COMPASS: Rivaroxaban plus aspirin significantly reduces atherothrombotic events in stable CVD
Rivaroxaban in combination with aspirin significantly reduces cardiovascular (CV) death, stroke or MI vs aspirin alone in patients with stable cardiovascular disease (CVD), according to late-breaking results of the COMPASS trial presented at the European Society of Cardiology (ESC) Congress 2017 in Barcelona, Spain.
The COMPASS trial included 27,395 patients with stable coronary artery disease (CAD) or peripheral artery disease (PAD) recruited from 33 countries in North America, South America, Asia, Western Europe, Eastern Europe, South Africa and Australia. In patients randomized to receive rivaroxaban 2.5 mg twice daily in combination with aspirin 100 mg once daily (n=9,152), the primary composite endpoint of CV death, MI or stroke (ie, major adverse cardiovascular event [MACE]) was reduced by 24 percent compared with those who received aspirin 100 mg once daily (n=9,126) (4.1 vs 5.4 percent; p<0.0001). [N Engl J Med 2017, doi: 10.1056/NEJMoa1709118]
“The Kaplan-Meier curves for MACE separated very early and continued to diverge during follow-up,” reported co-principal investigator Dr John Eikelboom of McMaster University, Hamilton, Canada. “However, no significant difference in MACE was observed between patients receiving monotherapy with rivaroxaban 50 mg twice daily [n=9,117] and those receiving aspirin alone [4.9 vs 5.4 percent; hazard ratio (HR), 0.90; p=0.12].”
“Looking at individual components of the primary composite endpoint, rivaroxaban plus aspirin reduced the risk of CV death by 22 percent [1.7 vs 2.2 percent; p=0.02], the risk of stroke by 42 percent [0.9 vs 1.6 percent; p<0.0001], and the risk of MI by 14 percent [1.9 vs 2.2 percent; p=0.14] vs aspirin alone,” he continued.
In view of the clear superiority of the combination of rivaroxaban and aspirin over aspirin alone, the data and safety monitoring board recommended on 6 February 2017 – after a mean follow-up of 23 months – that the rivaroxaban and aspirin arms be discontinued. At that point, 99.8 percent of follow-up was completed ahead of the planned follow-up duration of 3–4 years.
In terms of secondary endpoints, the combination of rivaroxaban and aspirin reduced the risk of CAD mortality, ischaemic stroke, MI or acute limb ischaemia by 28 percent vs aspirin alone (p<0.0001). The risk of CV death, ischaemic stroke, MI or acute limb ischaemia was reduced by 26 percent (p<0.0001), while the risk of all-cause mortality was reduced by 18 percent (p=0.01 [prespecified threshold p=0.0025]).
“The addition of rivaroxaban to aspirin resulted in an increase in major bleeding vs aspirin alone [hazard ratio (HR), 1.70; p<0.0001], but no significant increase in fatal bleeding [HR, 1.49; p=0.32], intracranial haemorrhage [HR, 1.10; p=0.77] or bleeding in other critical organs [HR, 1.43; p=0.14] was observed,” said Eikelboom.
“The results clearly show a net clinical benefit with the combination of rivaroxaban and aspirin over aspirin alone [HR, 0.80; p=0.0005],” he concluded. “For every 1,000 patients treated for an average of 23 months, rivaroxaban plus aspirin could prevent 13 CV deaths, MIs or strokes, and seven all-cause deaths, at a cost of 12 major bleeds, most of which were readily treatable.”
“The results of COMPASS represent an important step in thrombocardiology. They should lead to changes in guidelines on the management of stable CAD,” commented discussant Dr Eugene Brauwald of Brigham and Women’s Hospital, Boston, Massachusetts, US.
“In the ATLAS ACS 2 – TIMI 51 trial, rivaroxaban in combination with dual antiplatelet therapy [DAPT] reduced the risk of MACE by 26 percent [p=0.02] and the risk of CV mortality by 34 percent [p=0.002] compared with DAPT alone,” said Brauwald. [N Engl J Med 2012;366:9-19] “The next step of research would be to compare rivaroxaban plus aspirin with DAPT and with rivaroxaban plus a P2Y12 inhibitor. It would also be logical to compare rivaroxaban plus a P2Y12 inhibitor with DAPT.”