COMPASS: Clinical Trial - Post Revascularization & Chronic PAD

XARELTO^® VASCULAR DOSE*: COMPASS CLINICAL TRIAL IN PATIENTS WITH CAD AND/OR PAD^1-3

Supported by robust evidence in ~27,395 patients^1,2

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.

COMPASS DEFINITIONS OF CAD AND PAD³

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

COMPASS BASELINE CHARACTERISTICS¹

COMPASS STUDY INCLUSION OR EXCLUSION CRITERIA³

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

COMPASS STUDY OUTCOMES¹

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.