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New England Journal of Medicine 18-05971

ORIGINAL ARTICLE

Coronary CT Angiography

and the Future Risk of Myocardial Infarction

Newby DE,1 Adamson PD,1 Berry C,2 Boon NA,1 Dweck MR,1 Flather M,3 Forbes J,4

Hunter A,1 Lewis S,1 MacLean S,5 Mills NL,1 Norrie J,1 Roditi G,2 Shah ASV,1 Timmis

AD,6 van Beek EJR,1 Williams MC1 on behalf of The SCOT-HEART Investigators

1University of Edinburgh, 2University of Glasgow, 3University of East Anglia, 4University of Limerick, 5NHS Fife, and 6Queen Mary University London.

Corresponding Author:

Name: Professor David E. Newby, DMBritish Heart Foundation John Wheatley Chair of Cardiology

Address: British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Room SU314,Chancellor’s Building, 49 Little France Crescent, Edinburgh, Scotland, EH16 4SA

Email: [email protected]: +44 131 242 6515Fax: +44 131 242 6379

SponsorThe University of Edinburgh and NHS Lothian Health Board were co-sponsors.

Trial RegistrationClinicalTrials.gov Identifier: NCT01149590

KeywordsCoronary heart disease, computed tomography, angina pectoris.

Word Count2,666 Words

Abstract Word Count249 Words

1


Abstract

Background. Although coronary computed tomography (CT) angiography improves

diagnostic certainty in patients with stable chest pain, its impact on 5-year clinical

outcomes is unknown.

Methods. In an open-label parallel-group multicenter trial, we randomized 4,146

patients referred with stable chest pain to standard care plus coronary CT angiography

(n=2,073) or standard care alone (n=2,073). Investigations, treatments and outcomes

were assessed over 3-7 years of follow-up. The principal end point was coronary heart

disease death or non-fatal myocardial infarction at 5 years.

Results. Over a median of 4.8 years, we had 20,254 patient-years of follow-up. Despite

apparent early increases, overall rates of invasive angiography (491 versus 502; hazard

ratio [HR] 1.00; 95% confidence interval [CI], 0.88 to 1.13) and coronary

revascularization (279 versus 267; HR 1.07; 95% CI, 0.91 to 1.27) were similar at 5

years although more preventative (odds ratio [OR] 1.40; 95% CI, 1.19 to 1.65) and anti-

anginal (OR 1.27; 95% CI, 1.05 to 1.54) therapies were initiated in those undergoing

coronary CT angiography. The 5-year principal end point was reduced in patients who

underwent coronary CT angiography (48 [2.3%] versus 81 [3.9%]; HR 0.59; 95% CU,

0.41 to 0.84; p=0.004). There were no differences in the rates of cardiovascular, non-

cardiovascular or all-cause deaths.

Conclusions. In this trial, the use of coronary CT angiography in patients with stable

chest pain resulted in a significant reduction in the rate of coronary heart disease death

or non-fatal myocardial infarction at five years without increasing rates of coronary

angiography or coronary revascularization.

Trial Registration. ClinicalTrials.gov: NCT01149590

2


Introduction

Patients with stable chest pain suggestive of coronary heart disease can be evaluated

with a variety of non-invasive stress tests that incorporate electrocardiography,

radionuclide scintigraphy, echocardiography, or magnetic resonance imaging.1-6 Over

the last 50 years or more, these techniques have been demonstrated to be useful in

assisting with the diagnosis of coronary heart disease, as well as in providing important

prognostic information. As such, they are the focus of current international guidelines

for the investigation of patients with stable chest pain.4-6

Coronary computed tomography (CT) angiography is increasingly being used to assess

patients with stable chest pain since it has high sensitivity and specificity for the

detection of coronary heart disease.7,8 In the Scottish Computed Tomography of the

Heart (SCOT-HEART) trial,9 we have previously demonstrated that in patients referred

to the cardiology clinic with stable chest pain, coronary CT angiography clarified the

diagnosis and altered subsequent investigations and treatments.9 Subsequent post-hoc

analyses identified that apparent improvements in clinical outcome coincided with

implementation of the coronary CT angiography findings.10 The Prospective Multicenter

Imaging Study for Evaluation of chest pain (PROMISE) trial also investigated patients

with symptoms suggestive of coronary heart disease who required further non-invasive

testing.11 In a head-to-head comparison, functional tests were compared to coronary CT

angiography, with no difference in clinical outcomes.

