The pharmacodynamics of low and standard doses of ticagrelor in patients with end stage renal disease on hemodialysis

Abstract

Background: Patients with end-stage renal disease (ESRD) on maintenance hemodialysis (HD) respond poorly to clopidogrel. We assessed the utility of low-dose ticagrelor in ESRD patients on maintenance HD.

Methods: In this single-center, prospective, randomized pharmacodynamic study, 52 ESRD patients on HD were prescribed clopidogrel (300mg loading dose [LD], then 75mg daily), standard-dose ticagrelor (180mg LD, then 90mg twice daily), or low-dose ticagrelor (90mg LD, then 90mg daily) for 14days. Platelet function was evaluated before and after therapy via light transmittance aggregometry and the VerifyNow™ P2Y₁₂ assay.

Results: The adenosine diphosphate (ADP)-induced maximal extent of platelet aggregation differed significantly between the low-dose ticagrelor and clopidogrel groups (ANCOVA, p=0.04 after stimulation with 5μmol/L ADP; p<0.01 after stimulation with 20μmol/L ADP). Inhibition of platelet aggregation increased significantly in the order of clopidogrel, low-dose ticagrelor, and standard-dose ticagrelor, as revealed by adjusted intergroup comparison analysis (ANCOVA, p=0.04 after stimulation with 5μmol/L ADP; p=0.005 after stimulation with 20μmol/L ADP). The rates of onset of the antiplatelet effect curves from 0 to 5h after administration of the LDs were greater in the standard- and low-dose ticagrelor groups than in the clopidogrel group. Significant sequential reductions in P2Y₁₂ reaction units were noted, in the following order: clopidogrel, low-dose ticagrelor, and standard-dose ticagrelor (ANCOVA, p<0.001). No bleeding occurred in the low-dose ticagrelor group.

Conclusions: Low-dose ticagrelor afforded greater platelet inhibition than did clopidogrel in ESRD patients on HD.

Keywords: Clopidogrel; End stage renal disease; Hemodialysis; Platelet; Ticagrelor.