exercise test. In patients who could not exercise a standard
.. dobutamine stress protocol was performed with a starting rate of
..
.. 10 mcg/kg/min for 3 min and 10 mcg/kg/min increments thereafter every
.. 3 min and up to 40 mcg/kg/min. On both occasions (dobutamine SE and
.. exercise SE) ECG and blood pressure monitoring were performed as per
..
.. guidelines and the stress test was terminated when:
..
.. (1) >_85% of target heart rate achieved or
.. (2) limiting shortness of breath, angina, dizziness or syncope or
..
.. (3) fall in systolic blood pressure >_20mmHg or
.. (4) clinically significant arrhythmia like atrial flutter, supraventricular
..
.. tachycardia, ventricular tachycardia.
..
..
.. Contrast administration and interpretation of
.. echocardiographic images
..
.. Contrast (echocardiography enhancing) agents were administered with
.. intermittent intravenous bolus injections (Sonovue-Bracco, Milan, Italy)
..
.. when suboptimal visualization in at least two contiguous segments was
.. present and until optimal left ventricular cavity opacification was
.. achieved.7 Images included apical four-, three-, and two-chamber, para-
..
.. sternal long- and short-axis views. Images were acquired in a quad-screen
.. mode, allowing for comparison between rest and peak stress. The test
..
.. was considered positive for presence of ischaemia if there was reduced
.. left ventricular wall thickening of at least one segment at peak stress.
..
..
.. Study endpoints
..
.. Patients were followed-up at the end of 2 years. The primary endpoint
.. was the number of coronary angiographies and revascularizations per-
.. formed in each group. Secondary endpoints were the number of func-
..
.. tional tests that followed the initial assessment and the new prescription
.. of statins. All-cause mortality, cardiovascular mortality, and myocardial
..
.. infarctions were also assessed. The hospital electronic database and the
.. National Healthcare Care Record Service were used for all outcomes re-
.. view. An intention to treat analysis was used for patients with inconclu-
..
. sive tests.
Relative clinical value of CCT- and SE-guided management of stable chest pain patients
Figure 1 Schematic diagram of study population selection. ACS, acute coronary syndrome; CAD, coronary artery disease; CT, computed tomog-
raphy; HOCM, hypertrophic obstructive cardiomyopathy; LVEF, left ventricular ejection fraction.
..
Cost analysis
A simple cost analysis was performed for the assessment of downstream
resource utilization for each group. The costs of the different tests and
the modes of revascularization were derived from the 2013 to 2014 hos-
pital resource group tariffs, which is the year the tests were performed.
For cardiac stress magnetic resonance imaging and for a more realistic
representation of the cost the code RA07Z (Magnetic Resonance
Imaging Scan, requiring extensive patient repositioning and/or more than
one contrast agent) was selected.8
Reporting protocol
Coronary calcium is largely automated and therefore there is no signifi-
cant interobserver variability reported in the literature.9 CCT angiogra-
phies were jointly reported by one Consultant Cardiologist and one
Consultant Radiologist, and difficult cases were discussed in the Imaging
meeting. Although variability was likely minimized, we do not have specif-
ic data. SE was performed by appropriately trained cardiology fellows and
co-interpreted by a cardiologist (Consultant Cardiologist—R.S.).
Statistical analysis
Categorical and continuous variables were expressed as percentages and
mean values or median values with interquartile range (IQR). Categorical
variables were compared with the use of v2 test.
A propensity score was calculated using a logistic regression model to
correct for differences in patient characteristics, based on widely
accepted predisposing factors for CAD including age, male gender, hyper-
tension, diabetes mellitus, hypercholesterolaemia, smoking, family history
of IHD, peripheral artery disease, and chronic kidney disease in addition
to typicality of chest pain and outpatient or inpatient presentation (11
variables in total). A 1:1 comparison with the nearest neighbour matching
3
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.. using a caliper of 0.2 was performed.10 The propensity score matching
.. excluded unmatched patients of the CCT and SE groups leaving 990
.. patients in each group. Further propensity matching was performed for
..
.. the subgroup of patients who underwent CCT angiography vs. SE (with
.. exclusion of patients who underwent CT calcium scoring only) and 640
..
.. patients for each group were identified.
.. Kaplan–Meier survival curves, log-rank P-values and cox-regression
..
.. analysis were used to evaluate the prognostic impact of each manage-
.. ment strategy. As the number of deaths and myocardial infarctions were
..
.. very low in this population, the combined death, myocardial infarction
.. and late revascularization (>6 months after the initial tests) outcome was
..
.. used to assess the prognostic value of each test. To reduce overfitting
.. due to the low number of events (even when combined events were
.. assessed), the three most significant prognostic variables as per P-values
..
.. in the univariable analysis were selected for inclusion into the multivari-
.. able model.
..
.. For all tests, P < 0.05 was considered statistically significant. Hazard
.. ratios (HRs) with 95% confidence intervals (CIs) were estimated.
..
.. Statistical analysis was performed with SPSS, version 26.0 (SPSS Inc.,
.. Chicago, IL, USA).
..
..
..
..
.. Results
..
.. Demographics
..
.. The demographics of the total and the propensity-matched popula-
..
.. tion are shown in Table 1. The mean age of the propensity-matched
.. population (N = 1980) was 59 ± 13.2 years and 949 (47.9%) of these
..
.. patients were male. The vast majority of patients in the propensity-
.. matched population (83%) presented with chest pain, the remaining
4 A. Vamvakidou et al.

