Impact of CYP2C19 Genotype-guided Clopidogrel and Ticagrelor Treatment on Platelet Function Test and Metabolomics Profile
Condition: Coronary Artery Disease (CAD)
MeSH terms: Coronary Artery Disease; Myocardial Ischemia; Coronary Disease
Study type: Interventional
Phase: Phase 4

Summary: 
      Several studies have shown that pharmacodynamic (PD) response varies between patients treated
      with clopidogrel and that individuals with reduced response have an increased risk of
      recurrent ischemic events, particularly in patients undergoing percutaneous coronary
      intervention. This is due to several factors influencing the response to clopidogrel,
      including genetic variations of the cytochrome P450 (CYP) 2C19 enzyme. Loss of function (LOF)
      carriers of the CYP2C19 gene are associated with the decreased generation of the active
      metabolite clopidogrel and decreased platelet inhibition, which translates to an increased
      rate of adverse cardiovascular events, particularly in the setting of percutaneous coronary
      intervention (PCI). Thus, drug regulatory authorities have cautioned about the decreased
      efficacy of clopidogrel among individuals with CYP2C19 LOF carriers and suggested using
      alternative therapies to inhibit p2Y12. Ticagrelor is a new generation P2Y12 receptor
      inhibitor with greater efficacy for PD and reduced rates of ischemic events compared with
      clopidogrel and are not affected by the CYP2C19 LOF polymorphism. However, in clinical
      practice, the genotype-guided selection strategy for the oral P2Y12 inhibitor has been
      limited despite intensive research efforts. This is due to the interaction of cardiovascular
      risk factors and molecular and biochemical complications that lead to poor response to
      platelet inhibitor therapy, which impedes physicians' ability to prescribe a more effective
      and personalized antiplatelet therapy. Therefore, we must move away from traditional
      approaches and use integrated systems biology study designs and disciplines to bridge the gap
      between genotype, phenotype, disease manifestation and/or recurrence. Pharmacometabolomics is
      a rapidly developing field that takes advantage of a systems pharmacology approach to probe
      the molecular pathways involved in drug response variability to understand metabolic changes
      and identify novel biomarkers that can be used to predict response more comprehensively.
      Using profiles of changes in metabolites can help establish drug exposure fingerprints and
      clarify the determinants of drug response. This study aims to investigate the Impact of
      pharmacogenetics-guided clopidogrel and ticagrelor treatment on platelet function test and
      its association with metabolomics in Coronary Artery Disease (CAD) patients undergoing PCI in
      Malaysia
    


Intervention name(s): Clopidogrel; Ticagrelor
Intervention type(s): Drug; Drug
Intervention description(s): Comparison of platelet reactivity between clopidogrel and ticagrelor; Comparison of platelet reactivity between clopidogrel and ticagrelor
Other intervention name(s): Plavix; Brilinta
Intervention MeSH terms: Clopidogrel; Ticagrelor
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment