DIAMOND - Dual Antiplatelet Therapy to Reduce Myocardial Injury

The investigators aim to recruit patients with multivessel, clinically stable coronary artery disease. Patients will undergo baseline investigations including CT-PET imaging using 18F-Sodium Fluoride (18F-F) tracer to detect potentially unstable coronary plaques. The groups will be separated into those with and without 18F-F uptake. Each of these groups will be randomised to receive oral ticagrelor or a matched placebo in addition to their usual medications. Patients will remain on aspirin but will not be eligible for the trial if taking additional antiplatelet/anticoagulant treatments. The treatment will be continued for 1 year.

Inclusion criteria

• Patients aged ≥40 years with angiographically proven multivessel coronary artery disease defined as at least two major epicardial vessels with any combination of either (a) >50% luminal stenosis, or (b) previous revascularization (percutaneous coronary intervention or coronary artery bypass graft surgery).
• Provision of informed consent prior to any study specific procedures

Exclusion criteria

• An acute coronary syndrome within the last 12 months
• An indication for dual anti-platelet therapy, such as drug eluting stent
• Inability to take aspirin
• Receiving thienopyridine therapy such as clopidogrel or prasugrel
• Percutaneous coronary intervention or coronary artery bypass graft surgery within the last 3 months
• Inability or unwilling to give informed consent
• Woman with child-bearing potential and who are breastfeeding will not be enrolled into the trial (woman who have experienced menarche, are pre-menopausal, have not been sterilised or who are currently pregnant)
• Known hypersensitivity to ticagrelor or one of its excipients
• Active pathological bleeding or bleeding diathesis
• Significant thrombocytopenia: <100 x 10^9 /L
• History of intracranial haemorrhage
• Moderate to severe liver impairment (Child's Grade B or C)
• Maintenance therapy with strong cytochrome P450 3A4 (CYP3A4) inhibitors, such as ketoconazole, nefazodone, ritonavir, indinavir, atazanavir, or clarithromycin
• Major intercurrent illness or life expectancy <1 year
• Renal dysfunction (eGFR ≤30 mL/min/1.73 m2)
• Contraindication to iodinated contrast agents
• Planned coronary revascularization or major non-cardiac surgery in the next 12 months
• Maintenance therapy with simvastatin at doses greater than 40mg daily
• Receiving oral anticoagulants including warfarin, rivaroxaban, dabigatran or apixaban.