Table 1 Baseline demographic and clinical characteristics of patients undergoing coronary CT vs. stress echocardiog-
raphy in the unmatched and matched populations

Total population (N 5 2648) Propensity-matched cohort (N 5 1980)

........................................................................ ................................................................................

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Coronary CT Stress echo P-value Coronary CT Stress echo P-value
....................................................................................................................................................................................................................
Age 57.9 ± 13.5 60.3 ± 12.7 <0.005 58.8 ± 13.8 59.5 ± 12.5 0.22
Male gender (%) 581 (46.4) 701 (50.2) 0.06 478 (48.3) 471 (47.6) 0.75
Hypertension (%) 502 (40.7) 780 (55.8) <0.005 449 (45.4) 483 (48.8) 0.13
Diabetes mellitus (%) 193 (15.7) 380 (27.2) <0.005 181 (18.3) 203 (20.5) 0.21
Hypercholesterolaemia (%) 468 (38) 722 (51.6) <0.005 428 (43.2) 489 (49.4) 0.01
Smoking (%) 205 (16.7) 304 (21.7) <0.005 189 (19.1) 210 (21.2) 0.24
Family history IHD (%) 279 (22.6) 341 (24.4) 0.28 248 (25.1) 250 (25.3) 0.92
Peripheral artery disease (%) 17 (1.4) 75 (5.4) <0.005 16 (1.6) 17 (1.7) 0.86
Chronic kidney disease (%) 16 (1.3) 57 (4.1) <0.005 15 (1.5) 20 (2) 0.39
Typicality of chest pain score
0 (no chest pain) (%) 265 (21.9) 159 (11.4) <0.005 206 (20.8) 132 (13.3) <0.005
1 (non-anginal) (%) 408 (33.7) 409 (29.2) 304 (30.7) 360 (36.4)
2 (atypical) (%) 445(36.8) 622 (44.5) 390 (39.4) 360 (36.4)
3 (typical) (%) 91 (7.5) 209 (14.9) 90 (9.1) 138 (13.9)
Inpatient status (%) 30 (2.5) 294 (21) <0.005 28 (2.8) 30 (3) 0.79

CT, computed tomography; IHD, ischaemic heart disease.

