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. 2023 Mar 27:46:101195.
doi: 10.1016/j.ijcha.2023.101195. eCollection 2023 Jun.

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

Manuel Veas Porlán  1 , Antonio Tello-Montoliu  1 , Cecilia López-García  1 , Pablo Gil-Pérez  1 , Miriam Quintana-Giner  1 , Raquel López-Gálvez  1 , José Miguel Rivera-Caravaca  1 , Francisco Marín  1 , Domingo Pascual Figal  1
Affiliations

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

Manuel Veas Porlán et al. Int J Cardiol Heart Vasc. .

Abstract

Background: 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.

Methods: Patients were divided into two groups based on their estimated renal clearances (eGFR ≥ 60 mL/min and eGFR < 60 mL/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.

Results: 48 patients were recruited (eGFR ≥ 60 mL/min: 35 and eGFR < 60 mL/min: 13). There were no significant differences between the groups in terms of platelet inhibition after the loading or after 7 days 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 6 h of loading (p = 0.042 and 0.08 respectively).

Conclusion: 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 4 h of the loading dose.

Keywords: Chronic; Coronary artery disease; Kidney Failure; Platelet reactivity; Ticagrelor.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Study design.
Fig. 2
Fig. 2
Platelet function profiles of normal and CKD patients over the time, assessed by VerifyNow-P2Y12 system. ACS: acute coronary syndrome, ASA: aspirin. eGRF: estimated glomerular filtration. PD: pharmacodynamics, PK: pharmacokinetics, PRU: Platelet Reactivity Units.
Fig. 3
Fig. 3
AR-C124910XX and ticagrelor plasma levels [ng/mL] over the time in normal and CKD patients.
See this image and copyright information in PMC

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