Predictors associated with bleeding and thromboembolic complications in
patients taking rivaroxaban-- a Singapore study
Abstract
Aims: In a previous study, Singaporean Asians were found to have lower
rivaroxaban plasma concentrations than Caucasians. This study attempts
to identify predictors that may be 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. 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 analyze 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 six-fold 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 modeling are required to
investigate the drug-drug interactions between these drugs. Keywords:
Atrial Fibrillation, Bleeding, Rivaroxaban, Simvastatin