Impact of Renal Function on Ticagrelor-Induced Antiplatelet Effects in Coronary Artery Disease Patients (Ticagrelor)

Dual antiplatelet therapy consisting in aspirin and clopidogrel is the cornerstone of the treatment of the prevention of the thrombotic events in patients with coronary artery disease (CAD), showing a reduction in adverse events . However, there is a considerable number of patients who continue to have recurrent ischemic events despite this regimen . In fact, in the last years several clinical factors have been associated with impaired clopidogrel-induced effects. Moreover, these clinical factors are strongly related with the presence of high on-treatment platelet reactivity (HPR), which is also associated with the occurrence of adverse thrombotic events, including stent thrombosis, despite correct treatment compliance. Diabetes mellitus, acute coronary syndromes, obesity or chronic kidney disease (CKD) are common examples . This observation encourages the search for new more potent antiplatelet therapies. A new P2Y12 receptor antagonist, ticagrelor, has been approved for clinical use . Ticagrelor is a new non-thienopyridine, a cyclopentyltriazolo-pyrimidine (CPTP), direct acting reversible P2Y12 antagonist. This compound has a more favorable pharmacokinetic (PK) and pharmacodynamics (PD) profile than clopidogrel , which has translated into better clinical outcomes in patients with acute coronary syndrome (ACS) in a recent large, international clinical trial . Interestingly, ticagrelor has showed an impressive clinical benefit in patients with CKD in comparison with those patients without renal impairment .

CKD is highly associated with an increased risk of atherothrombotic events, including stent thrombosis, in patients with CAD . PD studies have shown that patients with impaired renal function are characterized by reduced clopidogrel-induced antiplatelet effects and higher rates of HPR compared with patients with preserved renal function.