had angina-equivalent symptoms. The prevalence of typical angina in

.. There were 52 (5.3%) patients with inducible ischaemia at peak
..
the SE arm was higher in both the unmatched and matched .. stress.
population.
..
..
.. Coronary angiography and
Coronary CT and stress ..
.. revascularization following abnormal
echocardiography results ..
.. result of coronary CT and stress
Of the 990 patients who underwent CCT 91 (9.2%) patients had cor- .. echocardiography assessment
onary artery calcium score >_400, 38 (3.8%) had >_1000, and the ..
.. The median follow-up time was 717 (IQR 93–1069) days.
mean coronary artery calcium score was 150.8 ± 520. The mean ef- .. In the patients who underwent CCT, of the 73 patients with mod-
fective radiation dose was 4.5 ± 4.3 mSv. Of the CCT population 458
..
.. erate disease (50–69%), 42 (57.5%) underwent invasive coronary
(46.3%) underwent coronary calcium scoring only and 532 (53.7%) ..
underwent CCT angiography. Sixty-two (6.3%) tests were inconclu-
.. angiography, of which 15 (35.7%) showed obstructive CAD (>_70%
.. stenosis). Of the latter 9 (60%) underwent revascularization. Of the
sive due to uncontrolled heart rate, intolerance to beta-blockers, or ..
poor image quality. There were 27 (2.7%) patients with mild CAD
.. 58 patients with severe disease (>_70% luminal narrowing) 41 (70.1%)
.. underwent invasive coronary angiography, of which 26 (63.4%) had
(25–49% luminal narrowing), 73 (7.4%) patients with at least one epi- ..
cardial coronary artery with 50–69% luminal narrowing, and 58
.. evidence of obstructive CAD. Of the 26 patients with obstructive
.. disease 17 (65.4%) underwent revascularization. Of these 17 patients
(5.9%) with >_70% luminal narrowing (flow-limiting CAD). Therefore, ..
.. that were revascularized, 6 underwent functional imaging and 11
a total of 131 (13.2%) patients had a CCT with at least moderate ..
CAD (>_50%). In total, 502 (50.7%) had normal CCT (0 calcium score .. were performed without prior functional imaging—of these nine had
.. either severe proximal left anterior descending artery or three-vessel
or absence of plaque disease on CCT angiography). ..
Of the 990 patients who had SE 701 (71%) underwent exercise .. disease. Of the nine patients who did not undergo revascularization,
.. seven had functional imaging.
and 285 (28.8%) underwent dobutamine stress. Echocardiography- ..
enhancing (contrast) agent was used in 885 (89.4%) patients. The .. In the SE group, 37 of the 52 (71.2%) patients with inducible ischae-
.. mia underwent invasive coronary angiography of which 21 (57%) had
mean resting HR was 76 ± 13 beats/min and the mean peak HR ..
151 ± 16 beats/min. Of those who underwent treadmill exercise SE .. obstructive CAD. There was no significant difference in the detection
..
the mean exercise time was 7.95 ± 2.7 min and the workload was .. of obstructive disease between CCT with severe disease and SE with
6.2 ± 4.9 metabolic equivalents. Of those who underwent dobut- .. myocardial ischaemia (P = 0.33). Twenty (95.2%) of the 21 patients
..
amine stress the median peak dobutamine dose was 30 (IQR 30–40) .. with obstructive disease underwent revascularization. In all 20
mcg/kg/min. Of the 990 patients, 25 (2.5%) tests were inconclusive .. patients location of ischaemia matched the subtending diseased ves-
..
(due to either intolerance to dobutamine, suboptimal stress, or sub- .. sel (Supplementary data online, Table S1).
optimal quality stress images) which was significantly lower compared
.. Thus, of the patients with severe CAD on CCT and myocardial is-
..
to the proportion of inconclusive tests in the CCT arm (P < 0.005). . chaemia on SE similar proportion of patients (70.1% vs. 71.2%,
Relative clinical value of CCT- and SE-guided management of stable chest pain patients 5

..
.. following CCT and SE, a further 84 patients vs. 30 patients (log-rank
.. P < 0.005) in the CCT vs. SE groups, respectively underwent invasive
..
.. angiography remotely from the initial testing.
..
..

