What are the findings of the COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial?

From the Guidelines

The COMPASS trial demonstrated that rivaroxaban 2.5 mg twice daily plus aspirin significantly reduced major adverse cardiovascular events compared to aspirin alone in patients with stable atherosclerotic vascular disease. The trial, which enrolled 27,395 patients with stable atherosclerotic vascular disease, tested three strategies: rivaroxaban 2.5 mg twice daily plus aspirin, rivaroxaban 5 mg twice daily, and aspirin alone 1. The results showed that the combination of rivaroxaban plus aspirin significantly lowered the risk of major adverse cardiovascular events (MACEs) compared to either aspirin alone or rivaroxaban alone. Some key points from the trial include:

• The risk of MACEs was significantly lower with the combination of rivaroxaban plus aspirin compared with either aspirin alone or rivaroxaban alone 1
• There was an associated increased risk of bleeding with rivaroxaban, although no significant excess in fatal bleeding was noted 1
• The ischemic benefits of rivaroxaban were consistent in the subgroup with diabetes mellitus, suggesting that low-dose anticoagulation added to antiplatelet therapy may be another option for secondary prevention in patients with T2DM and stable CAD 1 The findings of the COMPASS trial suggest that for patients with stable atherosclerotic disease, particularly those at high ischemic risk and low bleeding risk, adding low-dose rivaroxaban to aspirin provides meaningful cardiovascular protection, by targeting both platelet activation (with aspirin) and thrombin generation (with rivaroxaban), providing more comprehensive antithrombotic protection than either strategy alone 1.

From the FDA Drug Label

The evidence for the efficacy and safety of XARELTO for the reduction in the risk of stroke, myocardial infarction, or cardiovascular death in patients with coronary artery disease (CAD) or peripheral artery disease (PAD) was derived from the double-blind, placebo-controlled Cardiovascular Outco Mes for People using Anticoagulation Strategie S trial (COMPASS) [NCT10776424]. A total of 27,395 patients were evenly randomized to rivaroxaban 2.5 mg orally twice daily plus aspirin 100 mg once daily, rivaroxaban 5 mg orally twice daily alone, or aspirin 100 mg once daily alone. Relative to placebo, XARELTO reduced the rate of the primary composite outcome of stroke, myocardial infarction or cardiovascular death: HR 0.76 (95% CI: 0.66,0.86; p=0. 00004).

The findings of the COMPASS trial were that rivaroxaban 2.5 mg twice daily plus aspirin 100 mg once daily reduced the rate of stroke, myocardial infarction, or cardiovascular death by 24% compared to aspirin alone, with a hazard ratio of 0.76.

• The benefit was observed early and was consistent over the entire treatment period.
• A benefit-risk analysis showed that for every 10,000 patient-years of treatment, XARELTO would prevent 70 CV events and result in 12 additional life-threatening bleeds.
• The results were consistent across major subgroups 2.

From the Research

Key Findings of the COMPASS Trial

• The COMPASS trial demonstrated that the combination of low-dose rivaroxaban and aspirin reduced major vascular events in patients with stable vascular disease 3.
• The trial showed a 25% reduction in serious vascular event incidence, equivalent to 23 events prevented per 1,000 patients treated for 30 months, at the cost of a nonsignificant 34% increase in severe bleeding 3.
• Further risk stratification can identify higher-risk patients, including those with ≥2 vascular beds affected, history of heart failure, renal insufficiency, or diabetes 3.
• The net clinical benefit remains favorable for most patients treated with rivaroxaban and aspirin compared with aspirin 3.

Subgroup Analyses

• In patients with prior percutaneous coronary intervention (PCI), dual pathway inhibition with rivaroxaban and aspirin produced consistent reductions in major adverse cardiovascular events and mortality, but with increased major bleeding 4.
• The benefits of the dual pathway COMPASS regimen were preserved in patients with moderate renal dysfunction without evidence of an excess hazard of bleeding 5.
• In patients with diabetes mellitus, the combination of aspirin plus rivaroxaban provided a similar relative degree of benefit on coronary, cerebrovascular, and peripheral end points, with a 3-fold greater reduction in all-cause mortality 6.
• For vascular surgeons, the COMPASS trial suggests that intensification of antithrombotic therapy with low-dose rivaroxaban plus aspirin should be considered in low bleeding risk peripheral artery disease patients who are at increased risk for ischemic and/or limb events 7.

Patient Selection and Risk Stratification

• High-risk patients, as identified by the REACH score or CART analysis, may derive greater benefit from the combination of rivaroxaban and aspirin 3.
• Patients with renal dysfunction, diabetes mellitus, or prior PCI may also benefit from this combination therapy, although the risk of bleeding should be carefully considered 4, 5, 6.
• A practical approach for clinicians is to consider the individual patient's risk profile and incorporate COMPASS data into practice, taking into account the potential benefits and risks of combination antithrombotic therapy 7.