DIAMOND - Dual Antiplatelet Therapy to Reduce Myocardial Injury

Heart attacks are most commonly caused by rupture of fatty deposits (plaques) within the wall of heart blood vessels. It appears that this process can also frequently occur without causing any symptoms and these events likely explain the development of narrowing within the heart arteries which can subsequently produce symptoms of angina (chest pain).

Previous research has shown a specialised scanner known as a PET (positron emission tomography) scan can identify these recently ruptured plaques in patients without symptoms of a heart attack and these patients have changes on a blood test (troponin) which suggest that they are at higher risk of having a heart attack in the future. This study aims to identify these patients using the PET scan and then see if the markers of increased heart attack risk can be reduced by the use of a blood thinning medication (ticagrelor) which is already a well recognised treatment for people who have suffered a recent heart attack.

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.

Eligibility Criteria:
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.