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..
.. Functional imaging post-coronary CT
..
.. and stress echocardiography assessment
.. During the follow-up period, 331 (33.4%) patients in the CCT group
..
.. and 86 (8.7%) in the SE group underwent subsequent functional test-
.. ing (exercise ECG, stress cardiac magnetic resonance imaging, or SE)
..
.. (P < 0.005) (Figure 3A). In the CCT group, 33 of the 73 (45%) patients
.. with moderate disease (50–69%) and 31 of the 58 (53.4%) patients
..
.. with severe disease (>_70% stenosis) underwent further functional
..
.. testing. Of the patients with severe disease who underwent invasive
.. coronary angiography 23 also had functional imaging tests.
..
.. Among patients that underwent revascularization following a non-
.. invasive functional test in the CCT group (N = 47), 25 (53.2%) had is-
..
.. chaemia, 3 (6.4%) had revascularization following acute myocardial
..
.. infarction without ischaemia and there were a total of 11 (23.4%)
.. who did not demonstrate ischaemia. The corresponding figures in
..
Figure 2 Rates of invasive coronary angiography, obstructive .. the SE group (n = 12) were 3 (25%), 4 (33%), and 7 (58.3%), respect-
CAD, and revascularization in patients with myocardial ischaemia .. ively (Supplementary data online, Table S2).
on stress echocardiography vs. flow-limiting CAD on coronary CT.
..
.. A cost analysis based on the cost of baseline CCT and SE tests and
CAD, coronary artery disease; CT, computed tomography. .. of all the subsequent tests (in some cases multiple for the same pa-
..
.. tient) including revascularization is shown in Supplementary data on-
..
.. line, Table S3. The data suggest that despite lower initial cost of CCT,
.. downstream cost was higher in this group compared to SE by
..
P = 0.96, respectively) underwent coronary angiography, of which .. £267 107 (£270/patient).
..
similar proportion of patients between the two groups demonstrated ..
invasive angiographic obstructive CAD (63% vs. 57%, P = 0.26, re- ..
.. Change in statin therapy
spectively), but significantly more patients in the SE group underwent .. In the CCT group, 87 (8.8%) patients had a statin started as a result
revascularization compared to the CCT group (95.2% vs. 65.4%, ..
.. of the CCT, whereas only 38 (3.8%) people were initiated on a statin
P = 0.01) (Figure 2). ..
.. in the SE group (P < 0.005). In the CCT group, the initiation of a statin
.. was associated with a tendency towards significant change in out-
Coronary angiography and ..
.. come (log-rank P = 0.06) as opposed to the SE group where there
revascularization over the entire follow- .. was no significant impact on survival (log-rank P = 0.3).
..
up period ..
Over the entire follow-up period, significantly more patients under- ..
.. Mortality and major cardiovascular
went invasive coronary angiography (213–21.5% vs. 72–7.3%, log- ..
rank P < 0.005) and more patients underwent revascularization (72– .. outcomes
..
7.3% vs. 35–3.5%, log-rank P < 0.005) in the CCT group vs. the SE .. There was no difference in all-cause mortality between the two
group, respectively (Figure 3A) (Table 2).
.. groups (log-rank P = 0.26). Similarly, there was no difference in the
..
In the CCT group, of the total of 213 patients who underwent in- .. combined death and myocardial infarction outcome (log-rank
.. P = 0.16) (Figure 3B, Table 2) or combined cardiovascular death and
vasive angiography, 41 (19%) had severe CAD in the initial CCT angi- ..
ography, 42 (19.7%) had moderate (50–69%) CAD, 40 (18.8%) had .. myocardial infarction (log-rank P = 0.16) (Table 2).
..
raised coronary artery calcium score of >_400, and 6 (2.8%) had in- .. When the combined outcome of death, myocardial infarction, and
conclusive scans. The remaining 84 (39.4%) coronary angiographies .. late revascularization (>6 months) was used, both an abnormal CCT
..
were performed subsequently at a median time of 737 (IQR 114– .. defined as the presence of coronary plaque of any degree and an ab-
1149) days post the initial CCT scan. In these patients, the mean cor-
.. normal SE defined by the presence of ischaemia were significant pre-
..
onary artery calcium score was 14 ± 39, and amongst them 18 .. dictors in the univariable analysis (HR = 70.6, 95% CI = 9.8–509,
..
(21.4%) patients had either minor (<25%) CAD or plaque-free coro- .. P < 0.005 and HR = 4.4, 95% CI = 2.0–9.5, P < 0.005, respectively). In
naries. In the SE group of the 910 with normal scans 28 (3%) patients .. the multivariable analysis, both CCT and SE were independent pre-
..
underwent coronary angiography at a median time of 622 (IQR 13– .. dictors of the combined death, myocardial infarction, and late revas-
995) days and 9 (1%) underwent revascularization. When excluding .. cularization outcome (P < 0.005, HR = 43.7, 95% CI 5.9–322.5 and
..
the patients who underwent invasive coronary angiography initially . P < 0.005, HR 3.6, 95% CI = 1.7–8.3, respectively).
6 A. Vamvakidou et al.

