Comparative Effectiveness and Pharmacological Fingerprints of Indobufen versus Rivaroxaban in Patients with Chronic Kidney Disease: A Single-Center, Real-World Study

Lijun Zhang¹Mingbo Liu²Tingting Huang³He Zhang¹Chuanfu Huang¹Zhenbin Pan¹Zhao Chen¹Jun Ning¹Jiameng Tang^2*

• ¹Department of Nephrology, The First People's Hospital of Qinzhou, The Tenth Affiliated Hospital of Guangxi Medical University, Qinzhou, China
• ²Department of Laboratory Medicine, The First People's Hospital of Qinzhou, The Tenth Affiliated Hospital of Guangxi Medical University, Qinzhou, China
• ³Department of Medical Statistics, The First People's Hospital of Qinzhou, The Tenth Affiliated Hospital of Guangxi Medical University, Qinzhou, China

Abstract Introduction: Antithrombotic management in Chronic Kidney Disease (CKD) is a clinical dilemma. This study aimed to empirically evaluate the "de facto interchangeability" of the antiplatelet indobufen and the anticoagulant rivaroxaban by comparing their real-world effectiveness and safety in hospitalized CKD patients. Methods: In this retrospective cohort study (2020-2024), we analyzed CKD patients treated with indobufen or rivaroxaban. A multi-stage analysis first used machine learning to assess baseline cohort comparability, overcoming limitations of p-value-based tests. Subsequently, a Linear Mixed Model (LMM), adjusted for confounders including polypharmacy, assessed independent drug effects on in-hospital thrombosis, hemorrhage, and longitudinal laboratory markers. Results: Machine learning demonstrated the clinical comparability of the indobufen and rivaroxaban cohorts. The incidence of in-hospital thrombosis was numerically lower in the indobufen group (3.65% vs. 7.58%; P = 0.101), while hemorrhage rates were similar (2.19% vs. 2.27%; P = 1). The LMM analysis, beyond verifying indobfen's expected antiplatelet activity (modulating MPV, PDW), revealed pleiotropic effects (increased prealbumin, HDL-C) and a significant reduction in urine occult blood (P<0.001), suggesting renal safety. Notably, the model demonstrated that apparent effects on hemoglobin and eGFR were attributable to confounding by co-medications, not a direct drug effect. Conclusion: In this real-world CKD cohort, indobufen and rivaroxaban demonstrated comparable clinical effectiveness and safety. Combining machine learning with longitudinal models helps to statistically adjust for complex confounders like polypharmacy, thereby providing a more robust estimate of a drug's independent effect.