CAD was defined as:

• Myocardial infarction within the past 20 years, or
• Multivessel coronary disease with symptoms or with a history of stable or unstable angina, or
• Multivessel percutaneous coronary intervention, or
• Multivessel coronary artery bypass graft (CABG) surgery

PAD was defined as:

• Previous aortofemoral 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, or
• History of intermittent claudication and 1 or more of the following:
  • Ankle/arm blood pressure ratio <0.9, or
  • Significant peripheral artery stenosis (≥50%) documented using angiography or duplex ultrasound, or
• Previous carotid revascularization or asymptomatic carotid artery stenosis (≥50%) as diagnosed using ultrasound or angiography

Inclusion criteria:

CAD or PAD plus at least one of the following:

• Age 65 years or older
• Age younger than 65 years and documented atherosclerosis or revascularization involving at least 2 vascular beds or at least 2 additional risk factors:
  • Current smoker (within 1 year of randomization)
  • Diabetes mellitus
  • Renal dysfunction with eGFR <60 mL/min
  • Heart failure
  • Non-lacunar ischemic stroke ≥1 month ago

Exclusion criteria:

• 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 NYHA class III or IV symptoms
• Estimated eGFR <15 mL/min
• Need for dual antiplatelet therapy, other nonaspirin therapy, or oral anticoagulant therapy
• Known noncardiovascular disease that is associated with poor prognosis (eg, metastatic cancer) or that increases the risk of an adverse reaction to study interventions
• History of hypersensitivity or known contraindication to XARELTO^®, aspirin, pantoprazole, or excipients, if applicable
• Systemic treatment with strong inhibitors or CYP3A as well a p-glycoprotein (eg, systemic azole antimycotics, such as ketoconazole, and HIV-protease inhibitors, such as ritonavir), or strong inducers of CYP3A (ie, rifampicin, rifabutin, phenobarbital, phenytoin, and carbamazepine)
• Any known hepatic disease associated with coagulopathy
• Subjects who are pregnant, breastfeeding, or of childbearing potential (sexually active and not practicing an effective method of birth control [eg, surgical sterilization, prescription oral contraceptives, contraceptive injection, intrauterine device, double-barrier method, contraceptive patch, or male partner sterilization])
• Known contraindication to any study-related procedures

Primary outcomes were a composite of cardiovascular death, myocardial infarction, and stroke. The principal safety outcome was a modification of the ISTH criteria for major bleeding and included fatal bleeding, symptomatic bleeding into a critical organ, bleeding into a surgical site requiring reoperation, and bleeding that led to hospitalization with or without an overnight stay.