Low-dose ticagrelor yields an antiplatelet efficacy similar to that of standard-dose ticagrelor in healthy subjects: an open-label randomized controlled trial

• Published in: Scientific reports Vol. 6; no. 1; p. 31838
• Main Authors: Li, Pan, Gu, Ying, Yang, Yawei, Chen, Lizhi, Liu, Junmei, Gao, Lihong, Qin, Yongwen, Cai, Quancai, Zhao, Xianxian, Wang, Zhuo, Ma, Liping
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 24.08.2016; Nature Publishing Group
• Subjects: 631/154/109/1940; 631/154/436/108; 631/154/436/1729; 631/154/436/2388; Adenosine - administration & dosage; Adenosine - analogs & derivatives; Adenosine - pharmacokinetics; Adult; Anticoagulants; Bleeding; Blood platelets; Cardiovascular disease; China; Clinical trials; Clopidogrel; Dose-Response Relationship, Drug; Drug dosages; Drug therapy; Electron tubes; Female; Healthy Volunteers; Hospitals; Humanities and Social Sciences; Humans; Male; multidisciplinary; Pharmacokinetics; Platelet Aggregation Inhibitors - administration & dosage; Platelet Aggregation Inhibitors - pharmacokinetics; Receptors, Purinergic P2Y12 - metabolism; Science; Ticagrelor; Ticlopidine - administration & dosage; Ticlopidine - analogs & derivatives; Ticlopidine - pharmacokinetics; Young Adult
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep31838

Ticagrelor has a greater antiplatelet efficacy than clopidogrel but may be accompanied by an increased risk of bleeding. This study evaluated the antiplatelet effect and pharmacokinetic profile of low-dose ticagrelor in healthy Chinese volunteers. Thirty healthy subjects were randomized to receive standard-dose ticagrelor (180-mg loading dose, 90-mg twice daily [bid] [n = 10]), low-dose ticagrelor (90-mg loading dose, 45-mg bid [n = 10]), or clopidogrel (600-mg loading dose, 75-mg once daily [n = 10]). Platelet reactivity was assessed by using the VerifyNow P2Y12 assay at baseline and 0.5, 1, 2, 4, 8, 24, 48 and 72 hours post-dosing. The ticagrelor and AR-C124910XX concentrations were measured for pharmacokinetic analysis. The percentage inhibition of P2Y12 reaction units was higher in the low-dose and standard-dose ticagrelor group than in the clopidogrel group at 0.5, 1, 2, 4, 8 and 48 hours post-dosing ( P  < 0.05 for all), but did not differ significantly between the two ticagrelor doses at any time-point ( P  > 0.05). The plasma ticagrelor and ARC124910XX concentrations were approximately 2-fold higher with standard-dose versus low-dose ticagrelor. No serious adverse events were reported. In conclusion, low-dose ticagrelor achieved faster and higher inhibition of platelet functions in healthy Chinese subjects than did clopidogrel, with an antiplatelet efficacy similar to that of standard-dose ticagrelor.