Pharmacodynamic Effects of Low-dose Rivaroxaban With Antiplatelet Therapies
Condition: Coronary Artery Disease; Peripheral Arterial Disease; Atrial Fibrillation
MeSH terms: Atrial Fibrillation; Coronary Artery Disease; Peripheral Arterial Disease; Peripheral Vascular Diseases
Intervention: Rivaroxaban 2.5 mg Tablet
Intervention description: PD assessments will be conducted at 3 time points: i) baseline (while on standard of care antiplatelet therapy), ii) 7-10 days after adjunctive treatment with low dose rivaroxaban, and iii) 7-10 days after dropping aspirin.
Intervention MeSH terms: Rivaroxaban
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: The proposed investigation will be a prospective PD (pharmacodynamic) study conducted in cohorts of patients with CAD, PAD, or atrial fibrillation
Masking: None (Open Label)
Enrollment: 86.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: aspirin; clopidogrel; ticagrelor; rivaroxaban; pharmacodynamic (PD)

Summary:

      Recent studies indicate that anti-factor-Xa inhibition with low-dose rivaroxaban may have a
      role in the reduction of ischemic recurrences in patients with atherosclerotic disease
      manifestations.

      To date there is very little data, and not conducted in human subjects, on the interplay
      between anti-Xa blockade with low-dose rivaroxaban and antiplatelet therapies, and in
      particular how this affects profiles of platelet reactivity and thrombin generation. Given
      the potential role for the use of low-dose rivaroxaban for the prevention of ischemic
      recurrences in patients with atherothrombotic disease manifestations, including coronary
      artery disease (CAD) and peripheral arterial disease (PAD), the study team proposes a
      prospective pharmacodynamic (PD) investigation assessing the impact of low-dose rivaroxaban
      when used in combination with antiplatelet treatment regimens commonly used in clinical
      practice.
    

Eligibility criteria:

        Inclusion criteria:

          -  Known CAD (defined as angiographic evidence of >50% coronary artery stenosis or prior
             coronary revascularization) or PAD (defined as a positive ankle brachial index (ABI)
             or prior revascularization)

          -  on treatment with either aspirin (81mg/qd), aspirin (81mg/qd) plus clopidogrel
             (75mg/qd), or aspirin (81mg/qd) plus ticagrelor (90mg/bid) for at least 3 months per
             standard of care OR

          -  Atrial fibrillation (paroxysmal, persistent or permanent) on treatment with
             rivaroxaban 20 mg qd (if creatinine clearance [CrCl] >50 mL/min) or 15 mg qd (if CrCl
             15 - 50 mL/min) per standard of care. Patients with concomitant CAD or PAD who are
             also taking antiplatelet medications are not eligible. However, if these are only on
             oral anticoagulation with rivaroxaban (and no antiplatelet therapy) the person will be
             eligible.

        Exclusion criteria:

          -  Active pathological bleeding, history of clinically significant bleeding events, or
             deemed at increased risk of bleeding.

          -  CrCL <20 mL/min

          -  Any clinical indication to be on triple antithrombotic therapy (DAPT plus an oral
             anticoagulant)

          -  An acute coronary event in the past 90 days

          -  Prior hemorrhagic stroke or intracranial hemorrhage

          -  Ischemic stroke/transient ischemic attack in the past 6 months

          -  Chronic use of nonsteroidal anti-inflammatory drugs

          -  On treatment with combined P-gp and strong CYP3A4 inhibitors (e.g., ketoconazole,
             itraconazole, lopinavir/ritonavir, ritonavir, indinavir/ritonavir, and conivaptan) or
             inducers (e.g., carbamazepine, phenytoin, rifampin, St. John's wort).

          -  Known moderate or severe hepatic impairment (Child-Pugh B and C)

          -  Prior hypersensitivity reaction to rivaroxaban

          -  On treatment with prasugrel in the past 10 days.

          -  Platelet count <80x106/mL

          -  Hemoglobin <10g/dL

          -  Hemodynamic instability

          -  Pregnant females [women of childbearing age must use reliable birth control (i.e. oral
             contraceptives) while participating in the study].