S V Badve, Sunil V. Badve, Vlado Perkovic, Vivekanand Jha, Raja Ramachandran, Lily Mushahar, Jan Menne, An S. De Vriese, Patrick Rossignol, Adrien Flahault, Maha Al Ammari, Habib Skhiri, Michael Walsh, David Collister, Adrian Liew, Laurent Billot, Severine Bompoint, Anthony Devaux, Min Jun, Enmoore Lin, Aline Ramos da Cruz, Jeffrey T. Ha, John W. Eikelboom, Ahmed Shaman, Meg J. Jardine, Shilpanjali Jesudason, Muh Geot Wong, Craig S. Anderson, Amit X. Garg, Hiddo J. L. Heerspink, Helen Monaghan, Anushka Patel, Patrick B. Mark, David C. Wheeler, Li Zuo, Li Zuo, Helen Pilmore, Martin Gallagher, TRACK Trial Investigators, Sunil Badve, Sunil Badve, Martin Gallagher, Vlado Perkovic, Vivekanand Jha, Raja Ramachandran, Lily Mushahar, Jan Menne, An S. De Vriese, Patrick Rossignol, Adrien Flahault, Maha Al Ammari, Ahmed Shaman, Habib Skhiri, Michael Walsh, David Collister, Adrian Liew, Laurent Billot, Min Jun, Enmoore Lin, Jeffrey Ha, Meg Jardine, Shilpa Jesudason, Muh Geot Wong, John Eikelboom, Craig Anderson, Anushka Patel, Helen Monaghan, Amit Garg, Hiddo Heerspink, Patrick Mark, David Wheeler, Jicheng Lv, Li Zuo, Helen Pilmore, Glenn Chertow, Kenneth Mahaffy, Kimberly Walters, David Johnson, Clare Arnott, Monica Badve, Amanda Hugman, Lubomyr Lemech, Freda Passam, Amanda Siriwardana, Wing Yeung, Alexandra Gallagher, Daniel O'Hara, Stéphane Zuily, Sébastien Richard, Jessica Sun, Hans Van Der Meersch, Hans Lorenzen, Aline Ramos da Cruz, Manuela Armenis, Arlen Wilcox, Sedricx Fontanilla, Alison Coenen, Martyn Ralph, Namrata Kumar, Hong Man
Importance: Approximately 10% to 15% of patients with advanced chronic kidney disease (CKD) experience a fatal or nonfatal cardiovascular event annually. The effects of antithrombotic therapies on cardiovascular events in patients with advanced CKD are unknown. Objective: To determine whether low-dose rivaroxaban reduces rates of adverse cardiovascular events compared with placebo in patients with advanced CKD. Design, Setting, and Participants: Randomized, double-blind, placebo-controlled trial conducted at 90 centers in 12 countries. Eligible participants were adults with CKD stage 4 or 5 and patients with dialysis-dependent kidney failure. Participants had a history of either coronary artery disease; nonhemorrhagic, nonlacunar stroke; peripheral artery disease; diabetes; or were 65 years or older. Enrollment occurred between January 2021 and July 2025. The trial was stopped early on August 7, 2025, for lack of efficacy. Final follow-up occurred on October 30, 2025. Statistical analyses were conducted in February and March 2026. Interventions: Patients were randomized 1:1 to receive rivaroxaban 2.5 mg twice daily or placebo. Main Outcomes and Measures: The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, stroke, or a peripheral artery disease event. The primary safety outcome was major bleeding. Results: Of 1458 randomized patients (mean [SD] age, 63.2 [11.6] years, 432 [29.6%] female), 1360 (93.3%) completed follow-up. During a median follow-up of 1.7 years, the primary outcome occurred in 164 patients (22.6%) in the low-dose rivaroxaban group and 151 (20.7%) in the placebo group (13.0 vs 11.8 events per 100 person-years; hazard ratio, 1.09 [95% CI, 0.87-1.36]; P = .46). Major bleeding occurred in 64 patients (8.8%) receiving low-dose rivaroxaban and 44 (6.0%) receiving placebo (5.1 vs 3.4 events per 100 person-years; hazard ratio, 1.51 [95% CI, 1.02-2.22]; P = .04). Conclusions and Relevance: In patients with advanced CKD at high cardiovascular risk, low-dose rivaroxaban did not reduce the risk of a composite cardiovascular outcome. Major bleeding rates were significantly higher in the low-dose rivaroxaban group compared with the placebo group. Trial Registration: ClinicalTrials.gov Identifier: NCT03969953.