Both the SCOT-HEART and PROMISE trials followed patients for a relatively short

time period (20-22 months) and the longer-term effects on coronary heart disease events

3


are unknown. We now report the pre-specified 5-year clinical outcomes of the SCOT-

HEART trial13 in order to determine the impact of coronary CT angiography on longer-

term investigations, treatments and clinical events.

4


Methods

Trial Design and Oversight

This was an open-label parallel-group randomized controlled trial in 12 centers across

Scotland. The study has been described previously9,10,13 and was conducted with the

approval of the South East Scotland Research Ethics Committee. The protocol, which is

available with the full text of this article at NEJM.org, was designed by the grant

applicants (see the Supplementary Appendix) with input from the trial steering

committee.

The Chief Scientist Office of the Scottish Government funded the trial with

supplementary support from the British Heart Foundation, Edinburgh and Lothian’s

Health Foundation Trust and the Heart Diseases Research Fund. The funders played no

role in the design, conduct, data collection, analysis or reporting of the trial. The

steering committee vouches for the accuracy and completeness of the data and the

analyses, as well as for the fidelity of the trial to the protocol.

Patient Population and Randomization

Patients aged 18-75 years of age with stable chest pain who were referred by a primary

care physician to a cardiology out-patient clinic were eligible for inclusion.9,10,13

Exclusion criteria are provided in the Supplementary Appendix. All participants

provided written informed consent.

5


All patients underwent routine clinic evaluation including, if deemed appropriate,

symptom-limited exercise electrocardiography. Symptoms, diagnosis, further

investigations (stress imaging or invasive coronary angiography) and treatment strategy

were documented at the end of the clinic, and before recruitment or randomization.

Patients were then randomized (1:1) to standard care plus coronary CT angiography or

standard care alone using web-based randomization to ensure allocation concealment.

Randomization incorporated minimization to ensure matching for age, sex, body-mass

index, diabetes mellitus, prior history of coronary heart disease, and atrial fibrillation.

Subsequent Investigations and Treatments

Patient management was at the discretion of the attending clinician in the light of all

available information. Physicians caring for patients in the coronary CT angiography

group were prompted to consider the coronary CT angiogram in their management

decisions, while physicians caring for patients in the standard-care group were prompted

to consider a prespecified cardiovascular risk score (the ASSIGN score;14 see

Supplementary Appendix) in their management decisions. Specifically, in the presence

of non-obstructive (10-70% cross-sectional luminal stenosis) or obstructive coronary

artery disease on the coronary CT angiogram, or an ASSIGN score ≥20, the attending

clinician and primary care physician were prompted to prescribe preventative therapies

(aspirin and a statin) by the trial co-ordinating center.13 The ASSIGN score ranges from

1 to 99, with higher scores denoting higher cardiovascular disease risk.

Clinical Follow-Up

There were no trial-specific study visits, and all follow-up was obtained from routinely

collected data of the Information and Statistics Division, and the electronic Data

6


Research and Innovation Service of the National Health Service (NHS) Scotland

(Supplementary Appendix) as described previously.9,10 The in-patient and day-case

national dataset collects episode-level data across all hospitals in Scotland. This

includes discharge diagnostic codes using the International Classification of Disease,

10th Revision, system and procedural codes using the Office of Population Censuses and

Surveys’ Classification of Interventions and Procedures as described previously.9,10,15-17

Process-of-Care Outcomes

Rates of invasive angiography and coronary revascularization (percutaneous coronary

intervention and coronary-artery bypass graft surgery) were obtained from in-patient

and day-case episodes, and cross-checked using review of individual coronary

angiograms within the national Picture Archiving and Communications Systems.9,10

Documentation of participant medications was obtained from the Scottish national

community drug-prescribing database of the Information and Statistics Division in NHS

