XARELTO® VASCULAR DOSE*: COMPASS CLINICAL TRIAL IN PATIENTS WITH CAD AND/OR PAD1-3

Supported by robust evidence in ~27,395 patients1,2

Trial Design

TRIAL DESIGN1

The COMPASS trial was a phase 3, multicenter, double-dummy, event-driven study of patients with a history of stable atherosclerotic vascular disease. Using a 1:1:1 randomization, patients received XARELTO® 2.5 mg twice daily plus aspirin 100 mg once daily (n=9152), rivaroxaban 5 mg twice daily (n=9117), or aspirin 100 mg once daily (n=9126).

Because the rivaroxaban 5 mg dose alone was not superior to aspirin alone, only the data concerning the XARELTO® 2.5 mg dose plus aspirin are discussed.

CAD 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

PAD 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 surgery (CABG)

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.

ACE = angiotensin-converting enzyme; ARB = angiotensin II receptor blocker; CABG = coronary artery bypass graft; CAD = coronary artery disease; CV = cardiovascular; CYP3A = cytochrome P450; eGFR = estimated glomerular filtration rate; ISTH = International Society on Thrombosis and Haemostasis; MI = myocardial infarction; NSAID = nonsteroidal anti-inflammatory drug; NYHA = New York Heart Association; PAD = peripheral artery disease; PPI = proton pump inhibitor.

*XARELTO® 2.5 mg twice daily plus aspirin 100 mg once daily.
Post-CABG patients were not included in the 30-day run-in.