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Figure 3 Further testing and outcome following stress echocardiography vs. coronary CT. (A) Comparison of subsequent functional tests, invasive
coronary angiography, and revascularization. (B) Comparison of outcome (death and composite of myocardial infarction and death). CT, computed
tomography; MI, myocardial infarction.

Table 2 Incidence of invasive coronary angiography, revascularization death, and major cardiac events in the propen-
sity-matched population

Coronary CT Stress echocardiography Hazard ratio P-value

(n 5 990) (n 5 990) (95% CI)
....................................................................................................................................................................................................................
Coronary angiography (%) 213 (21.5) 72 (7.3) 2.86 (2.2–3.7) <0.005
Revascularization (%) 72 (7.3) 35 (3.5) 1.87 (1.24–2.8) <0.005
PCI (%) 52 (5.2) 25 (2.5) 1.87 (1.16–3) 0.01
CABG (%) 20 (2) 10 (1) 1.71 (0.79–3.7) 0.17
Death (%) 18 (1.8) 25 (2.5) 0.71 (0.29–1.29) 0.26
Cardiovascular death (%) 3 (0.3) 4 (0.4) 0.74 (0.16–3.29) 0.69
Myocardial infarction (%) 7 (0.7) 9 (0.9) 0.66 (0.25–1.8) 0.42
Combined death and myocardial 23 (2.3) 33 (3.3) 0.69 (0.4–1.2) 0.16
infarction (%)
Combined cardiovascular death 9 (0.9) 12 (1.2) 0.58 (0.24–1.41) 0.23
and myocardial infarction (%)

CABG, coronary artery bypass grafting; CT, computed tomography; PCI, percutaneous coronary intervention.

Subgroup analysis of CCT angiography ..