Scotland (Supplementary Appendix).10

Clinical Outcomes

Clinical outcomes assessed included deaths (all-cause, cardiovascular, coronary heart

disease, and non-cardiovascular), myocardial infarction and stroke. There was no formal

event adjudication, and outcomes were primarily based on diagnostic codes. However,

in cases of uncertainty, categorization of events and cause of death were classified by

two of the authors, who were blinded to trial allocation.9

7


Data Analysis

The original primary end point of the trial was the proportion of

patients diagnosed with angina pectoris secondary to coronary heart

disease at 6 weeks.9 However, acknowledging the potential long-term clinical

consequences of a change in diagnosis, our pre-specified principal long-term end point

was the proportion of patients with coronary heart disease death or non-fatal myocardial

infarction at 5 years.13 Based on an estimated 5-year event rate of 13.1%, the study had

80% power to detect an absolute decrease of 2.8% with a two-sided p<0.05.13

All analyses were by intention-to-treat. Missing data were removed from analyses,

except for survival end points, where they were censored at the time they were lost from

the study. Clinical outcomes were analysed using Cox regression, adjusted for center

and minimization variables, and cumulative event curves were constructed. We also

performed a post hoc 12-month landmark analysis, reasoning that any alterations in

invasive coronary angiography and coronary revascularization driven by the results of

coronary CT angiography should have been completed by this time point.

Data are presented as mean±standard deviation, median [interquartile range] and hazard

or odds ratio [95% confidence interval] as appropriate. Because there was no

correction for multiplicity when testing secondary or other outcomes,

results are reported as point estimates and 95% confidence

intervals. The confidence intervals have not been adjusted for

multiplicity, so intervals should not be used to infer definitive

treatment effects. Statistical significance was taken as a two-sided p<0.05. All

analysis was undertaken using R (Version 3.4.3).

8


9


Results

Trial Participants and Follow-up

Between 18th November 2010 and 24th September 2014, we randomized 4,146 patients

with stable chest pain at 12 cardiology centers across Scotland (Figure S1). Baseline

clinical characteristics, coronary CT angiography findings, influence on diagnostic

certainty and subsequent initial management have previously been reported9,10 and are

presented here (Table 1 and Tables S1, S2 and S3). Among patients who remained

registered in Scotland throughout the trial (n=4,080, 98.4%), no patient withdrew

consent, and we had complete data over a median of 4.8 years in both study groups,

comprising 20,254 patient-years of follow-up through January 31, 2018.

Subsequent Management

Compared to baseline treatment, patients undergoing coronary CT angiography were

more likely than standard-care patients to have been commenced on preventative (402

[19.4%] versus 305 [14.7%]; odds ratio [OR] 1.40; 95% confidence interval [CI], 1.19

to 1.65) and anti-anginal (273 [13.2%] versus 221 [10.7%]; OR 1.27; 95% CI, 1.05 to

1.54) therapies. The differences in overall prescribing persisted over 5 years (Table S4).

After 5 years, there was no difference in the frequency of invasive coronary

angiography between the coronary CT angiography and standard-care groups (491

[23.6%] versus 502 [24.2%]; hazard ratio [HR] 1.00; 95% CI, 0.88 to 1.13) (Figure 1A).

Although we had previously seen a trend for increased early coronary revascularization

in the group assigned to coronary CT angiography,9 there was no difference in the

frequency of coronary revascularization between treatment groups at 5 years (279

10


[13.5%] versus 267 [12.9%]; HR 1.07; 95% confidence intervals, 0.91 to 1.27) (Figure

1B). Beyond the first 12 months, patients allocated to coronary CT angiography had

lower rates of invasive coronary angiography (HR 0.70; 95% CI, 0.52 to 0.95) and

coronary revascularization (HR 0.59; 95% CI, 0.38 to 0.90) than those receiving

standard care alone (Figure S2).

