Peripheral Endothelial Function Assessment of Patients on Ticagrelor vs. Clopidogrel Who Have Undergone Percutaneous Coronary Intervention - a Randomised, Crossover Study.

Cardiovascular disease remains the most common cause of death in Ireland. Usage of antiplatelet agents and cardiac procedures such as coronary angioplasty has dramatically improved the morbidity and mortality associated with coronary artery disease. In patients with a coronary stent, dual antiplatelet therapy is recommended. Aspirin is the main antiplatelet agent used. For many years, clopidogrel was the second antiplatelet of choice. Recent studies have revealed new antiplatelet drugs that can substitute clopidogrel, one of which is ticagrelor. Ticagrelor received approval from regulatory authorities such as the Food and Drug Administration and the European Medicines Agency based on the PLATO trial which demonstrated a reduction in overall mortality and thrombotic cardiovascular events when compared to clopidogrel. Ticagrelor is approved in Europe and specifically in Ireland for use in patients with ACS and in patients undergoing coronary angioplasty. The degree to which ticagrelor reduced the overall mortality compared to clopidogrel in the PLATO trial suggested that ticagrelor possibly has a pleiotropic effect and that the reduction in mortality is not simply due to its antiplatelet effects. The ticagrelor molecule resembles adenosine. It has been shown that ticagrelor increases adenosine concentration, by interfering with its red blood cells' uptake and by inducing the release of ATP which is then converted to adenosine. Adenosine has been shown to be cardioprotective.

Peripheral Arterial Tonometry (EndoPAT 2000 system (Itamar Medical, Caesarea, Israel) is a method for evaluating endothelial dysfunction. The device has received a CE mark (approved for use in Europe). It uses a non-invasive assessment called fingertip pulse amplitude tonometry.

The reactive hyperaemia response as detected by the reactive hyperaemia index (RHI) has been shown to be related to multiple traditional and metabolic risk factors. It has also been found to positively correlate with flow mediated dilatation (FMD) and coronary vasoreactivity as assessed by intracoronary acetylcholine. A significant advantage of the endoPAT device is the reproducibility of results when compared to FMD in assessment of peripheral endothelial function. Smaller studies have shown positive effects of ticagrelor on endothelial function assessment compared with clopidogrel or prasugrel but no randomised study has been done to date.

The aim of this project is to study the effects of ticagrelor on the arterial system using a noninvasive method. The study will employ the measurement of peripheral endothelial function of patients who undergo percutaneous coronary intervention who are on ticagrelor vs. clopidogrel using a cross over trial design.