What were the key findings of the TRACK trial?

← Back

TRACK

Low-Dose Rivaroxaban and Cardiovascular Events in Advanced Kidney Disease: The TRACK Randomized Clinical Trial

Share Share Copied! Compare

Year of Publication: 2026

Authors: Badve SV, Perkovic V, Jha V, et al. (TRACK Trial Investigators)

Journal: JAMA

Citation: JAMA. 2026;336(4):296-305. doi:10.1001/jama.2026.9379

Link: https://doi.org/10.1001/jama.2026.9379

Bottom Line

In patients with advanced CKD at high cardiovascular risk, low-dose rivaroxaban did NOT reduce the composite of cardiovascular death, MI, stroke, or PAD events, but significantly increased major bleeding (HR 1.51).

        Major Points
        Investigator-initiated, double-blind RCT at 90 centers in 12 countries; 1458 patients randomized (727 rivaroxaban vs 731 placebo).
Trial stopped early on August 7, 2025 by DSMB due to lack of efficacy and net harm concerns (conditional power only 16% for HR 0.78).
Primary composite outcome (CV death, nonfatal MI, stroke, or nonfatal PAD event) occurred in 22.6% vs 20.7% (HR 1.09, 95% CI 0.87-1.36, P=.46) — no benefit.
Major bleeding significantly increased: 8.8% vs 6.0% (HR 1.51, 95% CI 1.02-2.22, P=.04); intracranial bleeding 6 vs 3.
VTE significantly reduced with rivaroxaban: 0.6% vs 1.9% (HR 0.29, 95% CI 0.09-0.87).
Bleeding risk was even higher in patients ≥65 years (interaction P=.03).
Findings contrast with COMPASS/VOYAGER PAD — antithrombotic decisions in advanced CKD should not be extrapolated from other CV populations.

      

Design

Study Type: Randomized Controlled Trial

Randomization: 1

Blinding: Double-blind, placebo-controlled

Enrollment Period: January 18, 2021 - July 31, 2025 (stopped early)

Follow-up Duration: Median 1.7 years (IQR 0.9-2.8)

Centers: 90

Countries: Australia, Belgium, Canada, France, Germany, India, Malaysia, Nepal, Saudi Arabia, Singapore, Taiwan, Tunisia

Sample Size: 1458

Analysis: Intention-to-treat (shared-frailty Cox model with random site effect)

Inclusion Criteria

Adults aged ≥18 years
Dialysis-dependent kidney failure OR CKD stage 4-5 not receiving kidney replacement therapy (eGFR ≤29 mL/min/1.73 m²)
At least 1 of the following cardiovascular risk factors: coronary artery disease, nonhemorrhagic nonlacunar stroke, peripheral artery disease, diabetes, or age ≥65 years
Successful completion of 21-day placebo run-in phase (≥80% adherence)
Written informed consent

Exclusion Criteria

Mechanical or prosthetic heart valve (except bioprosthetic)
Indication for or contraindication to anticoagulant therapy
High bleeding risk per treating clinician; major bleeding within past 30 days or active major bleeding
History of hemorrhagic or lacunar stroke; any stroke within past month
Treatment with P2Y12 inhibitor or phosphodiesterase inhibitor that could not be discontinued; concurrent strong CYP3A4/P-gp inhibitors or CYP3A4 inducers
Severe heart failure (LVEF <30% or NYHA III/IV); uncontrolled hypertension (SBP ≥180 or DBP ≥110 mm Hg)
Hemoglobin <90 g/L; platelets <100 × 10⁹/L; significant liver disease (Child-Pugh B/C) or ALT >3× ULN
Kidney transplant with functioning allograft or scheduled living-donor transplant; pregnancy/breastfeeding
Atrial fibrillation with indication for therapeutic anticoagulation

Baseline Characteristics

Characteristic	Control	Active
Mean Age	63.1 years (SD 11.6)	63.3 years (SD 11.7)
Sex - Female	29.3% (214)	30.0% (218)
Race - Asian	32.7%	31.1%
Race - Indian subcontinent	35.8%	35.6%
Race - White	24.4%	27.8%
Mean BMI	26.7	26.5
Systolic BP (mm Hg)	140.2 (SD 17.6)	139.0 (SD 16.8)
Nondialysis-dependent CKD	50.9%	51.0%
Dialysis-dependent kidney failure	49.1% (hemodialysis 40.8%, PD 8.3%)	49.0% (hemodialysis 40.0%, PD 8.9%)
Diabetes	77.4%	77.9%
Age ≥65 y	48.8%	47.2%
Coronary artery disease	19.6%	17.7%
Prior nonhemorrhagic nonlacunar stroke	6.8%	6.5%
Peripheral artery disease	5.6%	6.6%
Atrial fibrillation	4.3%	4.3%
Congestive heart failure	6.7%	5.7%
Current smoking	7.3%	7.2%
Aspirin use	46.2%	46.6%
Lipid-lowering agents	59.9%	59.7%

