Effects Of Body Mass Index And Body Weight On Blood Drug Concentration And Platelet Aggregation Rate Of Ticagrelor In Patients With Unstable Angina Pectoris

Objective: To investigate whether body weight and body mass index(BMI)affect dual antiplatelet therapy in patients with unstable angina(UA).The concentrations of ticagrelor and AR-C124910XX(active metabolite of ticagrelor)after DAPT)and their anti-platelet aggregation effect.Methods: A total of 105 patients with unstable angina pectoris were diagnosed after admission.After medical history inquiry and venous blood samples were collected for blood routine and platelet aggregation rate,they were immediately given ticagrelor based dual antiplatelet aggregation therapy.The patient’s past history,combined medication,and surgical treatment during hospitalization were collected,and the body weight and height of the patients on 3 and 30 days after treatment were collected,and the corresponding BMI was calculated.At the same time,blood samples were collected from elbow vein before treatment,3 days and 30 days after treatment for blood routine test,and platelet aggregation rate at different time points after treatment was detected by light turbidimetry.Serum samples were frozen.The blood concentrations of ticagrelor and AR-C124910 XX at different time points were detected by high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS).The correlation analysis method and multivariate linear regression model were used to analyze the effects of body weight and BMI on the plasma concentration of ticagrelor and AR-C124910 XX,and platelet aggregation rate at different time points after DAPT containing ticagrelor.COX multivariate regression analysis was used to analyze the influence of the above indicators on the prognosis.Results: The above indexes were analyzed in 105 patients with UA :1.The body weight after treatment was negatively correlated with the blood concentration of ticagrelor(3d: r=-0.276,p<0.001;30d: r=-0.256,p<0.001).Negatively correlated with the concentration of AR-C124910XX(3d: r=-0.337,p<0.001;30d(r=-0.352,p<0.001).BMI was negatively correlated with the plasma concentration of ticagrelor(3d:r=-0.173,p=0.009;30d: r=-0.162,p=0.015),and negatively correlated with the concentration of AR-C124910XX(3d: r=-0.207,p=0.002;30d: r=-0.202,p=0.002).2.There was no correlation between the blood concentration of ticagrelor and PAR-ADP on day 3 after treatment(r=0.016,p=0.085).There was no correlation with IPA-ADP(r=-0.071,p=0.284).The plasma concentration of ticagrelor at 30 days after treatment was negatively correlated with PAR-ADP(r=-0.335,p<0.001),and positively correlated with IPA-ADP(r=0.320,p<0.001).There was no correlation between AR-C124910 XX concentration and PAR-ADP(r=0.073,p=0.276)or IPA-ADP(r=-0.073,p=0.268)at 3d after treatment.The concentration of AR-C124910 XX was negatively correlated with PAR-ADP(r=-0.226,p=0.001)and positively correlated with IPA-ADP(r=0.208,p=0.002)at 30 days after treatment.3.There was no correlation between body weight and PAR-ADP(r=-0.032,p=0.637)or IPA-ADP(r=0.029,p=0.060)at 3 days after treatment.Body weight at 30 days after treatment was positively correlated with PAR-ADP(r=0.171,p=0.010)and negatively correlated with IPA-ADP(r=-0.163,p=0.015).There was no correlation between BMI and PAR-ADP(r=0.010,p=0.879)or IPA-ADP(r=-0.014,p=0.835)on day 3 after treatment.BMI at 30 days after treatment was positively correlated with PAR-ADP(r=0.217,p=0.001)and negatively correlated with IPA-ADP(r=-0.211,p=0.001).4.Linear correlation analysis showed that the blood concentration of ticagrelor 30 days after treatment had a statistically significant linear relationship with PAR-ADP and IPA-ADP.5.Multivariate COX regression analysis showed that body weight and BMI at different time points after DAPT treatment,ticagrelor and AR-C124910 XX,PAR-ADP and IPA-ADP were not related to the occurrence of ischemic events and bleeding events.Conclusions: Body weight and BMI are factors affecting blood concentrations of ticagrelor and AR-C124910 XX in patients with unstable angina pectoris after DAPT treatment based on ticagrelor,as well as its anti-platelet aggregation effect.The higher the body weight and BMI,the lower the blood concentrations of ticagrelor and AR-C124910 XX,the higher the platelet aggregation rate after treatment,and the reduced inhibitory effect of platelet aggregation function.On the contrary,the blood concentrations of ticagrelor and AR-C124910 XX were higher with smaller body weight and BMI.At the same time,the platelet aggregation rate is lower after treatment,that is,the inhibitory effect of platelet aggregation function is increased.