Apixaban plasma concentrations in patients with obesity

Abstract

Purpose: Routine therapeutic drug monitoring of apixaban is currently not recommended but may however be warranted in some situations and for some patient groups to provide better and safer treatment. Due to limited data on apixaban concentrations in different subpopulations, it is still unclear which group of patients could possibly gain from monitoring. The purpose of this study was to examine apixaban exposure in patients with obesity compared with normal-weight patients.

Methods: Forty patients with obesity (mean BMI 39.4 kg/m²) and 40 controls with normal weight (mean BMI 23.4 kg/m²), treated with apixaban 5 mg twice daily were included. The patients were matched for age, sex, and renal function. Trough and peak apixaban concentrations were measured with LC‒MS/MS methodology.

Results: The median trough concentrations in patients with obesity (58.7, range 10.7-200.7 ng/ml) were slightly higher than those in patients with normal weight (52.0, range 31.0-150.9 ng/ml) (p < 0.05). Notably, the variability in trough concentration was considerably higher in patients with obesity. Peak concentrations were similar in both groups, with a median of 124.5 ng/ml (range 82.0-277.5) and 113.5 ng/ml (range 75.5-334.6) in patients with obesity and normal weight, respectively.

Conclusion: Apixaban exposure did not vary substantially between obese and normal weight matched controls, implying that general dose adjustments are not required. However, vast interindividual variability was observed in patients with obesity, suggesting that measuring the concentrations could be valuable for specific patients. Further research is needed to identify which specific patients may benefit from this approach.

Keywords: Apixaban; Body weight; Obesity; Plasma concentration; Therapeutic drug monitoring.

Fig. 1

Apixaban trough concentrations measured in 40 patients with obesity and 40 matched normal weight patients treated with apixaban 5 mg twice daily. The line inside the box plot represents the median, and the top and bottom lines of the box show Q1 (25th percentile) and Q3 (75th percentile). The whiskers represent minimum and maximum values excluding outliers. Mild outliers (circle) are defined as values outside the ranges from 1.5 × interquartile range (IQR) below Q1 or above Q3

Fig. 2

Correlation between apixaban trough concentrations and BMI/weight in 40 patients with obesity and 40 matched normal weight patients treated with apixaban 5 mg twice daily

Fig. 3

Apixaban peak concentrations measured with LC‒MS/MS methodology in 22 pairs of patients with obesity and normal weight patients treated with apixaban 5 mg twice daily. The line inside the box plot represents the median, and the top and bottom lines of the box show Q1 (25th percentile) and Q3 (75th percentile). The whiskers represent minimum and maximum values excluding outliers. Mild outliers are defined as values outside the ranges from 1.5 × interquartile range (IQR) below Q1 or above Q3. Extreme outliers (star) are defined as values outside the ranges from 3 × IQR below Q1 or above Q3

Fig. 4

Correlation between apixaban peak concentrations and BMI/weight in 22 patients with obesity and 22 matched normal weight patients treated with apixaban 5 mg twice daily

Fig. 5

Correlation between apixaban concentrations at trough and peak in 22 patients with obesity and 22 matched normal weight patients treated with apixaban 5 mg twice daily

Fig. 6

Correlation between apixaban trough concentrations and renal function estimated as relative eGFR in 40 patients with obesity and 40 matched normal weight patients treated with apixaban 5 mg twice daily