Arms

Field	Low-dose rivaroxaban	Control
Intervention	Rivaroxaban 2.5 mg twice daily	Matching placebo twice daily
Duration	Median 1.7 years follow-up	Median 1.8 years follow-up

Outcomes

Outcome	Type	Control	Intervention	HR / OR / RR	P-value
Composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or nonfatal peripheral artery disease event	Primary	20.7% (151/731); 11.8 per 100 py	22.6% (164/727); 13.0 per 100 py	1.09	0.46
All-cause mortality	Secondary	23.0% (168)	25.6% (186)	1.14	0.66 (Holm-Šídák)
Cardiovascular death	Secondary	13.3% (97)	15.4% (112)	1.18	0.68
Myocardial infarction	Secondary	5.6% (41)	5.4% (39)	0.94	0.77
Stroke (any)	Secondary	2.2% (16)	2.6% (19)	1.19	0.85
Ischemic/uncertain stroke	Secondary	1.9% (14)	1.9% (14)	1.02
Hemorrhagic stroke	Secondary	0.3% (2)	0.7% (5)	1.98
Peripheral artery disease event	Secondary	3.0% (22)	2.1% (15)	0.69
CV death + MI + stroke	Secondary	18.7% (137)	21.1% (154)	1.14
Venous thromboembolism	Secondary	1.9% (14)	0.6% (4)	0.29
Thrombosis of dialysis vascular access (among HD patients)	Secondary	5.4% (16/298)	7.6% (22/291)	1.44
Net clinical benefit (CV death, MI, stroke, PAD event, fatal bleeding, or symptomatic critical-organ bleeding)	Secondary	21.3% (156)	24.2% (176)	1.14	0.25
Major bleeding	Adverse	8.8% rivaroxaban vs 6.0% placebo (5.1 vs 3.4 per 100 py; HR 1.51, 95% CI 1.02-2.22, P=.04)
Gastrointestinal bleeding	Adverse	4.0% vs 2.3% (2.2 vs 1.3 per 100 py; HR 1.76, 95% CI 0.96-3.22, P=.07)
Intracranial bleeding	Adverse	6 (rivaroxaban) vs 3 (placebo)
Serious adverse events	Adverse	50.5% (367 patients, 934 events) rivaroxaban vs 45.8% (335 patients, 936 events) placebo
Permanent discontinuation of study medication	Adverse	28.9% rivaroxaban vs 27.5% placebo
Sudden cardiac death (most common cause of death)	Adverse	39.8% of deaths in rivaroxaban group; 44.6% in placebo group

Subgroup Analysis

Primary outcome consistent across age, sex, region, aspirin use, diabetes, CKD stage, and smoking status. Bleeding risk was significantly higher in patients ≥65 years (rivaroxaban 10% vs placebo 5.6%) than younger patients (7.3% vs 6.4%; interaction P=.03).

Criticisms

Trial stopped early for futility/net harm at 49.3% of expected events — treatment effect estimates are less precise and inferences should be interpreted cautiously.
High rate of permanent study drug discontinuation (~28% in both groups) may have reduced power to detect a treatment benefit.
Rivaroxaban was tested alone, not combined with aspirin (unlike COMPASS/VOYAGER PAD), which may partly explain the null result.
About half of participants had no established cardiovascular disease (enrolled based on diabetes or age ≥65 alone), diluting a potential effect.
No participants from the US and no participants identifying as Black were enrolled — limits generalizability.
42.1% of all deaths were sudden cardiac deaths, which may not be modifiable by antithrombotic therapy.
Minor bleeding data were not collected; formal adherence assessment limited by COVID-19 pandemic.

Funding

NHMRC of Australia (2018/GNT1162375), French Ministry of Health PHRC-19-0112, Deutsche Forschungsgemeinschaft (506165771). Rivaroxaban and placebo tablets provided by Bayer AG free of cost through the Investigator-Initiated Research Support Scheme. Funders had no role in design, conduct, analysis, or reporting.

Based on: TRACK (JAMA, 2026)

Authors: Badve SV, Perkovic V, Jha V, et al. (TRACK Trial Investigators)

Citation: JAMA. 2026;336(4):296-305. doi:10.1001/jama.2026.9379

Content summarized and formatted by NeuroTrials.ai.

TRACK

(2026)

Objective

To determine whether low-dose rivaroxaban (2.5 mg twice daily) reduces major adverse cardiovascular events (including stroke) compared with placebo in patients with advanced chronic kidney disease (CKD stage 4-5 or dialysis-dependent kidney failure).

