PAD: association of NOCA and aspirin is efficient despite a higher risk of bleeding

COMPASS

COMPASS study 

COMPASS PAD: Among 7,470 participants with peripheral arterial disease (PAD), 4,129 had symptomatic PAD, 1,919 had carotid disease, and 1,422 had coronary artery disease plus ankle-brachial index <0 .9.="" br="">

Major adverse cardiac events (MACE): 5.1% for rivaroxaban plus aspirin, 6.0% for rivaroxaban alone, vs. 6.9% for aspirin alone (p = 0.005 for rivaroxaban plus aspirin vs. aspirin alone; p = 0.19 for rivaroxaban alone vs. aspirin alone)
Major adverse limb events: 6.3% for rivaroxaban plus aspirin, 7.6% for rivaroxaban alone, vs. 9.0% for aspirin alone (p = 0.0003 for rivaroxaban plus aspirin vs. aspirin alone; p = 0.08 for rivaroxaban alone vs. aspirin alone)
Major bleeding: 3.1% for rivaroxaban plus aspirin, 3.2% for rivaroxaban alone, vs. 1.9% for aspirin alone (p = 0.009 for rivaroxaban plus aspirin vs. aspirin alone; p = 0.004 for rivaroxaban alone vs. aspirin alone)

http://www.acc.org/latest-in-cardiology/clinical-trials/2017/08/26/02/19/compass

Study Design
Randomized
Parallel
Blinded

Patients with stable atherosclerosis were randomized to rivaroxaban 2.5 mg twice daily plus aspirin (n = 9,152) vs. rivaroxaban alone (n = 9,117) vs. aspirin alone (n = 9,126).
Total number of enrollees: 27,395
Duration of follow-up: mean 23 months
Mean patient age: 68 years
Percentage female: 23%
Percentage with diabetes: 38%

Inclusion criteria:
Atherosclerosis in ≥2 vascular beds or two additional risk factors (current smoking, diabetes, renal insufficiency, heart failure, or nonlacunar ischemic stroke ≥1 month)

Exclusion criteria:
High bleeding risk
Recent stroke or previous hemorrhagic or lacunar stroke
Severe heart failure
Advanced kidney disease
Use of dual antiplatelet therapy or anticoagulation
Limited prognosis

Principal Findings:

The primary outcome, incidence of cardiovascular death, myocardial infarction, or stroke, occurred in 4.1% of the rivaroxaban plus aspirin group vs. 4.9% of the rivaroxaban alone group vs. 5.4% of the aspirin alone group (p < 0.001 for rivaroxaban plus aspirin vs. aspirin alone; p = 0.12 for rivaroxaban alone vs. aspirin alone). The primary efficacy outcome was the same in all tested subgroups.

Secondary outcomes:
All-cause mortality: 3.4% for rivaroxaban plus aspirin, 4.0% for rivaroxaban alone, vs. 4.1% for aspirin alone (p = 0.01 for rivaroxaban plus aspirin vs. aspirin alone; p = 0.67 for rivaroxaban alone vs. aspirin alone)
Stroke: 0.9% for rivaroxaban plus aspirin, 1.3% for rivaroxaban alone, vs. 1.6% for aspirin alone (p < 0.001 for rivaroxaban plus aspirin vs. aspirin alone; p = 0.12 for rivaroxaban alone vs. aspirin alone)
Major bleeding: 3.1% for rivaroxaban plus aspirin, 2.8% for rivaroxaban alone, vs. 1.9% for aspirin alone (p < 0.001 for rivaroxaban plus aspirin vs. aspirin alone, p < 0.001 for rivaroxaban alone vs. aspirin alone)