Summary

• COMPASS (Cardiovascular OutcoMes for People Using Anticoagulation StrategieS) was a phase 3, event-driven, double-blind, randomized study designed to evaluate whether treatment with XARELTO 2.5 mg twice daily (BID) and aspirin 100 mg once daily (QD) or XARELTO 5 mg BID alone is more effective than aspirin 100 mg QD alone for prevention of myocardial infarction (MI), stroke, or cardiovascular (CV) death in patients with a history of stable atherosclerotic vascular disease (coronary artery disease [CAD] or peripheral artery disease [PAD]).¹
• There are no clinical studies that directly evaluated use of XARELTO for prophylaxis and/or treatment of venous thromboembolism (VTE) in patients with CAD or PAD.
• For reduction of risk of major CV events (CV death, MI, and stroke) in patients with chronic CAD or PAD, the recommended dose of XARELTO is 2.5 mg orally BID, with or without food, in combination with aspirin (75-100 mg) QD.²
• For treatment of deep vein thrombosis (DVT) and/or pulmonary embolism, the recommended dose of XARELTO is 15 mg orally BID with food for the first 21 days, followed by 20 mg orally QD with food for the remaining treatment. For prophylaxis of DVT following hip or knee replacement surgery, the recommended dose of XARELTO is 10 mg orally QD with or without food.²

CLINICAL STUDY

COMPASS

COMPASS was a phase 3, event-driven, double-blind, randomized study designed to evaluate whether treatment with XARELTO 2.5 mg BID and aspirin 100 mg QD or XARELTO 5 mg BID alone is more effective than aspirin 100 mg QD alone for prevention of MI, stroke, or CV death in 27,395 patients with a history of stable atherosclerotic vascular disease (CAD or PAD).¹

Study Design/Methods

• Primary efficacy outcome: the composite of MI, stroke, or CV death.
• Primary safety outcome (based on modified International Society on Thrombosis and Hemostasis criteria): major bleeding, including fatal bleeding, symptomatic bleeding into a critical organ, bleeding into a surgical site requiring reoperation, and bleeding leading to hospitalization (including presentation to an acute care facility without overnight stay).

Inclusion/Exclusion Criteria

• Key inclusion criteria included: PAD; CAD with ≥1 of the following: age ≥65 years or age <65 years and documented atherosclerosis or revascularization involving ≥2 vascular beds or ≥2 additional risk factors: current smoker (within 1 year of randomization), diabetes mellitus, renal dysfunction with estimated glomerular filtration rate (eGFR) <60 mL/min, heart failure (HF), or nonlacunar ischemic stroke ≥1 month ago.
• Key exclusion criteria included: stroke within 1 month or any history of hemorrhagic or lacunar stroke; severe HF with known ejection fraction <30% of New York Heart Association class III or IV symptoms; need for dual antiplatelet therapy, other nonaspirin antiplatelet therapy, or oral anticoagulant therapy; eGFR <15 mL/min; systemic treatment with strong inhibitors of both cytochrome P450 (CYP) 3A4 and P-glycoprotein or strong inducers of CYP3A4. Patients with atrial fibrillation (AF) requiring anticoagulation were also excluded.

Dosing Interventions

• Dosing interventions were as follows:
  • XARELTO 2.5 mg BID and aspirin 100 mg QD
  • XARELTO 5 mg BID and placebo QD
  • Placebo BID and aspirin 100 mg QD
• Patients who were not already receiving a proton pump inhibitor were randomized, using a partial factorial design, to receive pantoprazole 40 mg QD or placebo for prevention of upper gastrointestinal complications.
• Eligible participants (except those who underwent randomization 4 to 14 days after coronary artery bypass graft surgery) entered a run-in phase during which they received a XARELTO-matched placebo BID and aspirin at a dose of 100 mg QD.

Need for Anticoagulant Therapy During Study Period

• The following guidance is provided based on the COMPASS study protocol³:
  • Patients who developed a need for anticoagulant therapy (thromboprophylaxis in patients undergoing major orthopedic surgery, acute VTE, AF, mechanical aortic valve replacement) had to interrupt study XARELTO/XARELTO placebo. Study XARELTO/XARELTO placebo had to be restarted in patients who no longer had a need for nonstudy anticoagulant therapy (after completion of anticoagulant thromboprophylaxis or anticoagulant treatment for VTE). In those who developed a need for anticoagulant therapy, study aspirin/aspirin placebo would also possibly have to be interrupted, at the discretion of the investigator.

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, DERWENT^® (and/or other resources, including internal/external databases) was conducted on 23 October 2024.