Clinical Outcomes

The principal long-term end point (coronary heart disease death or nonfatal myocardial

infarction) was reduced in those patients who underwent coronary CT angiography (48

[2.3%] versus 81 [3.9%]; HR 0.59; 95% CI, 0.41 to 0.84; p=0.004) (Table 2 and Figure

2). This was primarily driven by a reduction in non-fatal myocardial infarction (HR

0.60; 95% CI 0.41 to 0.87) (Table 2). The results for the components of the principal

end point are shown in Table 2.

There was no evidence of heterogeneity of effect for the principal end point across a

range of subgroups (Figure 3) and trial centers (Figure S3). Excluding the first 50 days

to account for the delay in implementing the coronary CT angiography findings,10

landmark analysis provided a similar point estimate for the reduction in the principal

end point (HR 0.53; 95% CI 0.36 to 0.78). Among the 48 patients allocated to coronary

CT angiography who subsequently met the principal end point, 22 patients had

obstructive disease, 17 patients had non-obstructive disease and 3 patients had normal

coronary arteries on their baseline CT scan, and 6 patients had defaulted their coronary

CT angiography appointment.

11


Clinical outcomes were no different whether patients had possible angina or non-

anginal chest pain as defined by the National Institute for Health and Care Excellence

(NICE) guidelines (Supplementary Appendix and Table S5).18-20 Although the 5-year

event rates were higher in patients with possible angina (3.1% versus 1.8%), similar

absolute reductions in the principal end point were evident in those with non-anginal

chest pain (Figure S4).

12


Discussion

In our previous report from the SCOT-HEART trial, we found that use of coronary CT

angiography had a significant impact on the diagnosis and treatment of patients referred

for evaluation of stable chest pain, influencing both the certainty and frequency of

coronary heart disease diagnosis and leading to alterations in patient management.9 We

here report our pre-specified 5-year clinical outcomes,13 finding that the use of coronary

CT angiography, with consequent changes in treatment, significantly reduced the rate of

coronary heart disease death or non-fatal myocardial infarction. Despite apparent initial

increases, we did not observe any differences in the overall use of invasive coronary

angiography and coronary revascularization by 5 years. Our findings suggest that the

use of coronary CT angiography increased the correct identification of patients with

coronary heart disease, thus increasing the use of appropriate therapy, and this change in

management reduced the rate of clinical events.

In both the SCOT-HEART9 and PROMISE11 trials, use of coronary CT angiography

increased the rate of detection of obstructive coronary heart disease as confirmed by

invasive coronary angiography. Patients who are correctly diagnosed with coronary

heart disease are likely to have more appropriate use of invasive coronary angiography

and revascularization;9,11 they are also more likely to be commenced on appropriate

preventative therapies10 and may have greater motivation to implement healthy lifestyle

modifications. In addition, the SCOT-HEART trial encouraged initiation of secondary

prevention in patients with non-obstructive coronary artery disease. Among the group

who underwent coronary CT angiography, approximately half of subsequent myocardial

infarctions occurred in those with non-obstructive disease at baseline. It is likely that

13


this proportion was higher in those receiving standard care alone given that non-

obstructive disease was unrecognised and untreated. In the PROMISE trial, where

preventative therapies were not mandated, two-thirds of subsequent cardiac events

occurred in those with non-obstructive disease.22 Finally, event rates in the two study

groups were similar until diagnoses were confirmed and alterations in treatment were

made after approximately 7 weeks,10 suggesting that the groups were well matched at

baseline and changes in outcome only occurred once treatment interventions directed by

coronary CT angiography were initiated. We hypothesize the immediate reductions in

events were mediated through aspirin23,24 and coronary revascularization procedures,25,26

and that longer-term benefits are attributable to lifestyle modification27 and statin

therapy.28

Previous studies have suggested that coronary CT angiography increases early rates of

both invasive coronary angiography and coronary revascularization.9,11,29 Over the 5-

year follow-up, we found that these early increases in procedure rates were no longer

apparent. We performed landmark analyses at 12 months to distinguish the immediate

effects of coronary CT angiography from the longer-term consequences. We

demonstrated that beyond 12 months, rates of invasive coronary angiography and

coronary revascularization were higher in the standard-care group. This would be

consistent with both the emergence of unrecognized disease and non-fatal myocardial

infarction in the standard-care group, and the reduction in disease progression in the

coronary CT angiography group due to the implementation of lifestyle modification and

preventative therapies.28

14


Some observers have highlighted the low cardiovascular event rates in trials of coronary

