Connolly SJ, et al. - The purpose of this randomised, double-blind trial was to gauge the effect of rivaroxaban with or without aspirin, in patients with stable coronary artery disease. The addition of rivaroxaban to aspirin resulted in a lowering of the major vascular events. However, it increased major bleeding. No substantial rise was noted in the intracranial bleeding or other critical organ bleeding. The data illustrated a prominent net benefit in favour of rivaroxaban plus aspirin, wherein, the deaths were reduced by 23%. Hence, the addition of rivaroxaban to aspirin exhibited the ability to markedly reduce morbidity and mortality from coronary artery disease worldwide.

Methods

• This multicentre, double-blind, randomised, placebo-controlled, outpatient trial recruited patients with stable coronary artery disease or peripheral artery disease, from 602 hospitals, clinics, or community centres in 33 countries.
• It reported on patients with coronary artery disease.
• The inclusion criteria was patients with coronary artery disease presenting with a myocardial infarction in the past 20 years, multi-vessel coronary artery disease, history of stable or unstable angina, previous multi-vessel percutaneous coronary intervention, or previous multi-vessel coronary artery bypass graft surgery.
• Patients were randomly assigned (1:1:1) to receive rivaroxaban (2·5 mg orally twice a day) plus aspirin (100 mg once a day), rivaroxaban alone (5 mg orally twice a day), or aspirin alone (100 mg orally once a day), after a 30-day run in period.
• Randomisation was computer generated.
• Herein, each treatment group was double dummy, and the patients, investigators, and central study staff were masked to treatment allocation.
• The occurrence of myocardial infarction, stroke, or cardiovascular death were included as the primary outcome of the COMPASS trial.

Results

• A total of 27,395 patients were included in the COMPASS trial, between March 12, 2013, and May 10, 2016.
• Among the enrollees, 24,824 patients had stable coronary artery disease from 558 centres.
• The combination of rivaroxaban plus aspirin reduced the primary outcome more than aspirin alone (347 [4%] of 8,313 vs 460 [6%] of 8261; hazard ratio [HR] 0·74, 95% CI 0.65-0.86, p < 0.0001).
• Treatment with rivaroxaban alone, on the other hand, did not lead to a notable improvement in the primary outcome when compared with treatment with aspirin alone (411 [5%] of 8,250 vs 460 [6%] of 8,261; HR 0.89, 95% CI 0.78-1.02, p=0·094).
• The combination therapy of rivaroxaban plus aspirin treatment caused more major bleeds than treatment with aspirin alone (263 [3%] of 8,313 vs 158 [2%] of 8,261; HR 1.66, 95% CI 1.37-2.03, p < 0.0001).
• In the same way, more bleeds occurred in the rivaroxaban alone group than in the aspirin alone group (236 [3%] of 8,250 vs 158 [2%] of 8,261; HR 1.51, 95% CI 1.23-1.84, p < 0.0001).
• Gastrointestinal site was disclosed as the most common site of major bleeding, occurring in 130 [2%] patients who received combined rivaroxaban plus aspirin, in 84 [1%] patients who received rivaroxaban alone, and in 61 [1%] patients who received aspirin alone.
• It was reported that rivaroxaban plus aspirin reduced mortality than with aspirin alone (262 [3%] of 8,313 vs 339 [4%] of 8,261; HR 0.77, 95% CI 0.65-0.90, p=0.0012).