The Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial, previously reported, compared three antithrombotic regimens as secondary prevention in patients with stable cardiovascular disease (n=27,395): low-dose antiplatelet (aspirin 100mg daily), anticoagulation (rivaroxaban 5mg twice daily) and the combination of low-dose antiplatelet and low-dose anticoagulation (aspirin 100mg daily and rivaroxaban 2.5mg twice daily). The study was stopped prematurely after a mean follow-up of 23 months based on the efficacy of the combination treatment (primary composite outcome of cardiovascular death, stroke, or myocardial infarction occurred in 4.1% vs. 5.4% with aspirin alone; HR 0.76; 95% CI 0.66 to 0.86; P<0.001).
The current subgroup analysis included patients with peripheral artery disease (n=7,470; median treatment duration of 21 months), showing similar results to the overall study population for the primary outcome. Additionally the combination was found to reduce the risk of major adverse limb events including major amputation in this subgroup (1% vs 2%; HR 0.54 95% CI 0.35-0.82, p=0.0037). The rate of major bleeding (mainly gastrointestinal) was however increased (3% vs. 2% with aspirin alone; HR 1.61, 95% CI 1.12-2.31; p=0.0089).
The authors of a related comment notes that several unresolved issues remain:
• The role of rivaroxaban plus aspirin in patients with peripheral artery disease requiring dual antiplatelet therapy is unknown• The benefits of the use of rivaroxaban instead of, or in addition to, clopidogrel are uncertain• Risks of gastrointestinal bleeding may have been underestimated as a third of patients were on a proton-pump inhibitor (PPI) at baseline and the remaining two-thirds were randomised to a PPI or no PPI (the results of this part of the study are not yet available) • The study did not include asymptomatic patients diagnosed with peripheral artery disease via screening ankle–brachial index• Early stopping of the trial may have overestimated treatment effect and prevented a more robust analysis of the group receiving rivaroxaban alone
A separate subgroup analysis looking at patients with stable coronary artery disease has been published.