CT angiography in patients with stable chest pain, prompting others to suggest that no

testing may be appropriate. In the SCOT-HEART trial, we enrolled patients with a

broad range of cardiovascular risk. Overall, we observed event rates of ~4% over 5

years equating to 8% over 10 years. However, half of the study population had normal

or near-normal coronary arteries, implying that those with non-obstructive or

obstructive coronary heart disease had 10-year event rates of approximately 16%. This

underlines the importance of promptly and accurately identifying the presence of

coronary heart disease.

Strategies to stratify patients before testing have been proposed and are embodied in

current guidelines.4-6 However, these still lead to overtesting due to poor predictive

accuracy of current scores.20,30 Recently, NICE have recommended a simple symptom-

based approach, dichotomising patients into those with non-anginal chest pain and those

with possible angina.19 We demonstrated that patients with possible angina were at

higher risk, especially in the first 3-6 months, which perhaps reflects the inclusion of

patients with recent onset angina pectoris, who constitute a particularly high-risk

group.31,32 However, overall all patients appeared to derive similar benefits from

coronary CT angiography, raising the question of whether more widespread testing may

be helpful irrespective of symptoms. Our data would suggest that 63 patients with stable

chest pain need to be referred for coronary CT angiography to prevent one fatal or non-

fatal myocardial infarction over 5 years.

There are some study limitations that we should acknowledge. First, this was an open-

label trial, and ascertainment bias is inherent to the study design. The risk of

15


ascertainment bias is likely increased by the lack of blinded event adjudication, since

clinical diagnoses were coded with knowledge of the assigned study group. This risk

may however have been mitigated by the fact that the principal long-term end point was

composed of hard clinical events. Second, we do not have data on lifestyle alterations

during follow-up and can only speculate that this may have been greater in the coronary

CT angiography group. Third, cardiovascular risk thresholds to initiate preventative

therapies have fallen since study completion and it is unclear whether the benefits of

coronary CT angiography will be maintained with these lower thresholds. Finally, the

absolute benefit in reducing coronary heart disease death and non-fatal myocardial

infarction (1.6%) may be considered modest, but this absolute benefit is similar to, if

not greater than, those achieved in recent pharmaceutical interventional trials in patients

with established coronary heart disease.33-35

In conclusion, in the SCOT-HEART trial, we found that the use of coronary CT

angiography in patients being referred to the cardiology clinic for assessment of stable

chest pain reduced the subsequent risk of coronary heart disease death or nonfatal

myocardial infarction. This benefit was achieved without long-term increases in the use

of invasive coronary angiography or coronary revascularization.

16


Acknowledgements

The Chief Scientist Office of the Scottish Government (CZH/4/588) funded the trial

with supplementary support from the British Heart Foundation (CH/09/002), Edinburgh

and Lothian’s Health Foundation Trust and the Heart Diseases Research Fund. DEN

(CH/09/002, RE/13/3/30183), MCW (FS/11/014), CB (RE/13/5/30177), NLM

(FS/16/14/32023) and MRD (FS/14/78/31020) are supported by the British Heart

Foundation. MCW is supported by The Chief Scientist Office of the Scottish

Government Health and Social Care Directorates (PCL/17/04). EVB is supported by the

Scottish Imaging Network – A Platform of Scientific Excellence (SINAPSE). The

Royal Bank of Scotland supported the provision of 320-multidetector computed

tomography for NHS Lothian and the University of Edinburgh. The Edinburgh Imaging

(Edinburgh), the Clinical Research Facility Glasgow and the Clinical Research Facility

Tayside are supported by National Health Service Research Scotland (NRS).

