This study aims to investigate the effect of early CTCA in patients with suspected or confirmed Acute Coronary Syndrome (ACS) presenting to the Emergency Department (ED) or Medical Assessment Unit (MAU), upon interventions, event rates and health care costs in a pragmatic clinical trial and economic evaluation up to 1 year after the trial intervention. The primary objective will be to investigate the effect of the intervention on all-cause death or subsequent type 1 or type 4b MI at one year, measured as time to first such event.

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