Low-dose rivaroxaban failed in advanced kidney disease, and raised bleeding

Low-dose rivaroxaban, a blood thinner that lowers cardiovascular events in people with stable coronary or peripheral artery disease, did not do the same in patients with advanced kidney disease — and it caused more major bleeding [s1]. The TRACK trial, an international randomised study, was stopped early for lack of efficacy, and its published results show a blood thinner failing to earn its keep in exactly the high-risk group that had been the obvious next place to try it [s1].

Why the question mattered

People with advanced chronic kidney disease (CKD) have a high burden of cardiovascular disease — roughly 10% to 15% suffer a fatal or non-fatal cardiovascular event each year — yet they are routinely excluded from the trials that establish antithrombotic drugs, so the effect of those drugs in this group was genuinely unknown [s1]. Rivaroxaban at a low, 2.5-mg twice-daily dose had reduced events in other high-risk populations, which made it a reasonable candidate to test here. The trial was coordinated by the George Institute for Global Health; its registry entry lists Bayer, the company that makes rivaroxaban, among the collaborators, so the drug's manufacturer was involved in a trial of its own product — a tie readers should weigh even when the result is negative [s2].

What the trial tested

TRACK was a randomised, double-blind, placebo-controlled trial run at 90 centres in 12 countries [s1]. Eligible participants were adults with CKD stage 4 or 5, including those dependent on dialysis, who also had a history of coronary artery disease, non-haemorrhagic non-lacunar stroke, peripheral artery disease or diabetes, or were 65 years or older [s1]. They were assigned in equal numbers to rivaroxaban 2.5 mg twice daily or placebo [s1]. The primary outcome was a composite of cardiovascular death, non-fatal myocardial infarction, stroke or a peripheral-artery-disease event; the primary safety outcome was major bleeding [s1]. Enrolment ran from January 2021, and the trial was stopped on 7 August 2025 for lack of efficacy, with final follow-up on 30 October 2025 [s1].

What it found

Of 1,458 randomised patients — mean age 63.2 years, 432 (29.6%) female — 1,360 (93.3%) completed follow-up [s1]. Over a median of 1.7 years, the primary cardiovascular outcome occurred in 164 patients (22.6%) on rivaroxaban and 151 (20.7%) on placebo, or 13.0 versus 11.8 events per 100 person-years — a hazard ratio of 1.09 (95% confidence interval 0.87 to 1.36; P = .46) [s1]. That point estimate sits slightly on the wrong side of 1, and the interval spans no effect in either direction; there was no signal of benefit [s1].

The safety side was not neutral. Major bleeding occurred in 64 patients (8.8%) on rivaroxaban and 44 (6.0%) on placebo — 5.1 versus 3.4 events per 100 person-years, a hazard ratio of 1.51 (95% CI 1.02 to 2.22; P = .04) [s1]. In other words, the drug delivered no reduction in the events it was meant to prevent while raising the rate of serious bleeding by about half [s1].

How to read it

The decision to stop for futility is itself informative: an independent monitoring process concluded the trial could not show the benefit it was designed to find, and continuing would expose participants to bleeding risk for no expected gain [s1]. The clean interpretation is that the event-lowering seen with low-dose rivaroxaban in other populations does not transfer to advanced kidney disease, where bleeding risk is high and the balance tips the wrong way [s1].

The limits are worth naming. A trial stopped early has fewer events than planned, which widens the confidence intervals and makes it harder to exclude a small benefit — but the direction of the primary estimate offers no encouragement, and the bleeding result is statistically significant [s1]. The finding applies to this specific low dose in this specific, very high-risk group; it does not speak to anticoagulation given for a distinct indication such as atrial fibrillation, where the reason to treat is different [s1].

What to watch

The practical question is whether the persistent temptation to extend proven cardiovascular therapies into CKD without dedicated trials now meets more resistance, given a well-run study that tested the idea directly and found harm without benefit [s1]. This article describes research and is not medical advice; anticoagulation decisions in kidney disease are made by treating clinicians.