Conflicts of Interest

During conduct of the study and within the last 3 years: EvB reports personal fees and

non-financial support from Toshiba Medical Systems.

Outside of the submitted work and relevant to CT: DEN reports grant support from

Siemens. EvB reports support from QCTIS UK Ltd, grants and non-financial support

from Siemens Healthineers, personal fees from InHealth, personal fees from Aidence

NV, personal fees and non-financial support from Imbio. MCW reports support from

GE Healthcare. CB reports non-financial support from HeartFlow, grants from

17


AstraZeneca, other from Philips, other from Menarini, non-financial support from

Siemens Healthcare, grants from Novartis.

Data Sharing

Anonymised data and R code used in the statistical analysis will be made available upon

request to Philip Adamson ([email protected]).

18

mailto:[email protected])


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https://www.ncbi.nlm.nih.gov/pubmed/?term=Daly%20CA%5BAuthor%5D&cauthor=true&cauthor_uid=16415069


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Figure Legends

Figure 1. Cumulative event curves for invasive coronary angiography (upper panel A)

and coronary revascularization (lower panel B) in those assigned to coronary computed

tomography angiography (CCTA; blue) and standard care (red). The number at risk for

each yearly interval is given for each randomised allocation group.

Figure 2. Cumulative event curves for coronary heart disease death or non-fatal

myocardial infarction (upper panel A), and non-fatal myocardial infarction (lower panel

B) in those assigned to coronary computed tomography angiography (CCTA; blue) and

standard care (red). The number at risk for each yearly interval is given for each

randomized allocation group.

Figure 3. Subgroup analyses for the principal end point of coronary heart disease death

or non-fatal myocardial infarction.

CCTA – Coronary Computed Tomography Angiography; CI – Confidence Intervals;

NICE – National Institute for health and Care Excellence; CHD – Coronary Heart

Disease.

*Cardiovascular risk calculated by the ASSIGN Score:14 above and below the median of

15%.

P values were obtained from an interaction term between randomisation arms and the

potential risk factor of interest in a Cox proportional-hazards analysis adjusted for

center and minimization variables. P values are reported without adjustment for

multiplicity of testing.

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Tables

Table 1

Baseline participant characteristics prior to randomisation.

All Participants

Standard Care

Standard Care + CCTA

Number 4146 (100%) 2073 (50%) 2073 (50%)

Demographics

Male 2325 (56%) 1163 (56%) 1162 (56%)Age (years) 57·1±9·7 57·0±9·7 57·1±9·7

Body-mass Index (kg/m2) 29·7±5·9 29·8±6·0 29·7±5·8Atrial Fibrillation 84 (2%) 42 (2%) 42 (2%)

Cardiovascular Risk Factors

Smoking Habit* 2185 (53%) 1090 (53%) 1095 (53%)Hypertension 1395 (34%) 683 (33%) 712 (34%)Diabetes Mellitus 444 (11%) 221 (11%) 223 (11%)Hypercholesterolemia 2176 (53%) 1077 (52%) 1099 (53%)Family History 1716 (41%) 829 (40%) 887 (43%)

History of Prior Coronary Heart Disease

372 (9%) 186 (9%) 186 (9%)

Medications

Anti-platelet Agent 1993 (48%) 984 (48%) 1009 (49%)Statin 1786 (43%) 884 (43%) 902 (44%)Beta-blockade 1357 (33%) 672 (32%) 685 (33%)ACE Inhibitor/ARB 685 (17%) 344 (17%) 341 (16%)Calcium Channel Blocker 377 (9%) 194 (9%) 183 (9%)Nitrates 1160 (28%) 590 (29%) 570 (28%)Other Anti-anginal Therapy 191 (5%) 96 (5%) 95 (5%)

Anginal Symptoms† Typical 1462 (35%) 725 (35%) 737 (36%)Atypical 988 (24%) 486 (23%) 502 (24%)Non-anginal 1692 (41%) 859 (41%) 833 (40%)

Electrocardiogram Normal 3492 (84%) 1735 (84%) 1757 (85%)Abnormal 608 (15%) 316 (15%) 292 (14%)

