IMPORTANCE: Approximately 10% to 15% of patients with advanced chronic kidney disease (CKD) experience a fatal or nonfatal cardiovascular event annually. The effects of antithrombotic therapies on cardiovascular events in patients with advanced CKD are unknown.
OBJECTIVE: To determine whether low-dose rivaroxaban reduces rates of adverse cardiovascular events compared with placebo in patients with advanced CKD.
DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled trial conducted at 90 centers in 12 countries. Eligible participants were adults with CKD stage 4 or 5 and patients with dialysis-dependent kidney failure. Participants had a history of either coronary artery disease; nonhemorrhagic, nonlacunar stroke; peripheral artery disease; diabetes; or were 65 years or older. Enrollment occurred between January 2021 and July 2025. The trial was stopped early on August 7, 2025, for lack of efficacy. Final follow-up occurred on October 30, 2025. Statistical analyses were conducted in February and March 2026.
INTERVENTIONS: Patients were randomized 1:1 to receive rivaroxaban 2.5 mg twice daily or placebo.
MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, stroke, or a peripheral artery disease event. The primary safety outcome was major bleeding.
RESULTS: Of 1458 randomized patients (mean [SD] age, 63.2 [11.6] years, 432 [29.6%] female), 1360 (93.3%) completed follow-up. During a median follow-up of 1.7 years, the primary outcome occurred in 164 patients (22.6%) in the low-dose rivaroxaban group and 151 (20.7%) in the placebo group (13.0 vs 11.8 events per 100 person-years; hazard ratio, 1.09 [95% CI, 0.87-1.36]; P = .46). Major bleeding occurred in 64 patients (8.8%) receiving low-dose rivaroxaban and 44 (6.0%) receiving placebo (5.1 vs 3.4 events per 100 person-years; hazard ratio, 1.51 [95% CI, 1.02-2.22]; P = .04).
CONCLUSIONS AND RELEVANCE: In patients with advanced CKD at high cardiovascular risk, low-dose rivaroxaban did not reduce the risk of a composite cardiovascular outcome. Major bleeding rates were significantly higher in the low-dose rivaroxaban group compared with the placebo group.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03969953.
| Discipline Area | Score |
|---|---|
| Internal Medicine |  |
| Hemostasis and Thrombosis |  |
| Nephrology | |
I think this is an interesting trial to consider given the high prevalence of ASCVD in CKD patients. The best takeaway is a "less is more"/"do no harm" approach, although given no change in the primary outcome was seen and the increased bleeding risk.
Patients with CKD have a high cardiovascular risk. In this trial, low-dose rivaroxaban was tested against placebo to prevent cardiovascular events. Unfortunately, the trial had to be stopped early due to lack of efficacy. In addition, despite the low-dose bleeding risk being increased in the verum group. Thus, rivaroxaban in the tested dose is not effective in reducing cardiovascular risk in CKD patients and increases bleeding risk.
