Results
Out of 146 patients recruited for the study, 134 patients (91.8%) were
included (97 patients taking rivaroxaban, 37 patients taking apixaban).
Patients who were lost to follow-up, had their DOAC changed, stopped or
down-titrated were excluded (Fig. 1).
Baseline demographics of all 146 patients are reported in Table 1.
Patient characteristics were similar for rivaroxaban and apixaban
patients. Three patients out of 134 included for analysis experienced
SSE events (2.2%), while 33 experienced bleeds (24.6%).
We compared the characteristics of patients with and without bleeding
events for both DOACs. For the rivaroxaban cohort, CrCl and concomitant
use of simvastatin were statistically significant factors associated
with bleeding (p = 0.047 and 0.024 respectively) (Table 2). Further
information on the frequencies of patients who bled in each individual
class is described in Supplementary Table S1. We did not carry out
further analyses for the apixaban cohort because there were no
significant factors associated with bleeding in the cohort
(Supplementary Table S2).
Table 3 shows the multivariable analysis for risk of bleeding with
rivaroxaban. After controlling for BMI, CrCl and previous SSE,
concomitant use of simvastatin (compared with patients not on statins)
remained as the only significant predictor of bleeding [Adjusted OR =
6.14 (95% CI: 1.18 – 31.97), p = 0.031]. Although not statistically
significant, patients with previous SSE events seemed to have a
four-fold lower risk of bleeding [Adjusted OR = 0.25 (95% CI: 0.05 –
1.27), p = 0.094].
Comparing rivaroxaban plasma concentrations in patients with or without
concomitant simvastatin use, median peak rivaroxaban plasma
concentration in simvastatin patients was significantly higher compared
to patients not on simvastatin (Table 4). Trough plasma concentrations
were not significantly different between groups.
There was no statistically significant difference in median rivaroxaban
plasma concentrations with or without concomitant use of atorvastatin
(Supplementary Table S3). There were too few patients with concomitant
use of rosuvastatin for comparison to be done.
Table 5 describes the trough concentrations and
CHA2DS2-VASc scores of the three
patients with SSE. These patients had low trough plasma concentrations
of between 8.1% and 26.8% of the populations’ median concentrations
for the respective DOACs. No further analyses were carried out to
compare these patients as there were too few events for substantial
comparison.