TRACTION is an investigator-driven, prospective, parallel-group, randomized, open-label, assessor-blinded (PROBE), multicenter, noninferiority trial (Clinicaltrials.gov: NCT06101862 ). A total of 2,300 patients with a working diagnosis of NSTE-ACS (inclusion criteria of elevated troponins and/or ischemic ECG changes) will be randomized to CCTA and team-based interventional triage vs standard of care with ICA (control group). Primary exclusion criteria include high risk clinical features requiring immediate ICA (including persistent chest pain and hemodynamic instability ), history of PCI or CABG, or probable type 2 acute myocardial infarction. Patients are currently recruited from all cardiology departments in the eastern part of Denmark (The Capital Region of Copenhagen and Region Zealand). Both sites with and without invasive capabilities participate. Sites are encouraged to recruit patients throughout the week, provided that randomization to CCTA does not cause a substantial delay due to limited CCTA availability. Figure 1 shows the trial flowchart and Table 1 the full list of inclusion and exclusion criteria.

Trial flowchart. NSTE-ACS, non-ST elevation acute coronary syndrome.

In the intervention group, patients will undergo CCTA as soon as possible during hospitalization. The CCTA will be reviewed by a multidisciplinary Coronary Team consisting of interventional and CT specialized cardiologists taking clinical presentation and patient characteristics into account to determine the need for revascularization.

In the control group, patients will undergo standard of care with conventional ICA as soon as possible during hospitalization (preferably within 24 to 48 hours), with treatment decisions based on the ICA findings.

The primary endpoint is major adverse cardiac events at 1 year (all-cause mortality, nonfatal myocardial infarction, hospitalization with refractory angina, or hospitalization with heart failure), from the time of randomization.

As soon as a working diagnosis of NSTE-ACS is established with a usual indication for ICA, and when informed written consent has been obtained, patients will be randomized 1:1 using a web-based central randomization system (REDCap). Block randomization with random block sizes of 2, 4, and 6 will be used. The trial is open-labelled with blinded outcome assessment (see later section).

Patients randomized to the intervention group will undergo local CCTA at the site of randomization as quickly as possible after randomization. An ECG-gated calcium score and contrast enhanced CCTA will be performed in all cases, regardless of calcium score. The CCTA will be conducted with contemporary, local available scanners and scan protocols. All sites have been instructed to prioritize scan quality (ie, scanning at a wider RR-interval or a higher tube voltage) even at the cost of total radiation dose. Heart rate will be reduced using beta-blockers or other rate-reducing drugs if needed according to local protocols, and sublingual nitroglycerin will be used.

CCTAs will be reported according to the Society of Cardiovascular CT guidelines and the American Heart Association coronary artery segment model. ^, Severity of coronary atherosclerotic disease will be characterized as no obstructive disease (diameter stenosis <50%), 50% to 69% stenosis, 70% to 99% stenosis, total occlusion, or total occlusion-presumed chronic. Analysis will be performed by a cardiologist specialized in CCTA shortly after the scan has been completed.

After the CCTA has been analyzed, an ad hoc Coronary Team conference will be conducted to review the imaging results and determine further treatment strategy. The Coronary Team consists of the local CCTA specialist, and an interventional cardiologist and a CCTA specialist from the invasive center. Locally acquired CCTA imaging data will be transferred digitally to be available for 3D-reconstructive analysis at the invasive center, and screen sharing during the conference will allow discussion of imaging findings. The Coronary team will have access to all relevant patient information. To determine further management, both CCTA findings and patient-specific clinical information will be considered. The conference decision for preferred management will be either medical treatment, PCI, or CABG.

If the CCTA shows obstructive disease in 1 or more important coronary arteries or branches (generally defined as vessels with diameter ≥2.5 mm), the Coronary Team will determine whether PCI is indicated, also considering technical suitability, clinical, and paraclinical findings. If PCI is recommended by the Coronary Team, the patient will be transferred to the invasive center. CCTA images are used by the interventional cardiologist to plan and guide the procedure. Invasive angiography of arteries conclusively without significant disease on CCTA is not mandatory. PCI is performed according to best practice, using the same techniques, anticoagulants, and intravascular imaging in complex cases as in the control group. In case CABG is expected to be the best treatment, ICA will be performed and subsequently Heart Team conference with cardiac surgeons, to discuss the option of surgical revascularization.

In patients with obstructive disease on the CCTA but where revascularization is considered not indicated or not feasible, or in patients with nonobstructive disease, the Coronary Team will recommend guideline-directed medical treatment. In patients with no coronary disease, the Team may recommend additional diagnostic tests. If the CCTA findings are inconclusive, the patient will undergo ICA at an invasive center to clarify the diagnosis and guide treatment.

Both CCTA and ICA involve ionizing radiation with comparable overall exposure levels (approximately 3 mSv for CCTA and 3.5 mSv for ICA). Participants randomized to CCTA who subsequently require revascularization may receive an additional average dose of about 3 mSv compared to those randomized to ICA.