- TRACK was the first dedicated placebo-controlled trial to test an anticoagulant for protection from hard cardiovascular outcomes in patients with advanced CKD at high cardiovascular risk.
- In this population, historically excluded from landmark studies, low-dose rivaroxaban did not reduce the risk of a composite cardiovascular outcome and, in fact, increased major bleeding.
- Results are a departure from low-dose rivaroxaban’s benefit in broader populations, including patients with mild to moderate CKD.
An established blood thinner regimen failed to extend its cardioprotective benefits to patients with advanced chronic kidney disease (CKD), according to the international TRACK trial.
In this placebo-controlled study of patients with advanced CKD and cardiovascular risk factors and/or cardiovascular disease, low-dose rivaroxaban (Xarelto) was no help for reducing the composite of cardiovascular death, nonfatal myocardial infarction, stroke, or peripheral artery disease events during a median 1.7 years (22.6% vs 20.7% with placebo; HR 1.09, 95% CI 0.87-1.36).
What’s more, the primary safety outcome, major bleeding, put rivaroxaban users at a significant disadvantage (8.8% vs 6.0%; HR 1.51, 95% CI 1.02-2.22), reported study investigators led by Sunil Badve, PhD, of the University of New South Wales Sydney in Australia.
TRACK was published in JAMA and presented at the European Renal Association Congress.
Of note, the trial had been designed to enroll 1,900 people over 3 years. It started during the COVID-19 pandemic and was ultimately stopped early — with fewer than 1,500 patients randomized in August 2025 — for lack of efficacy upon interim analysis.
Another major caveat was the 28.2% rate of study drug discontinuation.
“This trial underscores the need for dedicated cardiovascular outcome trials in people with advanced CKD,” wrote Badve and colleagues.
Indeed, due to their known risk of bleeding, people with advanced CKD had been excluded from COMPASS and VOYAGER PAD. These were two major trials that reported reduced cardiovascular event and thrombotic vascular event rates when low-dose rivaroxaban was added to aspirin in patients with established coronary and peripheral artery disease, respectively, the basis for the eventual FDA approval of these indications.
“Trials conducted in broader populations, including patients with mild to moderate CKD, have suggested that low-dose rivaroxaban may confer cardiovascular protection. However, extrapolating these findings to advanced CKD is problematic given the distinct biology of uremia and other CKD-specific mechanisms in advanced CKD that heighten cardiovascular risk and increase susceptibility to bleeding,” explained Nisha Bansal, MD, of the University of Washington in Seattle, and Wolfgang Winkelmayer, MD, of Baylor College of Medicine in Houston, in an accompanying editorial.
Importantly, in TRACK, 42.1% of deaths in the advanced CKD population were due to sudden cardiac death — throwing into question the hypothesis that anticoagulation would be helpful in the first place.
“This observation calls for a strategic pivot in the design of future trials for cardiovascular disease in this population. Future investigations should more directly address the metabolic, inflammatory, and electrophysiological pathways that predominate in advanced CKD,” according to Bansal and Winkelmayer.
Even so, they wrote, the door “certainly” should not be closed on anticoagulation for cardiovascular protection in advanced CKD. Important questions remain regarding which patients are most likely to benefit (perhaps those with established cardiovascular disease) and whether alternative oral anticoagulation strategies may prove more effective or safer in selected CKD populations.
In the meantime, the unmet need is clear: cardiovascular disease continues to have a disproportionate burden in people with advanced CKD, accounting for nearly half their deaths.
The randomized double-blind trial TRACK was conducted in 12 countries on several continents.
Investigators sought to enroll both adults with CKD stage 4 or 5 not receiving kidney replacement therapy and those with dialysis-dependent kidney failure; eligible adults also had an increased risk of cardiovascular events based on a history of coronary artery disease, nonhemorrhagic and nonlacunar stroke, peripheral artery disease, diabetes, or age 65 years and older.
Exclusion criteria included mechanical or prosthetic heart valves (other than bioprosthetic valves), an indication for or contraindication to anticoagulant therapy, and high bleeding risk, among others.
Out of 5,979 people screened, there were 1,458 individuals randomized 1:1 to receive rivaroxaban 2.5 mg twice daily or placebo for the trial.
The cohort had a mean age of 63.2 years and was 29.6% women. They were roughly split between dialysis- and nondialysis-dependent groups. Over three-quarters had diabetes, almost half were at least 65, and nearly one in five had coronary artery disease.
Out of the whole cohort, 93.3% completed follow-up.
Badve and colleagues reported that low-dose rivaroxaban did not reduce all-cause mortality (25.6% vs 23.0%; HR 1.14, 95% CI 0.92-1.40), a key secondary outcome.
