A Pharmacodynamic Study Comparing Prasugrel Versus Ticagrelor in Patients Undergoing PCI With CYP2C19 Loss-of-function:
Condition: Coronary Artery Disease
MeSH terms: Coronary Artery Disease; Myocardial Ischemia; Coronary Disease
Study type: Interventional
Phase: Phase 4

Summary: 
      Numerous studies have shown that pharmacodynamics (PD) response profiles vary among
      clopidogrel treated patients and that individuals with reduced response have an increased
      risk of recurrent ischemic events. There are multiple factors contributing to clopidogrel
      response variability, including genetic variations of the cytochrome P450 (CYP) 2C19 enzyme.
      In particular, loss-of-function (LOF) alleles of the CYP2C19 enzyme reduce transformation of
      clopidogrel pro-drug into its active metabolite. Thus, patients carrying LOF alleles have
      lower levels of clopidogrel's active metabolite as well as diminished platelet inhibition,
      which translates into an increased rate of adverse cardiovascular events, particularly in the
      setting of percutaneous coronary intervention (PCI). Prasugrel and ticagrelor are novel
      generation P2Y12 receptor inhibitors characterized by greater PD potency and reduced ischemic
      event rates compared with clopidogrel, and are not affected by CYP2C19 LOF polymorphisms.
      However, to date there are limited head-to-head PD comparisons between these two new P2Y12
      receptors blockers, and there are no studies assessing on how these agents behave among
      CYP2C19 LOF carriers. The aim of the present study is to compare the PD effects of prasugrel
      versus ticagrelor in patients undergoing PCI with CYP2C19 LOF alleles using the novel
      point-of-care genetic testing Spartan RX-CYP2C19 which permits accurate and rapid
      identification of CYP2C19 genetic status.
    

Detailed description: 
      Clopidogrel is the most broadly utilized platelet P2Y12 receptor inhibitor. However, numerous
      studies have shown that pharmacodynamics (PD) response profiles vary among clopidogrel
      treated patients and that individuals with reduced response have an increased risk of
      recurrent ischemic events. There are multiple factors contributing to clopidogrel response
      variability. Among these, genetic variations of the cytochrome P450 (CYP) 2C19 enzyme, a key
      contributor to clopidogrel metabolism, have been involved. In particular, loss-of-function
      (LOF) alleles of the CYP2C19 enzyme reduce transformation of clopidogrel pro-drug into its
      active metabolite. Thus, patients carrying LOF alleles have lower levels of clopidogrel's
      active metabolite as well as diminished platelet inhibition, which translates into an
      increased rate of adverse cardiovascular events, particularly in the setting of percutaneous
      coronary intervention (PCI). Because of these findings, drug regulating authorities have
      provided a boxed warning on the product label of clopidogrel on the potential for reduced
      efficacy of clopidogrel among CYP2C19 LOF carriers and suggested considering alternative
      antiplatelet therapies for these individuals. Prasugrel and ticagrelor are novel generation
      P2Y12 receptor inhibitors characterized by greater PD potency and reduced ischemic event
      rates compared with clopidogrel, and are not affected by CYP2C19 LOF polymorphisms. However,
      to date there are limited head-to-head PD comparisons between these two new P2Y12 receptors
      blockers, and there are no studies assessing on how these agents behave among CYP2C19 LOF
      carriers. Tailoring antiplatelet therapy according to results of genetic testing has been
      limited in real world clinical practice because of not having readily accessible results of
      individual's genetic makeup. The aim of the present study is to compare the PD effects of
      prasugrel versus ticagrelor in patients undergoing PCI with CYP2C19 LOF alleles using the
      novel point-of-care genetic testing Spartan RX-CYP2C19 which permits accurate and rapid
      identification of CYP2C19 genetic status.
    

Intervention name(s): Prasugrel; Ticagrelor
Intervention type(s): Drug; Drug
Intervention description(s): Comparison of platelet reactivity between prasugrel and ticagrelor; Comparison of platelet reactivity between prasugrel and ticagrelor
Other intervention name(s): Effient; Brilinta
Intervention MeSH terms: Ticagrelor; Prasugrel Hydrochloride
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Coronary Artery Disease; Percutaneous Coronary Intervention; Genetic Polymorphism; Pharmacodynamic