Highlights
- •Data supporting the use of DOACs in patients with extreme obesity are lacking
- •Current guidelines suggest measurements of DOACs levels in morbidly obese patients
- •Patients with extreme obesity and atrial fibrillation on DOACs therapy show DOAC's plasma concentration in the expected range.
- •There is no correlation between plasma concentration in extreme obese patients and the hyperfiltrating patients (clearance of creatinine>95 ml/min).
- •DOACs inappropriate underdosing is the only predictor of DOACs plasma concentration out of the expected range.
Abstract
Purpose
Direct oral anticoagulants (DOACs) are recommended in preference to vitamin K antagonists
(VKAs) for stroke prevention in patients with atrial fibrillation (AF) eligible for
oral anticoagulation therapy; however, data and clinical experiences supporting the
use of DOACs in patients with a body mass index ≥40 kg/m2 or weight >120 kg remain limited. The aim of this study was to evaluate the pharmacokinetic
properties of DOACs in patients with AF and extreme obesity.
Methods
We enrolled all consecutive patients with AF and extreme obesity undergoing treatment
with DOACs followed up at Monaldi Hospital, Naples, Italy. To determine peak plasma
and trough levels of DOACs, plasma samples were collected at 2nd, 4th, 6th, and 12th
hours from the last dose intake in patients receiving apixaban and dabigatran and
at the 2nd, 4th, 6th, and 24th hours in those receiving edoxaban and rivaroxaban.
The DOACs’ peak and trough plasma levels obtained from our study population were compared
with those sourced from pharmacokinetic studies among patients without obesity, defined
as a normal reference range in the literature. If at least 1 peak or trough plasma
level was found below or above the normal reference ranges, the patients were classified
as having out-of-range DOAC plasma levels. Study population was then divided into
in-range and out-of-range groups. Baseline characteristics, including DOAC treatment,
were compared between the 2 groups. Univariate and multivariate logistic regression
analysis were performed to identify baseline variables associated with DOACs’ plasma
concentration out of the expected range.
Findings
A total of 58 patients (mean [SD] age, 70.93 [8.73] years; 40% female) with extreme
obesity (mean [SD] body mass index. 44.43 [3.54] kg/m2) and AF while undergoing DOAC treatment were included in the present study. In 9
patients (15.5 %), the DOAC plasma concentrations were out of the expected ranges
(out-of-range group);, indicating a greater likelihood of edoxaban 30 mg treatment
(33% vs 2%; P < 0.01) and inappropriate DOAC underdosing (56% vs 4%; P < 0.005) compared with the in-range group. According to the multivariate logistic
analysis (P = 0.0011), the inappropriate DOAC underdosing (hazard ratio = 29.37; P = 0.0002) was an independent predictor of DOAC plasma levels out of the expected
ranges.
Implications
Patients with extreme obesity and AF who were receiving DOAC therapy had DOAC plasma
concentrations in the expected range. The inappropriate DOAC underdosing seems to
be the only independent clinical factor associated with a plasma concentration of
the drug out of the expected range.
Key words
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Article info
Publication history
Published online: August 05, 2021
Accepted:
July 5,
2021
Identification
Copyright
© 2021 Elsevier Inc.
