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A systematic review and meta-analysis of the morbidity of efficacy endpoints and bleeding events in elderly and young patients treated with the same dose rivaroxaban

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Abstract

Rivaroxaban is a new direct oral anticoagulant, and the same dose is recommended for older and young patients. However, recent real-world studies show that older patients may need dose adjustment to prevent major bleeding. At present, the evidence for dose adjustment in older patients is extremely limited with only a few reports on older atrial fibrillation patients. The aim of this study was to review the morbidity data of adverse events and bleeding events across all indications for older and young patients treated with the same dose of rivaroxaban to provide some support for dosage adjustment in older patients. The PubMed, EMBASE, ClinicalTrials, Cochrane and Web of Science databases were searched for randomized controlled trials (RCTs) published between January 1, 2005, and October 10, 2023. The primary outcomes were the morbidity of bleeding events and efficacy-related adverse events. Summary estimates were calculated using a random effects model. Eighteen RCTs were included in the qualitative analysis. The overall morbidity of primary efficacy endpoints was higher in older patients compared to the young patients (3.37% vs. 2.60%, χ2 = 5.24, p = 0.022). Similarly, a higher morbidity of bleeding was observed in older patients compared to the young patients (4.42% vs. 6.03%, χ2 = 13.22, p < 0.001). Among all indications, deep vein thrombosis, pulmonary embolism and atrial fibrillation were associated with the highest incidence of bleeding in older patients, suggesting that these patients may be most need dose adjustment. Patients older than 75 years may require extra attention to prevent bleeding. The same dose of rivaroxaban resulted in higher bleeding morbidity and morbidity of efficacy-related adverse events in older patients compared to the young patients. An individualized dose adjustment may be preferred for older patients rather than a fixed dose that fits all.

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Funding

This work was supported by the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (grant numbers, CIFMS 2021-I2M-1-003) and the National High Level Hospital Clinical Research Funding (grant numbers, 2022-PUMCH-B-033).

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Authors and Affiliations

  1. Clinical Pharmacology Research Center, Beijing Key Laboratory of Clinical PK and PD Investigation for Innovative Drugs, NMPA Key Laboratory for Clinical Research and Evaluation of Drug, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China

    Jianwei Ren, Na Wang, Xuan Zhang, Xin Zheng & Xiaohong Han

  2. Center for Food and Drug Inspection, National Medical Products Administration, Beijing, 100053, China

    Fuyu Song

  3. NHC Key Laboratory of Mental Health, National Clinical Research Center for Mental Disorders, Peking University Sixth Hospital, Peking University Institute of Mental Health, Peking University, Beijing, 100191, China

    Fuyu Song

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  1. Jianwei Ren
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  2. Na Wang
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  3. Xuan Zhang
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  4. Fuyu Song
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  5. Xin Zheng
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  6. Xiaohong Han
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Contributions

X.H. conceptualised and designed the study and drafted the protocol. N.W. and X.Z. performed the study selection, quality assessment and data extraction. J.R. and F.S. performed the statistical analyses. J.R. and X.Z. drafted the initial version of the manuscript, which was reviewed and edited by all authors.

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Correspondence to Xin Zheng or Xiaohong Han.

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Ren, J., Wang, N., Zhang, X. et al. A systematic review and meta-analysis of the morbidity of efficacy endpoints and bleeding events in elderly and young patients treated with the same dose rivaroxaban. Ann Hematol (2024). https://doi.org/10.1007/s00277-024-05767-z

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