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Cardiovascular Drugs and Therapy
Published in: Cardiovascular Drugs and Therapy 5/2023

14-05-2022 | Atorvastatin | Original Article

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

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

Published in: Cardiovascular Drugs and Therapy | Issue 5/2023

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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.
Appendix
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Metadata
Title
Simvastatin, but Not Atorvastatin, Is Associated with Higher Peak Rivaroxaban Serum Levels and Bleeding: an Asian Cohort Study from Singapore
Authors
Xin Qin Soh
Doreen Su-Yin Tan
Eric Chun Yong Chan
Publication date
14-05-2022
Publisher
Springer US
Published in
Cardiovascular Drugs and Therapy / Issue 5/2023
Print ISSN: 0920-3206
Electronic ISSN: 1573-7241
DOI
https://doi.org/10.1007/s10557-022-07346-8

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