Impact of renal function on Ticagrelor-induced antiplatelet effects in coronary artery disease patients.

Abstract

Chronic renal failure (CKD) is associated with the presence of increased platelet reactivity and lower clinical benefit of clopidogrel. Ticagrelor has a more favorable pharmacodynamic and pharmacokinetic profile compared to clopidogrel, which has translated into better clinical outcomes in patients with acute coronary syndrome (ACS). We conducted a prospective mechanistic cohort study in order to investigate the impact of renal failure on the pharmacokinetics and pharmacodynamics of ticagrelor in patients with acute ACS. Patients were divided into two groups based on their estimated renal clearances (eGFR≥60mL/min and eGFR<60mL/min). Platelet function was determined using the VerifyNow system at baseline, after the ticagrelor loading dose and at discharge. In addition, levels of ticagrelor and its active metabolite (AR-C124910XX) were determined in the first hour after loading dose. 48 patients were recruited (eGFR≥60mL/min: 35 and eGFR<60mL/min: 13). There were no significant differences between the groups in terms of platelet inhibition after the loading or after 7days of treatment (p=0.219). However, the levels of ticagrelor and its active metabolite were lower in subjects with normal renal function than in CKD, especially at 4 (p=0.02 and 0.04 respectively) and 6h of loading (p=0.042 and 0.08 respectively). No differences in platelet inhibition were observed after treatment with ticagrelor in patients with different renal function, although patients with renal impairment showed higher levels of ticagrelor and AR-C124910XX after 4h of the loading dose.