Diagnostic Imaging Strategies for Patients with Stable Chest Pain and Intermediate Risk of Coronary Artery Disease: Extended Follow-up (DISCHARGE–Extend)

• Applicant: Professor Dr. Marc Dewey
• Subject Area: Radiology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 551186137

Background and Objectives: Computed tomography (CT) is an accurate noninvasive alternative to invasive coronary angiography (ICA). In the European multicentre randomised controlled DISCHARGE trial of 3561 patients with stable chest pain and intermediate probability of obstructive coronary artery disease (CAD), CT was a safer first line investigation than ICA without significant differences in major adverse cardiovascular events (MACE). Methods and Work Programme: Although the primary outcome of MACE was not significantly different in DISCHARGE at 3.5 years of follow-up, there was an apparent trend for the CT group to have a lower MACE rate: Hazard ratio (HR) of 0.7 (95% CI, 0.46-1.07; P=0.10). We propose to extend the follow-up of DISCHARGE to 8.5 years which will have 80% power to detect a difference between the CT and ICA groups if the relative effect size remains unchanged. This extended follow-up will also facilitate further insight into the development of CAD by investigating the following secondary hypotheses in addition to the primary MACE hypothesis. First, in the single-centre CAD-Man study, lower cholesterol concentrations were observed at follow-up in the CT group. As lipid levels are strongly associated with coronary plaque growth, we will perform CT at follow-up in both randomisation groups to investigate whether quantitative coronary CT plaque measures will show a lower burden in the CT group compared to the ICA group. Second, we hypothesise that low-density lipoprotein cholesterol will be lower in the CT group at the extended follow-up of 8.5 years. Third, in accordance with the recommendation of the DFG Clinical Trials Review Panel, we will assess overall survival in both randomisation groups. Fourth, better cardiovascular risk factor modification and medications could be associated with reduced intraindividual coronary plaque progression on CT in the CT group. Additionally, secondary analysis of the CAD-Man study showed that patients who received an intravenous contrast agent for CT had a lower rate of acute kidney injury than patients who received an intra-arterial contrast agent for ICA. Therefore, the safety hypothesis is that chronic renal function impairment is less likely to occur in the CT group than in the ICA group at long-term follow-up. The power calculation was performed based on the HR observed for MACE, and the annual drop-out rate (0.31%) was based on the actual drop-out rate observed in DISCHARGE. The design and protocol of DISCHARGE-Extend follows CONSORT and has been planned in collaboration with the patient interest group and the 26 clinical recruitment centers that have all agreed to participate. Anticipated Gain of Knowledge: We expect to gain new insights into the long-term clinical consequences of CT-guided diagnostic management in patients with intermediate probability of stable obstructive CAD. It can be anticipated that DISCHARGE-Extend will exhibit a potential analogous to that of SCOT-HEART Extend.

• DFG Programme: Clinical Trials