.. excluded) vs. SE was evaluated, a total of 1280 patients (640 for each
vs. SE .. group), 64 patients had >_70% luminal narrowing of which 43 (67.2%)
..
When the propensity-matched subgroup of patients who underwent .. underwent invasive coronary angiography and of these 28 (65%) had
CCT angiography (patients with only coronary CT calcium were
.. obstructive CAD and 19 (67.8%) underwent revascularization. Of
Relative clinical value of CCT- and SE-guided management of stable chest pain patients
..
the 28 patients with ischaemia on SE 21 (75%) underwent coronary
angiography of which 11 (52.4%) had obstructive CAD and 11
(100%) were revasularized. There was no significant difference in the
number of coronary angiographies or detection of obstructive CAD
(P = 0.45 and P = 0.22, respectively) between CCT angiography and
SE, but revascularization was significantly less in the CCT angiography
arm following initial testing (P = 0.03).
However, over the entire follow-up period, there was significantly
more invasive coronary angiography (log-rank P < 0.005), revasculari-
zation (log-rank P = 0.03), performed in the CCT angiography group
compared to SE. Furthermore in the CCT angiography group 157
(24.5%) functional tests (exercise ECG, stress cardiac magnetic res-
onance imaging or SE) were performed compared to 53 (8.3%) in the
SE group (P < 0.005).
There was no difference in all-cause mortality (log-rank P = 0.57)
or the combined outcome of death and myocardial infarction (log-
rank P = 0.33).
Discussion
This is the first study comparing the outcome of SE- vs. CCT-guided
management in a propensity-matched population presenting with sus-
pected stable angina without a previous history of CAD over a period
of 2 years in real-world clinical scenario. This study showed that SE
resulted in similar detection of obstructive CAD, but more revasculari-
zation in patients with myocardial ischaemia compared with severe
CAD on CCT. However, over the follow-up period of 2 years in the
CCT-guided management arm, more patients were prescribed statins,
more patients underwent functional tests, invasive coronary angiog-
raphy and revascularization. There was no significant difference in hard
event rates although they were very low in both groups.
With the advent of harmonic imaging and availability of ultrasound-
enhancing (contrast) agents, diagnostic tests during SE have increased
significantly to around 98%, as in the present study, with almost no
contraindication for the performance of SE.11–13 The improved image
quality probably contributed to similar comparable detection of ob-
structive disease to CCT, unlike the PROMISE study where CCT
resulted in better detection of obstructive CAD vs. functional imag-
ing.14 Compared with the SE arm, where almost all patients underwent
revascularization following coronary angiography in the group with
myocardial ischaemia, significantly less revascularization occurred in the
CCT group with severe disease following coronary angiography. This is
likely because despite the discovery of visually obstructive disease on in-
vasive coronary angiography, in some patients, ischaemia testing was
conducted to confirm the functional significance of the disease as
shown in our study, and in some of these patients ischaemia may not
have been demonstrated. In the SE arm, ischaemia data were already
available and the presence of visually obstructed coronary artery on in-
vasive coronary angiography subtended the ischaemic territory. Thus,
the discovery of obstructive disease on coronary angiography gave the
operators mandate to proceed to revascularization.
The increased number of functional tests in the CCT arm was also
because of the uncertainty regarding the functional significance of
moderate-severely graded stenosis where almost 50% of patients
underwent functional testing. Of the invasive coronary angiography
performed in the CCT arm almost half were in patients with
7
.. moderate lesions. The increased rate of revascularization in the CCT
.. arm subsequently was likely because of the higher rates of functional
..
.. tests and invasive coronary angiography in patients with mild-
.. moderate CAD, in some of whom these would have been positive
..
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.. leading to revascularization. The revascularization rates in our study
.. (7.3% in the CCT vs. 3.5% in the SE group) were comparable to what
..
.. was shown in the PROMISE study (6.2% in the CCT vs. 3.2% in the
.. functional testing group), which also reflects similar contemporary
..
.. clinical practice. Based on higher functional tests, invasive coronary
.. angiography and revascularization, the cost in the CCT group was
..
.. higher. It is also worth noting that in both PROMISE and SCOT-
.. HEART (two large randomized controlled trials) the combined out-
..
.. come of death and acute myocardial infarction over a 2-year period
.. was approximately 2.2% (1.1% annually), which was comparable to
..
.. our study findings of 1.5% annually and suggests a low-risk
.. population.14,15
..
.. The increased use of statins in the CCT arm is likely because of the
.. higher detection of CAD. The long-term follow-up study SCOT-
..
.. HEART showed reduction in hard outcomes predominantly driven
.. by myocardial infarction rates in favour of the CCT arm. The study
..
.. also demonstrated higher rates of statin use and the authors postu-
..
.. lated the role of statins in mitigating infarction rates.16 The present
.. study did not show significant difference in the rate of acute myocar-
..
.. dial infarction between the two arms despite higher uptake of statins
.. in the CCT group. However, the follow-up is not long enough for the
..
.. statin effect to manifest and the population is too low risk for statins
.. to make a significant difference in outcome.
..
..
.. Clinical implications
..
.. The recent ESC guidelines on chronic coronary syndromes have
.. downgraded the pre-test probability score of obstructive CAD in
..
.. patients without a history of CAD to reflect the low prevalence and
.. risk of CAD in this population as also demonstrated in the present
..
.. population. The same guidelines advocated CCT angiography or
.. stress imaging as the initial management strategy for patients with sus-
..
.. pected chronic stable angina, but the former was recommended for
.. use preferentially in a low-risk population.1 However, the present
..
.. study performed in the real world in a low-risk population showed
.. that CCT resulted in more functional tests, invasive coronary angiog-
..
.. raphy and revascularization with higher cost implications compared
.. with the SE strategy. Given its relative salutary safety profile, SE may
..
.. be considered to be an equally appropriate test compared with CCT
..
.. for these low-risk patients presenting with suspected stable angina
.. and no previous history of CAD.2 The data suggested that either test
..
.. may be used in centres with appropriately trained staff in the respect-
.. ive modalities. Pros and cons of each test should be considered when
..
.. advocating a test (Supplementary data online, Figure S1).2,13,14,16–28 SE
.. is especially useful in young patients and young females who are rela-
..
.. tively low-risk patients, in whom one would like to avoid techniques
.. involving ionizing radiation. Use of echo-contrast agents significantly
..
.. improves image quality and therefore the diagnostic yield and accur-
.. acy of the test.13 On the other hand, CCT is useful in patients with a
..
.. strong family history of premature CAD where preventative meas-
.. ures may be instituted even if non-obstructive CAD is discovered.
..
.. Further randomized controlled studies with longer-term follow-up,
.. directly comparing the two strategies, are required to confirm the
..
. findings of the present study.
8 A. Vamvakidou et al.

.. coronary artery disease: results from the prospective multicenter ACCURACY

Study limitations ..
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