Advanced CKD: Rivaroxaban Adds Bleeding, Not Benefit

No cardiovascular gain, with a bleeding penalty

The randomized TRACK trial directly tested an attractive but uncertain strategy: adding low-dose anticoagulation to reduce cardiovascular events in people with advanced chronic kidney disease. The intervention was rivaroxaban 2.5 mg twice daily, often called the vascular dose because it has been studied for atherosclerotic cardiovascular disease outside advanced CKD.

The trial’s two central findings point in the same clinical direction. Rivaroxaban failed to reduce cardiovascular events compared with the control strategy, while major bleeding increased. That combination matters more than either result alone. A preventive treatment must produce enough cardiovascular benefit to justify its harms; TRACK did not establish that trade-off in stage 4–5 CKD or dialysis-dependent kidney failure.

This is not simply a neutral efficacy result. If a treatment has no demonstrated cardiovascular advantage but causes more major bleeding, the relevant conclusion is that routine preventive use has an unfavorable evidence profile. That conclusion applies to the tested strategy and population; it should not be extrapolated to every reason a patient with CKD might receive anticoagulation.

Why TRACK was needed

Advanced CKD creates a difficult cardiovascular paradox. Patients face high rates of myocardial infarction, stroke, peripheral vascular events and cardiovascular death, yet they also have substantial bleeding vulnerability. Uremic platelet dysfunction, anemia, vascular-access procedures, gastrointestinal disease, concomitant antiplatelet treatment and frequent invasive care can all shift the balance toward harm.

Rivaroxaban also depends partly on renal elimination. Severe loss of kidney function can alter drug exposure, while dialysis does not make pharmacology or bleeding risk equivalent to that in patients with preserved kidney function. These considerations make advanced CKD more than a higher-risk version of the general cardiovascular population.

The rationale for TRACK came partly from earlier vascular-protection trials. In COMPASS, low-dose rivaroxaban combined with aspirin reduced major cardiovascular outcomes in stable atherosclerotic disease, but it also increased major bleeding. VOYAGER PAD similarly supported a low-dose rivaroxaban strategy after lower-extremity revascularization in a selected peripheral artery disease population. Those trials established that low-dose anticoagulation can improve vascular outcomes in particular settings; they did not establish a class-wide preventive benefit for stage 4–5 CKD or dialysis-dependent kidney failure.

TRACK therefore addressed an evidence gap rather than merely repeating a successful strategy in a sicker cohort. Its negative efficacy result shows why evidence from less severe kidney disease cannot be assumed to carry into kidney failure. Baseline event rates may be higher, but higher risk does not guarantee greater treatment benefit. The mechanisms behind cardiovascular events in advanced CKD—including arrhythmia, sudden death, calcific vascular disease, heart failure and nonatherothrombotic processes—may be less responsive to factor Xa inhibition.

How to interpret the randomized evidence

TRACK was a peer-reviewed randomized trial in people with advanced CKD, including stage 4–5 disease and dialysis-dependent kidney failure. It compared the addition of rivaroxaban 2.5 mg twice daily with a control strategy and assessed cardiovascular outcomes alongside major bleeding. Randomization strengthens the causal interpretation of the observed difference between strategies, assuming allocation and follow-up were maintained as reported.

The most important bedside point is the direction of both outcomes rather than a claim that the drug was merely “underpowered” for benefit. The trial did not demonstrate fewer cardiovascular events, and the safety outcome moved against rivaroxaban. An uncertain benefit cannot be used to cancel a demonstrated bleeding liability.

The dose also needs to be interpreted correctly. This was not a trial of full-intensity anticoagulation for atrial fibrillation or treatment of venous thromboembolism. It tested a low-dose cardiovascular-prevention strategy. TRACK therefore does not answer whether an individual with advanced CKD should receive anticoagulation for a separate, established indication; those decisions involve different evidence, doses, alternatives and risk calculations.

Nor does the trial imply that all cardiovascular prevention should be de-emphasized in advanced CKD. It narrows one proposed approach. Blood pressure management, lipid-lowering therapy when indicated, diabetes treatment, smoking cessation and management of established coronary or peripheral artery disease remain separate questions governed by their own evidence.

