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Simvastatin, but Not Atorvastatin, Is Associated with Higher Peak Rivaroxaban Serum Levels and Bleeding: an Asian Cohort Study from Singapore

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Abstract

Aims

This study attempts to identify predictors associated with bleeding and stroke and systemic embolism (SSE) in Singaporean Asians taking rivaroxaban and apixaban.

Methods

A total of 134 Singaporean patients on either rivaroxaban or apixaban for non-valvular atrial fibrillation were included for this study. Baseline characteristics were recorded at recruitment while bleeding and SSE events were recorded during a 1-year follow-up. Peak and trough drug plasma concentrations were collected based on the dosing interval and pharmacokinetics of the drugs and quantified using high performance liquid chromatography. Characteristics of patients with or without bleeds were compared using relevant statistical tests. Multivariable regression that included covariates with p < 0.1 from an initial univariable regression was performed to analyse predictors that resulted in higher risk of bleeding in patients.

Results

Median creatinine clearance (CrCl) was significantly lower in patients on rivaroxaban who experienced bleeds as compared to patients who did not experience bleeds (61.5 vs 70.8 mL/min, p = 0.047), while concomitant simvastatin use was found to be independently associated with a sixfold increased risk of bleeding (adjusted OR = 6.14 (95% CI: 1.18–31.97), p = 0.031) for rivaroxaban after controlling for body mass index, CrCl and having experienced a previous SSE.

Conclusion

Our findings suggest that concomitant use of simvastatin with rivaroxaban may be associated with bleeding events in an Asian cohort. Further studies using physiologically based pharmacokinetic modelling are required to investigate the drug-drug interactions between these drugs.

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Data Availability

The datasets generated during and/or analysed during the current study are not publicly available due to privacy or ethical restrictions but are available from the corresponding author on reasonable request.

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Acknowledgements

The authors wish to extend their thanks to Ms Lin Yingying (Khoo Teck Puat Hospital) for her help with data collection and data preparation for this study.

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Authors and Affiliations

  1. National University of Singapore, 18 Science Drive 4, Singapore City, 117559, Singapore

    Xin Qin Soh, Doreen Su-Yin Tan & Eric Chun Yong Chan

Authors
  1. Xin Qin Soh
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  2. Doreen Su-Yin Tan
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  3. Eric Chun Yong Chan
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Contributions

Participated in research design: XQ Soh, DSY Tan and ECY Chan. Performed data analysis: XQ Soh. Wrote or contributed to the writing of the manuscript: XQ Soh, DSY Tan and ECY Chan.

Corresponding author

Correspondence to Xin Qin Soh.

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Ethics Approval and Consent to Participate

Ethics approval was obtained from the Domain Specific Review Board (Study reference number: 2017/00815). Informed consent by participants was obtained prior to data collection.

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The authors declare no competing interests.

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Soh, X.Q., Tan, D.SY. & Chan, E.C.Y. Simvastatin, but Not Atorvastatin, Is Associated with Higher Peak Rivaroxaban Serum Levels and Bleeding: an Asian Cohort Study from Singapore. Cardiovasc Drugs Ther 37, 917–925 (2023). https://doi.org/10.1007/s10557-022-07346-8

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