ReAssessment of Anti-Platelet Therapy Using an InDividualized Strategy Based on GENetic Evaluation
Condition: Stable Coronary Artery Disease; Acute Coronary Syndrome; Percutaneous Coronary Intervention
MeSH terms: Coronary Artery Disease; Acute Coronary Syndrome
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      The objective of the RAPID GENE study is to evaluate the feasibility, efficacy and safety of
      a pharmacogenomic approach to anti-platelet therapy following coronary artery stenting using
      a CYP2C19*2 point-of-care genetic test.
    

Detailed description: 
      Effective medical treatment following acute coronary syndromes and percutaneous coronary
      intervention (PCI) consists of dual anti-platelet therapy with aspirin and clopidogrel.
      Despite this treatment approach, a substantial portion of patients continue to experience an
      increased rate of subsequent adverse cardiovascular events including death, myocardial
      infarction, and stent thrombosis. This persistent vulnerability has been associated with
      inadequate platelet inhibition in response to clopidogrel administration, a phenomenon
      referred to as clopidogrel resistance. Although multiple variables have been implicated in
      clopidogrel resistance, mounting evidence suggests a crucial role for the loss-of-function
      CYP2C19*2 genetic variant. Presence of the *2 allele has been associated with a 1.5- to
      6-fold increased risk of cardiovascular death, myocardial infarction, and stent thrombosis
      following PCI in patients treated with clopidogrel. These findings, recently bolstered by a
      meta-analysis, led the American Food and Drug Administration to issue a boxed warning for
      clopidogrel stating that poor metabolizers may not receive the full benefit of the drug.
      Consequently, experts have begun to advocate for routine genotyping in the context of dual
      anti-platelet therapy following PCI. A personalized approach to dual anti-platelet therapy
      following PCI is feasible given the presence of treatment alternatives such as prasugrel that
      are capable of overcoming clopidogrel resistance. Selective administration of prasugrel to
      patients at increased risk of clopidogrel resistance has the potential to successfully
      minimize adverse ischemic events, while simultaneously minimizing associated bleeding events
      and health care costs. A prospective pharmacogenomic approach to anti-platelet therapy has
      been previously hampered by limited access and the time-delay associated with genetic
      testing. The development of a point-of-care CYP2C19*2 genetic test that requires minimal
      training to operate carries the potential to overcome these obstacles and may facilitate the
      incorporation of pharmacogenomic strategies into routine clinical practice.

      Patients receiving percutaneous coronary intervention in the context of non-ST elevation
      acute coronary syndromes and stable coronary artery disease will be randomized to either a
      rapid genotyping strategy or standard therapy. Patients in the Rapid Genotyping arm will be
      screened for the presence of the CYP2C19*2 allele using a point-of-care genetic test.
      Carriers of the *2 allele will receive prasugrel 10 mg daily for 1 week. Non-*2 carriers in
      the Rapid Genotyping arm and all patients in the Standard Therapy arm will receive
      clopidogrel 75 mg daily. At the end of the 1 week period, efficacy of the treatment
      strategies will be evaluated using VerifyNow platelet function testing.
    

Intervention name(s): Point-of-care genetic screening with subsequent prasugrel administration to CYP2C19*2 carriers
Intervention type(s): Genetic
Intervention description(s): Patients found to carry the CYP2C19*2 allele will receive prasugrel 10 mg daily for 1 week. Non-carriers will receive clopidogrel 75 mg daily.
Other intervention name(s): Prasugrel (Effient)
Intervention MeSH terms: Prasugrel Hydrochloride
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: CYP2C19*2; Pharmacogenomics; Clopidogrel; Prasugrel; Percutaneous Coronary Intervention