What the findings support in practice

For policy and formulary decisions, TRACK argues against treating advanced CKD as an automatic indication for rivaroxaban 2.5 mg twice daily. A broad protocol that adds the drug solely because cardiovascular risk is high would expose patients to more major bleeding without a proven reduction in cardiovascular events.

For clinicians, the finding supports separating primary cardiovascular prevention from established anticoagulation indications. A patient receiving rivaroxaban for atrial fibrillation, venous thromboembolism or another recognized indication is not in the same decision pathway as someone being considered for low-dose rivaroxaban solely to prevent vascular events. TRACK addresses the latter strategy.

Medication review remains important because patients with advanced CKD often receive multiple agents that affect hemostasis. Antiplatelet drugs, nonsteroidal anti-inflammatory drugs and anticoagulants can compound bleeding risk, while dialysis access and planned procedures add practical complexity. TRACK does not provide a reason to stop an indicated therapy without reassessment, but it removes support for routine preventive addition of low-dose rivaroxaban in the studied population.

The result also reinforces a regulatory principle: a dose supported for selected coronary or peripheral artery disease populations should not be generalized beyond the kidney-function range and clinical context represented by reliable trial evidence. “Low dose” does not mean low risk, particularly when renal function is severely impaired.

Limits and remaining uncertainties

The trial should be interpreted within its eligibility criteria, outcome definitions, treatment adherence and duration of follow-up. Results from a combined advanced-CKD population may not establish identical relative effects in every subgroup, including nondialysis stage 4 CKD, stage 5 CKD and different dialysis modalities. Subgroup estimates can also be imprecise when event counts are limited.

TRACK tested one drug, one dose and one prevention strategy. It does not determine whether another anticoagulant, a different antithrombotic combination or a biomarker-selected approach could produce a better net outcome. It also should not be used to infer comparative safety among treatments for atrial fibrillation or venous thromboembolism.

Future work may clarify whether narrowly defined advanced-CKD groups have a favorable benefit-risk profile, but such a hypothesis would require prospective testing. Until then, high cardiovascular risk alone is insufficient justification for routine low-dose rivaroxaban when the randomized evidence shows no cardiovascular reduction and more major bleeding.

Questions clinicians ask

Should rivaroxaban 2.5 mg twice daily be added because a dialysis patient has high cardiovascular risk?

TRACK does not support that approach. In advanced CKD and dialysis-dependent kidney failure, the low-dose strategy failed to reduce cardiovascular events and increased major bleeding, so elevated baseline cardiovascular risk by itself does not establish a favorable net benefit.

Does TRACK apply to anticoagulation for atrial fibrillation or venous thromboembolism?

Not directly. TRACK evaluated low-dose rivaroxaban for cardiovascular prevention, not therapeutic anticoagulation for atrial fibrillation or acute venous thromboembolism. Those indications require separate consideration of kidney function, labeling, comparative evidence, thrombotic risk and bleeding risk.

Can COMPASS or VOYAGER PAD results be extrapolated to advanced CKD?

They provide the rationale for vascular-dose rivaroxaban in selected atherosclerotic disease settings, but they do not override TRACK’s direct evidence in advanced CKD. Differences in kidney function, competing cardiovascular mechanisms and baseline bleeding risk can materially change the balance of benefit and harm.

Does the result rule out all antithrombotic prevention in advanced CKD?

No. It argues against routinely adding this rivaroxaban regimen for cardiovascular prevention in the population studied. Decisions about antiplatelet therapy or anticoagulation for another established indication remain distinct and should be based on the evidence and safety considerations relevant to that indication.

References

1. Low-dose rivaroxaban fails to reduce cardiovascular events and increases bleeding in advanced CKD (TRACK trial) — JAMA, 2026
2. Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease — The New England Journal of Medicine, 2017
3. Rivaroxaban in Peripheral Artery Disease after Revascularization — The New England Journal of Medicine, 2020