Effects of Body Mass Index and Body Weight on Plasma Concentration of Ticagrelor and Platelet Aggregation Rate in Patients with Unstable Angina in a Chinese Han Population

TL;DR

This study shows that higher body weight and BMI in Chinese patients with unstable angina are linked to lower ticagrelor drug levels and less effective anti-platelet effects.

Contribution

The study identifies BMI and body weight as significant factors affecting ticagrelor pharmacokinetics and platelet inhibition in a Chinese Han population.

Findings

Higher BMI and body weight correlate with lower ticagrelor and metabolite concentrations at 3 and 30 days post-treatment.

BMI and body weight are positively linked to platelet aggregation rates at baseline and 30 days after treatment.

Both BMI and body weight show negative correlations with platelet aggregation inhibition at 30 days post-treatment.

Abstract

The aim of this study was to investigate the impact of body
mass index (BMI) and body weight on the concentrations of ticagrelor and the
ticagrelor metabolite, AR-C124910XX, as well as the platelet aggregation rate
(PAR) in a Chinese Han population with unstable angina (UA). Specifically, it
focused on these parameters following the administration of dual antiplatelet
therapy (DAPT) comprising aspirin and ticagrelor.

A total of
105 patients with UA were included in the study. Measurement of the platelet
aggregation rate induced by adenosine diphosphate (PAR-ADP) was performed before,
as well as 3 and 30 days after DAPT treatment. The plasma concentrations of
ticagrelor and AR-C124910XX were detected at 3 and 30 days after DAPT treatment.
We conducted correlation analyses to assess the effects of BMI and body weight on
the concentrations of ticagrelor and AR-C124910XX, on PAR-ADP, and on the
inhibition of platelet aggregation induced by adenosine diphosphate (IPA-ADP) at
both 3 and 30 days after DAPT treatment.

The BMI and body
weight were positively correlated with baseline PAR-ADP (r = 0.205,
p = 0.007; r = 0.122, p = 0.022). The PAR-ADP at 3 and
30 days after DAPT treatment were significantly lower than at baseline (61.56%
± 10.62%, 8.02% ± 7.52%, 12.90% ± 7.42%, p
<
0.001). There was a negative correlation between body weight and the
concentrations of ticagrelor and AR-C124910XX at 3 days following DAPT treatment
(r = –0.276, p
< 0.001; r = –0.337, p
<
0.001). Additionally, BMI showed a similar negative correlation with the
concentrations of ticagrelor and AR-C124910XX (r = –0.173, p =
0.009; r = –0.207, p = 0.002). At 30 days after treatment, both
body weight and BMI were negatively correlated with ticagrelor (r =
–0.256, p
< 0.001; r = –0.162, p = 0.015) and its
metabolite (r = –0.352, p
< 0.001; r = –0.202,
p = 0.002). Body weight was positively correlated with PAR-ADP
(r = 0.171, p = 0.010) and negatively correlated with IPA-ADP
(r = –0.163, p = 0.015) at 30 days after treatment. Similarly,
BMI was positively correlated with PAR-ADP (r = 0.217, p =
0.001) and negatively correlated with IPA-ADP (r = –0.211, p =
0.001) at the same time point.

BMI and body weight are key
factors influencing the pharmacokinetics and pharmacodynamics of ticagrelor in
Chinese Han patients with UA following DAPT treatment that includes ticagrelor.
Both BMI and body weight were positively correlated with PAR-ADP at baseline and
30 days after DAPT treatment.

ChiCTR2100044938,
https://www.chictr.org.cn/.

Figures