Rapid Assessment of Potential Ischaemic Heart Disease With CTCA

DESIGN: Open parallel group randomised controlled trial of early computed tomography coronary angiography (CTCA) in patients presenting with suspected/confirmed acute coronary syndrome (ACS) to Emergency Departments (ED) and Medical Assessment Units.

SETTING: 37 EDs, radiology, cardiology and acute medical services in tertiary/district general National Health Service (NHS) hospitals.

TARGET POPULATION: Inclusion Criteria: Patient ≥18 years with symptoms mandating investigation for suspected or confirmed ACS with at least one of: ECG abnormalities e.g. ST segment depression >0.5 mm; History of ischaemic heart disease (where the clinician assessing patient confirms history based on patient history or available records); Troponin elevation above the 99th centile of the normal reference range or increase in high sensitivity troponin meeting European Society of Cardiology criteria for 'rule-in' or myocardial infarction (NB troponin assays will vary from site to site; local laboratory reference standards will be used). Exclusion Criteria: 1.Signs, symptoms, or investigations supporting high-risk ACS: ST elevation MI; ACS with signs or symptoms of acute heart failure or circulatory shock; Crescendo episodes of typical anginal pain; Marked or dynamic ECG changes e.g. ST depression of >3 mm; Clinical team have scheduled early invasive coronary angiography on day of trial eligibility assessment. 2. Patient inability to undergo CT: Severe renal failure (serum creatinine >250 µmol/L or estimated glomerular filtration rate <30 mL/min); Contrast allergy; Beta blocker intolerance (if no alternative heart rate limiting agent available/suitable) or allergy; Inability to breath hold; Atrial fibrillation (where mean heart rate is anticipated to be greater than 75 beats per minute after beta blockade). 3. Patient has had invasive coronary angiography or CTCA within last 2 years and the previous investigation revealed obstructive coronary artery disease, or patient had either investigation within the last 5 years and the result was normal. 4.Previous recruitment to the trial; 5.Known pregnancy or currently breast feeding; 6. Inability to consent; 7.Further investigation for ACS would not in the patient's interest, due to limited life expectancy, quality of life or functional status; 8.Prisoners

HEALTH TECHNOLOGIES BEING ASSESSED: Early use of ≥64-slice CTCA as part of routine assessment compared to standard care.

MEASUREMENT OF COSTS/OUTCOMES: Primary end-point will be one-year all-cause death or subsequent type 1 or type 4b MI at one year, measured as time to first such event. Secondary endpoints: Key Secondary Endpoints : 1. Coronary Heart Disease (CHD) death or subsequent non-fatal MI; 2. Cardiovascular Disease (CVD) death or subsequent non-fatal MI; 3. Subsequent non-fatal MI; 4.Coronary Heart Disease death; 5. Cardiovascular death; 6. All-cause death. Other Endpoints; Coronary

Heart Disease (CHD) death or subsequent non-fatal MI (type 1 or 4b);Subsequent Non-fatal MI (type 1 or 4b); Non-cardiovascular death; Invasive coronary angiography; Coronary revascularisation; Percutaneous coronary intervention; Coronary artery bypass graft; Proportion of patients prescribed ACS therapies during index hospitalisation; Proportion of patients discharged on preventative treatment or have alteration in dosage of preventative treatment during index hospitalisation; Length of stay for index hospitalisation; Representation or rehospitalisation with suspected ACS/recurrent chest pain within 12 months after index hospitalisation; Chest pain symptoms up to 12 months; Patient satisfaction at 1 month; Clinician certainty of presenting diagnosis after CTCA; Quality of Life (measured by EQ- 5D-5L up to12 months). Adverse Events and Serious Adverse Events; Proportion of patients with alternative cardiovascular diagnoses identified on CTCA; Proportion of patients with non-cardiovascular diagnosis identified on CTCA; Radiation exposure from CTCA as trial intervention. Cost effectiveness:

Estimated in terms of the lifetime incremental cost per quality-adjusted life year (QALY) gained.

SAMPLE SIZE: 1,749 patients (1,748 available for analysis).

Inclusion criteria

Patient ≥18 years with symptoms mandating investigation for suspected or confirmed ACS with at least one of:

• ECG abnormalities e.g. ST segment depression >0.5 mm;
• History of ischaemic heart disease (where the clinician assessing patient confirms history based on patient history or available records);
• Troponin elevation above the 99th centile of the normal reference range or increase in high sensitivity troponin meeting European Society of Cardiology criteria for 'rule-in' or myocardial infarction (NB troponin assays will vary from site to site; local laboratory reference standards will be used).

Exclusion criteria

• Signs, symptoms, or investigations supporting high-risk ACS:

• ST elevation MI;
• ACS with signs or symptoms of acute heart failure or circulatory shock;
• Crescendo episodes of typical anginal pain;
• Marked or dynamic ECG changes e.g. ST depression of >3 mm
• Clinical team have scheduled early invasive coronary angiography on day of trial eligibility assessment.
• Patient inability to undergo CT:

• Severe renal failure (serum creatinine >250 µmol/L or estimated glomerular filtration rate <30 mL/min);
• Contrast allergy;
• Beta blocker intolerance (if no alternative heart rate limiting agent available/suitable) or allergy ;
• Inability to breath hold;
• Atrial fibrillation (where mean heart rate is anticipated to be greater than 75 beats per minute after beta blockade).
• Patient has had invasive coronary angiography or CTCA within last 2 years and the previous investigation revealed obstructive coronary artery disease, or patient had either investigation within the last 5 years and the result was normal.
• Previous recruitment to the trial;
• Known pregnancy or currently breast feeding;
• Inability to consent;
• Further investigation for ACS would not in the patient's interest, due to limited life expectancy, quality of life or functional status;
• Prisoners