Study Summary

• Primary composite outcome (CV death, nonfatal MI, stroke, or PAD event): 22.6% rivaroxaban vs 20.7% placebo (HR 1.09, 95% CI 0.87-1.36, P=.46) — no benefit
• Stroke: 2.6% rivaroxaban vs 2.2% placebo (HR 1.19, 95% CI 0.61-2.31)
• Major bleeding significantly increased: 8.8% vs 6.0% (HR 1.51, 95% CI 1.02-2.22, P=.04)
• Trial stopped early on August 7, 2025 for lack of efficacy and net harm concerns

Intervention

Rivaroxaban 2.5 mg twice daily

Inclusion Criteria

Adults ≥18 years with CKD stage 4-5 (eGFR ≤29 mL/min/1.73 m²) or dialysis-dependent kidney failure, plus ≥1 of: coronary artery disease, nonhemorrhagic nonlacunar stroke, peripheral artery disease, diabetes, or age ≥65 years.

Study Design

Arms: Rivaroxaban 2.5 mg BID vs matching placebo (1:1 randomization, double-blind)

Patients per Arm: 727 rivaroxaban, 731 placebo (total 1458)

Outcome

• Primary composite endpoint: 13.0 vs 11.8 events per 100 person-years (HR 1.09, P=.46) — no reduction
• All-cause mortality: 25.6% vs 23.0% (HR 1.14)
• Cardiovascular death: 15.4% vs 13.3% (HR 1.18)
• Venous thromboembolism significantly lower: 0.6% vs 1.9% (HR 0.29, 95% CI 0.09-0.87)
• Major bleeding significantly higher: 5.1 vs 3.4 per 100 py (HR 1.51, P=.04)

Clinical Question

In patients with advanced CKD (stage 4-5 or dialysis) at high cardiovascular risk, does low-dose rivaroxaban (2.5 mg BID) reduce major adverse cardiovascular events compared with placebo?

Bottom Line

Major Points

Investigator-initiated, double-blind RCT at 90 centers in 12 countries; 1458 patients randomized (727 rivaroxaban vs 731 placebo).
Trial stopped early on August 7, 2025 by DSMB due to lack of efficacy and net harm concerns (conditional power only 16% for HR 0.78).
Primary composite outcome (CV death, nonfatal MI, stroke, or nonfatal PAD event) occurred in 22.6% vs 20.7% (HR 1.09, 95% CI 0.87-1.36, P=.46) — no benefit.
Major bleeding significantly increased: 8.8% vs 6.0% (HR 1.51, 95% CI 1.02-2.22, P=.04); intracranial bleeding 6 vs 3.
VTE significantly reduced with rivaroxaban: 0.6% vs 1.9% (HR 0.29, 95% CI 0.09-0.87).
Bleeding risk was even higher in patients ≥65 years (interaction P=.03).
Findings contrast with COMPASS/VOYAGER PAD — antithrombotic decisions in advanced CKD should not be extrapolated from other CV populations.

Study Design

Study Type: Randomized Controlled Trial
Randomization: Yes
Blinding: Double-blind, placebo-controlled
Sample Size: 1458
Follow-up: Median 1.7 years (IQR 0.9-2.8)
Centers: 90
Countries: Australia, Belgium, Canada, France, Germany, India, Malaysia, Nepal, Saudi Arabia, Singapore, Taiwan, Tunisia

Primary Outcome

Definition: Composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or nonfatal peripheral artery disease event

Control	Intervention	HR/OR	P-value
20.7% (151/731); 11.8 per 100 py	22.6% (164/727); 13.0 per 100 py	1.09 (0.87-1.36)	0.46

Limitations & Criticisms

Trial stopped early for futility/net harm at 49.3% of expected events — treatment effect estimates are less precise and inferences should be interpreted cautiously.
High rate of permanent study drug discontinuation (~28% in both groups) may have reduced power to detect a treatment benefit.
Rivaroxaban was tested alone, not combined with aspirin (unlike COMPASS/VOYAGER PAD), which may partly explain the null result.
About half of participants had no established cardiovascular disease (enrolled based on diabetes or age ≥65 alone), diluting a potential effect.
No participants from the US and no participants identifying as Black were enrolled — limits generalizability.
42.1% of all deaths were sudden cardiac deaths, which may not be modifiable by antithrombotic therapy.
Minor bleeding data were not collected; formal adherence assessment limited by COVID-19 pandemic.

Citation

JAMA. 2026;336(4):296-305. doi:10.1001/jama.2026.9379

View Original Publication →

TRACK

Low-Dose Rivaroxaban and Cardiovascular Events in Advanced Kidney Disease: The TRACK Randomized Clinical Trial

Bottom Line

Major Points

Design

Inclusion Criteria

Exclusion Criteria

Baseline Characteristics

Arms

Outcomes

Subgroup Analysis

Criticisms

Funding

Ask about TRACK