Cardiac computed tomography (CT) for the Assessment of chest Pain and Plaque: a randomised controlled trial
Coronary artery disease (CAD) is the leading single cause of death in Europe, accounting for 1.92 million deaths per year, killing approximately 1 in 5 persons. CAD is also the most common cause of premature death in the UK; 19% of premature deaths in men and 10% of premature deaths in women are from CAD. Cardiovascular-related treatment accounts for 18% of overall UK healthcare expenditure. The most common presentation of CAD is angina. Patients "who develop new symptoms which their general practitioner thinks might be due to angina" should be referred to a Rapid Access Chest Pain Clinic (RACPC). Unfortunately, approximately 30% of patients who attend RACPCs are either unsuitable candidates for treadmill or perform a sub-optimal non-diagnostic test. This cohort of patients has been found to have an increased risk of death when compared to those who have a diagnostically positive treadmill test, suggesting they are not adequately served by RACPCs using exercise stress tests (ESTs). A recent multicentre publication prospectively determined that one third of patients attending a RACPC were erroneously diagnosed with non-cardiac chest pain when they were in fact found to fulfil the primary end point criteria of admission to hospital with acute coronary syndrome. This information suggests that patients are not well served by RACPCs. Cardiac computed tomography (CCT) can bridge this gap. The 64-slice scanner has been shown to be an adequate tool for the detection of significant coronary stenoses, and has a high negative predictive value, close to 100 percent in excluding CAD. The effectiveness of CCT has been recognised by a recent NICE document that addressed the issue of patients presenting with chest pain. What is unclear however is how cost effective the use of CCT is, especially taking into account the lack of avail appropriate CCT scanners and as such NICE asked for research into this in a NHS setting.
There is a number of high profile blood biomarkers that have been proven to be of value in predicting the presence of CAD. However these biomarkers are not in widespread use and do not, as yet, have a specific function in clinical practise. We wish to assess a number of biomarkers in comparison to the actual presence of CAD seen on CT. The need for this research is again guided by the NICE document, which also asked for work to be completed into what new circulating biomarkers add to initial assessment of patients with chest pain.
Little is known about the rate at which CAD progresses. Furthermore high profiles studies have shown that statins can cause halt plaque progression. All our patients with CAD will need appropriate secondary prevention (implemented by their GP) and a repeat CT scan after 18 months, in order to reassess their plaque burden and gain information about the rate of disease progression.
There will be difference behind the standard of care with EST and that from CCT in terms of patient symptoms and outcome. Data produced from questionnaires, biomarkers, CCT, EST and Intravascular Ultrasound (IVUS). The data will be entered into the clinical trial database and verified for accuracy and completeness. There will be statistical and economical health analysis of the data to try to work out the cost-effectiveness of the two arms.
This will be applied for with Office for Research Ethics Committees Northern Ireland on 28/09/2010 – submission pending
Single-centre observational randomised controlled trial
Primary study design
Secondary study design
Randomised controlled trial
Patient information sheet
Not available in web format, please use contact details below to request a patient information sheet
Coronary artery disease
Patients referred to the RACPC in the Ulster Hospital and not excluded by criteria will be considered for the trial. Once in the trial patients will complete questionnaires, have biomarkers taken and be randomised to EST or cardiac CT. The questionnaires to be used will be the established Seattle Angina and EQ-5D questionnaires which, are designed to assess the patients symptoms and their perceived quality of life. They will be repeated at several points, and will not be altered for this study.
The biomarkers to be used include HDL sub-fractions; HS-CRP; Apolipoprotein A-I; Apolipoprotein A-2; Apolipoprotein B; Apolipoprotein(a) precursor (LPA); Homocysteine; HbA1C; Serum Testosterone; Sex hormone-binding globulin (SHBG); Fasting Insulin.; Lipid soluble anti-oxidants; Ascorbic Acid; Lipoprotein and enzyme status; Serum Amyloid A; Cholesterol ester transfer protein; Interleukin-1; Interleukin-6; Interleukin-10; Alpha Tumor necrosis factor; Lipid Hydroperoxide; F2-isoprostanes; Hepatic lipase.
These will be performed to standard NHS/University protocol.
Primary outcome measures
Change in scores from baseline at 3 months on the physical limitation scale of the SAQ-UK
Secondary outcome measures
1. The cost effectiveness of cardiac CT as a primary diagnostic strategy will be compared with the costs associated with the current standard of care
2. Health-related quality of life
3. Cumulative radiation exposure
4. Resource utilisation
Overall trial start date
Overall trial end date
Participant inclusion criteria
1. Patients over 40 referred to the Rapid Access Chest Pain Clinic (RACPC), Ulster Hospital, Northern Ireland for suspicion of angina
2. Patients must have the ability to hold breath
Target number of participants
Participant exclusion criteria
1. Less than 40 years of age
2. Significant renal dysfunction with an estimated Glomerular Filtration Rate (eGFR) less than 35. As the contrast used in CCT and conventional angiography can cause contrast nephropathy these patients with will be excluded from the study
3. Recent history of alcohol, drug abuse, or other medical conditions that might compromise safety, successful completion of, or drug compliance during the study
4. Patients with a history of chronic inflammatory conditions, such as severe arthritis, lupus, or inflammatory bowel disease, as well as subjects taking immunosuppressant agents, such as cyclosporine, tacrolimus, azathioprine, or chronic oral glucocorticoids. Because High-Sensitivity C-Reactive Protein (hs-CRP) will be measured, patients with other conditions that may cause a chronically elevated CRP will be excluded.
5. Unstable angina pectoris
6. Uncontrolled fast atrial fibrillation or other arrhythmias that may interfere with ECG-gated triggering of CT
7. Patients with extreme tachycardia, greater than 110 bpm, despite rate controlling agents
9. Morbid obesity (Body Mass Index [BMI] >35)
10. Known contrast medium allergy
11. Known ischaemic heart disease with previous intervention in the form of coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI)
12. Inability to lie flat.
13. Severe Aortic Stenosis (clinically suspected and confirmed by echocardiogram)
14. Acute myocarditis/pericarditis
15. Uncontrolled hypertension >220/100
16. Severe peripheral vascular disease or impaired immobility
17. Severe mental disability that would impair capacity to consent
18. Significant COPD that would impair exercise or B blocker use
19. Left bundle branch
Recruitment start date
Recruitment end date
Countries of recruitment
Trial participating centre
Ulster Hospital (UK)
C/o Paul Carlin
Upper Newtownards Road
Ulster Hospital (UK) - Research Grant (ref: SET/10/52)
Funding Body Type
Funding Body Subtype
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting