What are the treatment recommendations based on the COMPAS (Cardiovascular Outcomes Microvascular or other Physiologic Assessment Study) trial for patients with cardiovascular diseases?

Treatment Recommendations Based on the COMPASS Trial

For patients with coronary artery disease (CAD) or peripheral artery disease (PAD), dual antithrombotic pathway inhibition (DAPI) with low-dose rivaroxaban (2.5 mg twice daily) plus low-dose aspirin (100 mg daily) is recommended to reduce cardiovascular events and mortality.

Understanding the COMPASS Trial

The COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial was a landmark study that randomized 27,395 patients with stable CAD or PAD to three treatment arms:

• Rivaroxaban 2.5 mg twice daily plus aspirin 100 mg daily
• Rivaroxaban 5 mg twice daily alone
• Aspirin 100 mg daily alone

The trial demonstrated that the combination of low-dose rivaroxaban plus aspirin:

• Reduced major adverse cardiovascular events (MACE) by 24% 1
• Reduced all-cause mortality by 18% 1
• Reduced stroke incidence by 42% 1
• Provided a 20% relative risk reduction in net clinical benefit 1

Patient Selection for DAPI Therapy

High-Risk Patients Who Benefit Most

The greatest absolute benefit from DAPI was observed in patients with:

1. Polyvascular disease (CAD plus PAD) 1
2. Heart failure 1
3. Chronic kidney disease (eGFR 15-59 mL/min/1.73 m²) 1
4. Type 2 diabetes mellitus 1

A CART (Classification and Regression Tree) analysis identified that patients with ≥2 vascular beds affected, history of heart failure, or diabetes derived the highest net clinical benefit from DAPI therapy 2.

Risk Stratification

The European Society of Cardiology provides a risk stratification approach for considering DAPI therapy 1:

High thrombotic risk (Class IIa recommendation):

• Complex CAD plus at least one risk enhancer:
  • Diabetes mellitus requiring medication
  • History of recurrent MI
  • Polyvascular disease
  • CKD with eGFR 15-59 mL/min/1.73 m²
  • Premature or accelerated CAD

Moderate thrombotic risk (Class IIb recommendation):

• Non-complex CAD plus at least one risk enhancer

Bleeding Risk Considerations

While DAPI therapy reduces cardiovascular events, it does increase bleeding risk:

• Major bleeding increased from 1.9% with aspirin alone to 3.1% with DAPI 1
• Bleeding was primarily gastrointestinal, with no significant increase in fatal or intracranial bleeding 1, 3
• Bleeding risk was higher in the first year of treatment 1

Important caveat: DAPI therapy should be avoided in patients with high bleeding risk, such as those with:

• Recent major bleeding
• Severe renal impairment (eGFR <15 mL/min/1.73 m²)
• Need for dual antiplatelet therapy or full-dose anticoagulation
• History of hemorrhagic or lacunar stroke

Implementation in Clinical Practice

Transitioning from DAPT to DAPI

For patients with recent acute coronary syndrome, the recommended approach is:

1. Complete 12 months of dual antiplatelet therapy (DAPT)
2. Assess risk of stent-related vs. systemic atherothrombotic risk factors
3. Consider switching to DAPI for long-term secondary prevention 1

Practical Algorithm for Patient Selection

1. Identify eligible patients: Those with stable CAD or PAD
2. Risk stratify: Assess for high-risk features (polyvascular disease, heart failure, diabetes, CKD)
3. Assess bleeding risk: Avoid in patients with high bleeding risk
4. Initiate therapy: Rivaroxaban 2.5 mg twice daily plus aspirin 100 mg daily

Real-World Applicability

External validation studies suggest that approximately 15% of patients undergoing coronary angiography would be eligible for COMPASS-based DAPI therapy 4. These eligible patients had up to 2.5-fold higher rates of cardiovascular events than non-eligible patients, highlighting the importance of identifying appropriate candidates for this therapy.

Monitoring Recommendations

• Regular assessment of bleeding risk
• No routine coagulation monitoring (PT/INR) required
• Closer monitoring during the first year when bleeding risk is highest

DAPI represents a significant advance in secondary prevention for patients with atherosclerotic vascular disease, with benefits that extend beyond traditional antiplatelet therapy alone.