Low-Dose Rivaroxaban in Advanced CKD: TRACK Trial Results

Key Takeaways

• Low-dose rivaroxaban was not associated with a lower primary cardiovascular composite in adults with advanced CKD, including those receiving dialysis.
• Major bleeding was more frequent with rivaroxaban than placebo, rising from 6.0% to 8.8% with a hazard ratio of 1.51.
• Net clinical benefit was not significantly different, subgroup and sensitivity analyses were broadly consistent, and the trial stopped early after interim review.

In adults with chronic kidney disease stage 4 or 5, including dialysis-dependent kidney failure, rivaroxaban 2.5 mg twice daily did not reduce the primary cardiovascular composite versus placebo in JAMA, with event rates of 22.6% and 20.7% and a hazard ratio of 1.09. This cardio-renal population had substantial baseline risk for both cardiovascular events and bleeding complications. Major bleeding was higher with rivaroxaban than with placebo. Overall, the trial did not show cardiovascular benefit in this population.

The TRACK trial was an investigator-initiated, randomized, double-blind, placebo-controlled study conducted at 90 centers in 12 countries and published in JAMA. Researchers randomized 1458 adults 1:1, with 727 assigned to rivaroxaban and 731 assigned to placebo after eligibility screening. Eligible participants had CKD stage 4 or 5, including 743 with nondialysis-dependent CKD and 715 with dialysis-dependent kidney failure; mean age was 63.2 years. Women made up 29.6% of the cohort. Enrollment ran from January 2021 through July 2025, and final follow-up was October 30, 2025. The primary outcome combined cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or a nonfatal peripheral artery disease event, with median follow-up of 1.7 and 1.8 years for efficacy and bleeding assessment.

Across follow-up, primary outcome rates were similar between groups. Major bleeding occurred in 8.8% of rivaroxaban-treated patients and 6.0% of placebo-treated patients, with a hazard ratio of 1.51, 95% CI 1.02-2.22, and P=.04. The prespecified net clinical benefit outcome occurred in 24.2% and 21.3%, respectively, with a hazard ratio of 1.14, 95% CI 0.92-1.41, and P=.25. Gastrointestinal bleeding was reported in 4.0% versus 2.3%, while intracranial bleeding occurred in 6 patients receiving rivaroxaban and 3 receiving placebo overall. The primary efficacy and net clinical benefit outcomes were similar between groups, while major bleeding was higher with rivaroxaban.

Prespecified subgroup analyses for the primary outcome were consistent across age, sex, country or region, aspirin use, diabetes, CKD stage, and smoking status. Major bleeding was higher among patients 65 years or older, with an interaction P=.03, in subgroup analysis. Competing-risk analysis was similar to the main result, with a subdistribution hazard ratio of 1.08, and the prespecified win ratio was 0.91 with P=.38.

After a prespecified interim review, the DSMB recommended stopping the trial, and the steering committee did so on August 7, 2025, citing concern for net harm and a low probability of demonstrating efficacy; the recommendation was not based on prespecified stopping rules. Investigators estimated 16% conditional power and noted that early stopping, inability to formally assess adherence because the COVID-19 pandemic prevented tablet counts, study-drug discontinuation, no minor bleeding data, no US participation, and few participants who identified as Black constrained interpretation.