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 coronary artery disease (n=24,824), 20% of whom had both coronary artery disease and peripheral artery disease. The overall results were similar to those seen in the overall study population for the primary outcome, and additionally the combination reduced all-cause mortality (3% vs 4% with aspirin; HR 0.77, 95% CI 0.65-0.90, p=0.0012). The combination (and also rivaroxaban alone) was however associated with more major bleeds than aspirin alone (3% vs 2%; HR 1.66, 95% CI 1.37-2.03, p<0.0001), most commonly gastrointestinal (2% vs 1%; HR 2.13, 95% CI 1.57–2.88, p<0.0001). This is noteworthy considering that around 70% of the patients were taking a proton pump inhibitor (PPI).
The authors of a related Comment note that the number needed to treat (NNT) to prevent one primary event was 71 for the combination of rivaroxaban and aspirin over aspirin alone, which is not particularly attractive when also considering bleeding risk. It may however be worth considering underlying risk. For example, a 25% relative reduction in the primary endpoint in those with a baseline risk of 20% during follow-up yields a NNT of 20.
A separate subgroup analysis looking at patients with stable peripheral artery disease has been published.