Rivaroxaban should not be recommended for cardiovascular prevention in patients with advanced CKD

Low-dose rivaroxaban did not improve cardiovascular outcomes in patients with advanced chronic kidney disease (CKD) compared with placebo, but was associated with an increased risk of major bleeding events.

Prof. Sunil Badve (University of New South Wales, Australia) presented results from TRACK (NCT03969953), a phase 3, investigator-initiated, multicentre, randomised, double-blind, placebo-controlled, multinational trial that evaluated low-dose rivaroxaban (2.5 mg twice daily) versus placebo in patients with advanced CKD [1]. Patients were eligible if they had stage 4 or 5, including those receiving dialysis, and were at high cardiovascular risk. Patients with bleeding disorders or at high risk of bleeding were excluded. The primary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or a non-fatal peripheral artery disease event.

A total of 1,458 patients were randomised. However, the independent safety data monitoring committee recommended early termination of the trial because of “concerns about increased bleeding and a low probability of demonstrating efficacy,” said Prof. Badve. The primary outcome occurred in 20.7% of patients receiving placebo (11.8 events per 100 person-years) and in 22.6% of patients receiving rivaroxaban (13.0 events per 100 person-years; HR 1.09; 95% CI 0.87–1.36; P=0.46). Analysis of the individual components of the primary endpoint showed no benefit of rivaroxaban over placebo for any of the 4 outcomes. However, rivaroxaban significantly increased the incidence of major bleeding compared with placebo (5.1 vs 3.4 events per 100 patient-years; HR 1.51; 95% CI 1.02–2.22; P=0.04). The gastrointestinal tract was the most common site of major bleeding, and 6.3% of patients receiving low-dose rivaroxaban required hospitalisation due to bleeding compared with 4.7% of those receiving placebo.

“In patients with advanced CKD at high cardiovascular risk, low-dose rivaroxaban did not reduce the risk of the composite cardiovascular outcome,” concluded Prof. Badve. “Major bleeding events were significantly more frequent with low-dose rivaroxaban than with placebo.”

Badve S, et al. Low-dose rivaroxaban in patients with advanced kidney disease and high cardiovascular risk: an international randomised, placebo-controlled trial. ERA 2026, 3–6 June. Glasgow, Scotland.