Low-dose rivaroxaban fails in advanced kidney disease as TRACK trial is halted early for net harm

Patients with advanced kidney disease die of cardiovascular disease at extraordinary rates, yet they are routinely excluded from the trials that define cardiology practice. TRACK was built to fill that gap. Instead, it confirmed how poorly evidence from other populations travels into the kidney clinic.

The investigator-initiated, quadruple-blind trial (NCT03969953) randomized 1,458 adults with CKD stage 4-5 (eGFR 29 mL/min/1.73 m2 or lower) or dialysis-dependent kidney failure, roughly half of them on dialysis, to rivaroxaban (Xarelto) 2.5 mg twice daily or placebo. All carried elevated cardiovascular risk. Over a median 1.7 years, the primary composite of cardiovascular death, nonfatal MI, nonfatal stroke, or nonfatal peripheral artery disease event occurred in 164 rivaroxaban patients (22.6%) versus 151 on placebo (20.7%) — a hazard ratio of 1.09 (95% CI, 0.87-1.36; P=.46).

There was no signal of benefit on any major secondary endpoint, including all-cause mortality (HR 1.14; 95% CI, 0.92-1.40). The trial was stopped early after the data monitoring board, at a prespecified interim review, recommended termination on July 8, 2025, citing “concerns regarding net harm and a low probability of demonstrating efficacy”; the steering committee accepted that recommendation on August 7, 2025. The article is explicit that the decision was not based on prespecified stopping rules. It rested instead on a post hoc analysis estimating a conditional power of just 16% for an assumed hazard ratio of 0.78.

More bleeding, no payoff

The harm was clearer than any benefit. Major bleeding, the primary safety outcome, occurred in 64 rivaroxaban-treated patients (8.8%) versus 44 placebo-treated patients (6.0%) — HR 1.51 (95% CI, 1.02-2.22; P=.04).

“Clinical decisions regarding anticoagulation in people with advanced kidney disease should not be extrapolated from other cardiovascular populations,” the authors wrote.

One mechanistic clue: 42.1% of deaths were sudden cardiac deaths, which the authors note may not be atherothrombotic — and so may sit beyond any anticoagulant’s reach. A nominal reduction in venous thromboembolism (HR 0.29; 95% CI, 0.09-0.87) sat outside the trial’s multiplicity-controlled testing hierarchy and carries no valid P value (reported as “NA”). After a missed primary endpoint, it is an exploratory, hypothesis-generating observation, not an established effect, and does not rescue the primary result.