Adverse Drug Reactions Associated with Rivaroxaban Combined with Common Antithrombotic Agents: A FAERS Database Analysis

This study evaluates the adverse drug reactions (ADRs) associated with rivaroxaban use, both as monotherapy and in combination with antiplatelet agents. The focus is on the frequency and severity of ADRs, particularly hemorrhagic and thrombotic events, across different treatment regimens. Data from the FDA Adverse Event Reporting System (FAERS) between 2014 and 2023 were analyzed. The study population was divided into four groups: rivaroxaban alone, rivaroxaban with aspirin, rivaroxaban with clopidogrel, and triple therapy (rivaroxaban + aspirin + clopidogrel). Disproportionality analysis was used to assess ADRs across treatment groups. Our findings reveal significant variations in ADR incidence, especially gastrointestinal and vascular disorders, highlighting the amplified risk associated with combination therapies. Triple therapy involving rivaroxaban, clopidogrel, and aspirin shows the highest risk for gastrointestinal disorders, with Reporting Odds Ratio (ROR) = 4.89; Proportional Reporting Ratio (PRR) = 3.63; 3,764 cases, providing new evidence of heightened adverse event risks not extensively reported before. The study also identifies rare but severe events, such as splenic hematoma (ROR = 46.45; PRR = 46.44; 45 cases) and ventricular asystole (ROR = 125.83; PRR = 125.79; 4 cases), underscoring the need for vigilant monitoring. These results emphasize the importance of personalized treatment planning and careful risk assessment, particularly for older patients and those with increased bleeding risk, to optimize the safety and efficacy of anticoagulant therapy.