Comparison of bioavailability and antiplatelet action of ticagrelor in patients with ST-elevation myocardial infarction and non-ST-elevation myocardial infarction: A prospective, observational, single-centre study

BackgroundData from available studies suggest that the presence of ST-elevation myocardial infarction (STEMI) may be associated with delayed and attenuated ticagrelor bioavailability and effect compared with non-ST-elevation myocardial infarction (NSTEMI).MethodsIn a single-center, prospective, observational trial 73 patients with myocardial infarction (STEMI n = 49, NSTEMI n = 24) underwent a pharmacokinetic and pharmacodynamic assessment after a 180 mg ticagrelor loading dose (LD). Ticagrelor and its active metabolite (AR-C124910XX) plasma concentrations were determined with liquid chromatography tandem mass spectrometry, and their antiplatelet effect was measured with the VASP assay and multiple electrode aggregometry.ResultsDuring the first six hours after ticagrelor LD, STEMI patients had 38% and 34% lower plasma concentration of ticagrelor and AR-C124910XX, respectively, than NSTEMI (ticagrelor AUC(0–6): 2491 [344–5587] vs. 3991 [1406–9284] ng*h/mL; p = 0.038; AR-C124910XX AUC(0–6): 473 [0–924] vs. 712 [346–1616] ng*h/mL; p = 0.027). STEMI patients also required more time to achieve maximal concentration of ticagrelor (tmax: 4.0 [3.0–12.0] vs. 2.5 [2.0–6.0] h; p = 0.012). Impaired bioavailability of ticagrelor and AR-C124910XX seen in STEMI subjects was associated with diminished platelet inhibition in this group, which was most pronounced during the initial hours of treatment.ConclusionsPlasma concentrations of ticagrelor and AR-C124910XX during the first hours after ticagrelor LD were one third lower in STEMI than in NSTEMI patients. This reduced and delayed ticagrelor bioavailability was associated with weaker antiplatelet effect in STEMI.Clinical trial registrationClinicalTrials.gov identifier: NCT02602444 (November 09, 2015)背景 现有研究数据表明，与非ST段抬高型心肌梗死（non-ST-elevation myocardial infarction, NSTEMI）相比，ST段抬高型心肌梗死（ST-elevation myocardial infarction, STEMI）患者的替格瑞洛（ticagrelor）生物利用度及药效可能存在延迟与减弱的情况。 方法 本研究为单中心前瞻性观察性试验，共纳入73例心肌梗死患者（STEMI组n=49，NSTEMI组n=24），所有受试者在接受180mg替格瑞洛负荷剂量（loading dose, LD）后，均接受了药代动力学与药效学评估。采用液相色谱-串联质谱法（liquid chromatography tandem mass spectrometry）测定替格瑞洛及其活性代谢产物（AR-C124910XX）的血浆浓度，并通过血管扩张刺激磷蛋白试验（VASP assay）与多电极聚集仪（multiple electrode aggregometry）检测其抗血小板效果。 结果 在替格瑞洛负荷剂量给药后的最初6小时内，STEMI组患者的替格瑞洛与AR-C124910XX血浆浓度分别较NSTEMI组低38%与34%：替格瑞洛的AUC(0–6)分别为2491 [344–5587]与3991 [1406–9284] ng*h/mL，p=0.038；AR-C124910XX的AUC(0–6)分别为473 [0–924]与712 [346–1616] ng*h/mL，p=0.027。此外，STEMI组患者达到替格瑞洛最大血浆浓度的时间更长（tmax：4.0 [3.0–12.0] vs 2.5 [2.0–6.0] h，p=0.012）。本研究中观察到STEMI患者的替格瑞洛与AR-C124910XX生物利用度受损，与其血小板抑制作用减弱相关，该现象在治疗初始数小时内最为显著。 结论 替格瑞洛负荷剂量给药后的最初数小时内，STEMI组患者的替格瑞洛与AR-C124910XX血浆浓度较NSTEMI组低约三分之一。这种生物利用度的降低与延迟，与STEMI患者更弱的抗血小板效果相关。 临床试验注册 临床试验.gov注册号：NCT02602444（2015年11月9日）