Stress Electrocardiogram

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Performed 3517 (85%) 1764 (85%) 1753 (85%)Normal 2188 (62%) 1103 (63%) 1085 (62%)Inconclusive 566 (16%) 284 (16%) 282 (16%)Abnormal‡ 529 (15%) 264 (15%) 265 (15%)

Further Investigation 1315 (32%) 633 (31%) 682 (33%)Stress Imaging Radionuclide 389 (9%) 176 (9%) 213 (10%)

Other 30 (1%) 16 (1%) 14 (1%)Invasive Coronary Angiography 515 (12%) 255 (12%) 260 (13%)

Baseline Diagnosis CHD 1938 (47%) 982 (47%) 956 (46%)Angina due to CHD 1485 (36%) 742 (36%) 743 (36%)

n (%) or mean ± standard deviation*Current and ex-smokers†National Institute for health and Care Excellence (NICE) criteriaCCTA, coronary computed tomography angiography; ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; CHD, coronary heart disease.‡Evidence of myocardial ischemiaMissing data [standard care alone, standard care + CCTA]: atrial fibrillation n=4 [3, 1]; prior coronary heart disease n=4 [3, 1]; smoking habit n=7 [5, 2]; hypertension n=41 [20, 21]; hypercholesterolemia n=4 [3, 1]; family history n=43 [21, 22]; angina symptoms n=4 [3, 1]; concomittant therapies n=4 for all [3, 1 for all]; resting electrocardiogram n=46 [22, 24]; exercise electrocardiogram n=18 [10, 8]; exercise electrocardiogram outcome n=234 [121, 113]; further investigations n=6 [4, 2]; stress imaging n=4 [3, 1]; invasive coronary angiography n=4 [3, 1]; baseline diagnosis n=4 for both [3, 1 for both].

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Table 2

Clinical outcomes after a median of 4.8 years.

All Participants Standard Care Standard Care + CCTA

Hazard Ratio§ (95% CI)

Number 4146 (100%) 2073 (50%) 2073 (50%)

CHD Death* or Myocardial Infarction 129 (3.1) 81 (3.9) 48 (2.3) 0.59** (0.41 to 0.84)

CHD Death,* Myocardial Infarction or Stroke 160 (3.9) 97 (4.7) 63 (3.0) 0.65 (0.47 to 0.89)

Cardiovascular Events

Myocardial Infarction 117 (2.8) 73 (3.5) 44 (2.1) 0.60 (0.41 to 0.87)

Stroke 35 (0.8) 20 (1.0) 15 (0.7) 0.74 (0.38 to1.44)

Death

CHD* 13 (0.3) 9 (0.4) 4 (0.2) 0.46 (0.14 to 1.48)

Cardiovascular 17 (0.4) 12 (0.6) 5 (0.2) 0.43 (0.15 to 1.22)

Non-cardiovascular 69 (1.7) 31 (1.5) 38 (1.8) 1.24 (0.77 to 2.00)

All-cause 86 (2.1) 43 (2.1) 43 (2.1) 1.02 (0.67 to 1.55)

Procedures

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Coronary angiography 993 (24.0) 502 (24.2) 491 (23.7) 1.00 (0.88 to 1.13)

Revascularization† 546 (13.2) 267 (12.9) 279 (13.5) 1.07 (0.91 to 1.27)

Percutaneous coronary intervention 431 (10.4) 212 (10.2) 219 (10.6) 1.06 (0.88 to 1.28)

Coronary artery bypass graft surgery 131 (3.2) 62 (3.0) 69 (3.3) 1.12 (0.80 to 1.58)

CCTA - Coronary Computed Tomography Angiography; CHD – Coronary Heart Disease.For composite endpoints, data are for the first event only.§Determined from adjusted Cox regression. The confidence intervals have not been adjusted for multiplicity, so intervals should notbe used to infer definitive treatment effects. *Cause of death was myocardial infarction in all cases**P=0.004†12 patients had PCI followed by CABG, 4 patients had CABG followed by PCI.

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