Benefits of dual COMPASS regimen also seen in patients with moderate renal dysfunction
Rivaroxaban Plus Aspirin in Patients With Vascular Disease and Renal Dysfunction - From the COMPASS Trial
Introduction and methods
Chronic kidney disease (CKD) increases the risk of thromboembolism and bleeding, but anticoagulation therapy also increases bleeding risk in the presence of renal dysfunction [1-4]. Moreover, higher age and the prevalent comorbidities that are associated with vascular disease also negatively impact bleeding risk and adverse vascular outcomes. The extent of renal excretion of non-vitamin K antagonist oral anticoagulants varies, ranging from 25% to 80% of drug being excreted unchanged in the urine [5-7]. Thus, renal dysfunction may alter the risk-benefit balance for antithrombotic combinations.
The COMPASS study demonstrated that rivaroxaban 2.5 mg bd plus aspirin, compared with aspirin alone, reduced CV outcomes and increased major bleeding in patients with stable atherosclerotic vascular disease [8-10]. Rivaroxaban 5 mg twice daily on the other hand, did not reduce CV outcomes and was associated with higher bleeding risk .
This analysis assessed the safety and efficacy of low-dose anticoagulation with rivaroxaban plus aspirin (the dual pathway COMPASS regimen), compared with aspirin alone, in patients who are in sinus rhythm but at increased vascular risk, with or without moderate renal dysfunction. Patients in the COMPASS trial had chronic stable CAD and/or peripheral artery disease. 21.111 patients in the COMPASS population had GFR ≥60 mL/min at baseline and 6.275 had GFR <60 mL/min.
- The primary efficacy outcome of CV death, MI or stroke, was more frequent in those with renal dysfunction than in those without, and the frequency was inversely related to eGFR.
- Risk reductions with rivaroxaban plus aspirin were consistent in those with GFR ≥60 mL/min (3.5% vs. 4.5% with aspirin alone, HR: 0.76, 95%CI: 0.64-0.90) and in those with GFR <60 mL/min (6.4% vs. 8.4%, 95%CI: 0.75, 0.60-0.94).
- Also in those with more severe renal dysfunction (GFR <30 mL/min, n=243), a consistent, but non-significant risk reduction was seen (HR: 0.73, 95%CI: 0.28-1.91).
- Strokes of any cause were reduced with the dual regime in those with normal renal function (0.9% vs. 1.3%, HR: 0.67, 95%CI: 0.48-0.92) and with GFR <60 mL/min (1.0% vs. 2.3%, HR: 0.42, 95%CI: 0.25-0.70).
- CV death was lower in the COMPASS regimen group than in those treated with aspirin alone, both in those with GFR ≥60 mL/min (1.3% vs. 1.7%, HR: 0.73, 95%CI: 0.56-0.96) and in those with GFR <60 mL/min (3.5% vs. 3.9%, HR: 0.88, 95%CI: 0.64-1.20).
- No statistically significant interactions of the treatment effect on various efficacy and safety outcomes and renal function status were seen. When GFR was used on a continuous scale, a consistent benefit of the combination therapy was seen across the GFR range.
- Major bleeding occurred more often in those randomized to the COMPASS regime than in those on aspirin alone in those with GFR ≥60 mL/min (2.9% vs. 1.6%, HR: 1.81, 95%CI 1.44-2.28) and in those with GFR <60 mL/min (3.9% vs. 2.7%, HR: 1.47, 95%CI: 1.05-2.07).
- Net clinical benefit with the dual treatment regimen compared with aspirin alone, based on CV death, stroke, MI, fatal bleeding or symptomatic bleeding into critical organ, was consistent in those with GFR ≥60 mL/min (HR: 0.81, 95%CI: 0.69-0.94) and <60 mL/min (HR: 0.79, 95%CI: 0.64-0.98).
This analysis of COMPASS suggests that for both efficacy and safety, the relative treatment effects of the dual-pathway COMPASS regimen, consisting of rivaroxaban 2.5mg bd and aspirin, compared with aspirin alone, are consistent in those with preserved and moderately impaired renal function. A cut-off of GFR of 60 mL/min was used. Relatively few patients included in the COMPASS trial had GFR <30 mL/min, and by design, all had GFR >15 mL/min at baseline.