Low-dose of Ticagrelor and Standard-dose Clopidogrel on Platelet Effects in Chinese Patients With Stable CAD.
Condition: Platelet Reactivity
MeSH terms: Coronary Artery Disease
Study type: Interventional
Phase: Phase 4

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): low-dose ticagrelor; Clopidogrel
Intervention type(s): Drug; Drug
Intervention description(s): low-dose ticagrelor (60.0 mg once daily) for 7 days,followed by a 2-week washout period then a 7 days crossover phase of clopidogrel (75mg once daily).; clopidogrel (75mg once daily) for 7 days,followed by a 2-week washout period then a 7 days crossover phase of low-dose ticagrelor (60.0 mg once daily).
Intervention MeSH terms: Clopidogrel; Ticagrelor
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Ticagrelor; clopidogrel; coronary artery disease; platelet reactivity