Low-dose of Ticagrelor and Standard-dose Clopidogrel on Platelet Effects in Chinese Patients With Stable CAD.
Low-dose of Ticagrelor and Standard-dose Clopidogrel on Platelet Effects in Chinese Patients With Stable CAD.
Ticagrelor has been demonstrated to provide a more rapid and more powerful inhibition of
 platelet aggregation compared with clopidogrel in coronary artery disease (CAD) patients.
 However, current guidelines recommend ticagrelor 90 mg twice daily might not be suitable for
 patients of Chinese. Therefore, the investigators performed this study to observe the
 efficacy of 60-mg ticagrelor in comparison to 75-mg clopidogrel in Chinese patients with
 stable CAD.
Dual antiplatelet therapy with aspirin and a P2Y12 receptor antagonist is the established
 standard of care in ACS patients. Although a popular P2Y12 receptor inhibitor, clopidogrel is
 not the most potent antiplatelet agent due to its metabolic activation. Metabolic activation
 of clopidogrel depends on multiple cytochrome P450 (CYP) enzymes, including CYP2C19, which
 can delay the onset of its activity; in addition, some populations carry a reduced-function
 allele of the CYP2C19 gene. Notably, poor drug metabolism of clopidogrel is more common in
 Asian populations compared with other international regions, due to the prevalence of CYP2C19
 reduced-function alleles in these patients. A recent study indicated that Asians might have
 different adverse event profiles (thrombophilia and bleeding) and "therapeutic window"
 compared with white subjects, suggesting that regional differences may influence the altered
 response of clopidogrel to the onset of thrombotic events.

 Ticagrelor is an orally administered, reversibly-binding, direct-acting P2Y12 receptor
 antagonist used clinically for the prevention of atherothrombotic events in patients with
 ACS. Guidelines give a recommendation on the use of dual antiplatelet therapy (DAPT) support
 ticagrelor 90 mg twice daily over clopidogrel 75 mg daily in addition to aspirin in ACS
 patients with or without ST-segment elevation. Increasing evidence indicated that Asian
 patients showed higher active metabolite exposure rates and stronger pharmacodynamic
 responses than their Caucasian subjects when treated with the same oral doses of prasugrel
 .In Korea and Japan, it has been reported that low doses of ticagrelor might have a more
 potent inhibition of platelet aggregation (IPA) than clopidogrel in healthy subjects and
 patients with stable coronary artery disease, respectively .In our previous study, the
 investigators found that half-dose ticagrelor produced similar inhibitory effects on platelet
 aggregation as standard-dose ticagrelor and exerted significantly stronger effects than
 clopidogrel in patients with ACS and one-quarter standard-dose ticagrelor provided greater
 degree of platelet inhibition than clopidogrel in patients with stable CAD. Furthermore,
 standard-dose ticagrelor (180mg loading dose [LD], then 90mg twice daily) has a significant
 increase in the risk of bleeding and incidence rate of dyspnea, and that higher
 discontinuation rates due to adverse effects compared to clopidogrel. A recent study
 demonstrated that maximum plasma concentration and area under the plasma concentration-time
 curve of ticagrelor (90 mg twice daily) and its active metabolite (AR-C124910XX) tended to be
 approximately 40% higher in healthy Chinese volunteers compared with Caucasian subjects.
 Notably, poor drug metabolism of clopidogrel is more common in Asian populations compared
 with other international regions, due to the prevalence of CYP2C19 reduced-function alleles.
 The data suggested that a low dose of ticagrelor might be more appropriate for Chinese
 patients.

 The objectives of this study were to evaluate the effects of ticagrelor (60.0mg daily) in
 comparison to clopidogrel (75mg daily) on platelet reactivity in Chinese patients with stable
 CAD.
Inclusion Criteria:

 -  Patients were eligible to participate if they were aged ≥18 years and ≤ 75 Years

 -  Subjects had documented stable CAD (defned as stable angina pectoris and objective
 evidence of CAD, a previous MI, or previous revascularization with percutaneous
 coronary intervention or coronary artery bypass grafting)

 -  Women were required to be postmenopausal or surgically sterile

 -  Patients who were taking clopidogrel or ticagrelor were required to discontinue these
 agents at least 14 days before randomization

 Exclusion Criteria:

 -  Acute coronary syndrome (ACS)

 -  planned use of glycoprotein IIb/IIIa receptor inhibitors, adenosine diphosphate (ADP)
 receptor antagonists other than the study medication, or anticoagulant therapy during
 the study period

 -  platelet count <10*10^4/ul

 -  creatinine clearance rate < 30ml/min

 -  diagnosed as respiratory or circulatory instability (cardiac shock, severe congestive
 heart failure NYHA II-IV or left ventricular ejection fraction < 40%)

 -  a history of bleeding tendency

 -  allergy to aspirin, ticagrelor or clopidogrel

 -  diabetes patients