This is a phase IV, prospective biomarker study that will be conducted at Sinai Hospital of Baltimore. After screening for patients who were treated with aspirin, thirty patients will be treated with 81 mg enteric coated (EC) aspirin for 7 days in the "lead-in" period and then will be randomly treated with EC aspirin (81mg qd) or EC aspirin (81mg qd) plus rivaroxaban (2.5 mg bid) for 12 weeks. Platelet aggregation, soluble markers of platelet activation and inflammation, thrombin generation kinetics and tissue factor (TF)-induced platelet-fibrin clot strength will be assessed at baseline (after 7 days of treatment with 81 mg EC aspirin), and 4 and 12 weeks after randomization of the study drug administration.

Inclusion Criteria: to qualify, all subjects must meet have CAD and PAD as according to criteria specified below:

• Subjects meeting criteria for CAD$ must have one or more of the following:
• Myocardial infarction within the past 20 years, or
• Multivessel coronary disease* with symptoms or with history of stable or unstable angina, or
• Multivessel percutaneous coronary intervention, or
• Multivessel CABG surgery (* Refers to stenosis of ≥ 50% in 2 or more coronary arteries, confirmed using invasive coronary angiography, or noninvasive imaging or stress studies (eg, exercise or pharmacologic) suggestive of significant ischemia in 2 ≥ coronary territories; or in 1 coronary territory if at least 1 other territory has been revascularized.)

$Subjects with the qualifying criteria of CAD must also met at least one of the following criteria:

• Age > 65 years, or

• Age <65 years and documented atherosclerosis or revascularization involving at least 2 vascular beds+, or at least 2 additional cardiovascular risk factors:

  1. Current smoker (within 1 year of randomization)

  2. Diabetes mellitus

  3. Renal dysfunction with estimated glomerular filtration rate of <60 ml/min

  4. Heart failure

  5. Non-lacunar ischemic stroke > 1 month ago

     • Because CAD involves disease in the coronary vasculature, only one additional vascular bed is required: e.g. the aorta and arterial supply to the brain, gastro-intestinal tract, lower limbs, upper limbs, or kidneys.

       • Subjects meeting criteria for PAD must have one or more of the following

• Previous aorto-femoral bypass surgery, limb bypass surgery, or percutaneous transluminal angioplasty revascularization of the iliac, or infrainguinal arteries, or

• Previous limb or foot amputation for arterial vascular disease (i.e., excludes trauma), or

• History of intermittent claudication and one of the following

  • An ankle/arm blood pressure (BP) ratio < 0.90,

  • Significant peripheral artery or venous stenosis of ≥50% documented by angiography or by duplex ultrasound

  • Previous carotid revascularization or asymptomatic carotid artery stenosis ≥ 50% as diagnosed using duplex ultrasound or angiography.

    • Subject may be of either sex and of any race, and must be >18 years of age.
    • Subject agrees to not participate in any other investigational or invasive clinical study for a period of 4 months during the study period
    • The subject is able to read and has signed and dated the informed consent document including authorization permitting release of personal health information approved by the investigator's Institutional Review Board (IRB).

Exclusion Criteria: Subjects will be excluded from entry if ANY of the criteria listed below are met:

• High risk of bleeding
• Stroke within 1 month or any history of hemorrhagic or lacunar stroke
• Severe heart failure with known ejection fraction <30% or New York Heart Association (NYHA) class III or IV symptoms
• Estimated glomerular filtration rate (eGFR)<15 mL/min
• Need for dual antiplatelet therapy, other non-aspirin antiplatelet therapy, or oral anticoagulant therapy
• Known non-cardiovascular disease that is associated with poor prognosis (e.g., metastatic cancer) or that increases the risk of an adverse reaction to study interventions.
• History of hypersensitivity or known contraindication for rivaroxaban, aspirin, or its excipients. Systemic treatment with strong inhibitors of both CYP 3A4 and p-glycoprotein (P-gp) (e.g., systemic azole antimycotics, such as ketoconazole, and human immunodeficiency virus [HIV]-protease inhibitors, such as ritonavir), or strong inducers of CYP 3A4, i.e. rifampicin, rifabutin, phenobarbital, phenytoin, and carbamazepine.
• Participation in any investigational study within the last 60 days.
• Active liver disease or hepatic dysfunction, defined as AST or ALT >3 x ULN as determined by laboratory test results drawn at or available during screening.
• Recipient of any major organ transplant (e.g., lung, liver, heart, bone marrow, renal).
• Subjects with prosthetic heart valves.
• Known major active infection or major hematologic, renal, metabolic, gastrointestinal, or endocrine dysfunction in the judgment of the investigator.
• Malignancy (except non-melanoma skin cancers, cervical in situ carcinoma, breast ductal carcinoma in situ, or stage 1 prostate carcinoma) within the last 5 years.
• Subject is pregnant or breast feeding, or planning to become pregnant or to breastfeed during receipt of investigational products and within 15 weeks after the end of study treatment.
• Female subject who is unwilling to use at least 2 effective birth control methods for at least 1 month before screening and 15 weeks after the end of treatment with investigational products, unless the subject is sterilized or postmenopausal.
• Subject likely to not be available to complete all protocol-required study visits or procedures, to the best of the subject's and investigator's knowledge.
• History or evidence of any other clinically significant disorder, condition, or disease other than those outlined above that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion.