Efficacy, Safety, and Exposure of Apixaban in Patients with High Body Weight or Obesity and Venous Thromboembolism: Insights from AMPLIFY

Abstract

Introduction: As a result of limited clinical data, guidelines do not recommend the use of non-vitamin K antagonist oral anticoagulants in patients who weigh > 120 kg or have a body mass index (BMI) > 40 kg/m².

Methods: This post hoc analysis of the AMPLIFY trial evaluated the efficacy (venous thromboembolism [VTE]/VTE-related death), safety (major and composite of major and clinically relevant non-major [CRNM] bleeding), and exposure of apixaban compared with enoxaparin followed by warfarin for the treatment of VTE by body weight (≤ 60, > 60 to < 100, ≥ 100 to < 120, ≥ 120 kg) and BMI (≤ 25, > 25 to 30, > 30 to 35, > 35 to 40, > 40 kg/m²).

Results: Among the AMPLIFY safety population, 5384 and 5359 patients had recorded body weight (range 28.9 to 222.0 kg; ≥ 120 kg, n = 290) and BMI (range 12.5-71.8 kg/m²; > 40 kg/m², n = 263), respectively. The rates of recurrent VTE/VTE-related death for apixaban versus enoxaparin/warfarin were similar across body weight subgroups: relative risks (RR; 95% confidence intervals [CI]) were 0.63 (0.23, 1.72), 0.99 (0.65, 1.50), 0.77 (0.34, 1.72), and 0.20 (0.02, 1.72) for the ≤ 60, > 60 to < 100, ≥ 100 to < 120, and ≥ 120 kg groups, respectively (P_interaction = 0.44). The rates of major bleeding were lower with apixaban versus enoxaparin/warfarin; RRs (95% CI) were 0.15 (0.02, 1.15), 0.41 (0.21, 0.77), not estimable, and 0.34 (0.04, 3.22), respectively (P_interaction = not estimable). The rates of major/CRNM bleeding were significantly lower for apixaban versus enoxaparin/warfarin; RRs (95% CI) were 0.46 (0.24, 0.89), 0.49 (0.38, 0.63), 0.30 (0.16, 0.58), and 0.28 (0.12, 0.66), respectively (P_interaction = 0.36). Similar trends were seen in the BMI subgroups. There was a modest, not clinically meaningful, decrease (< 30%) in the median predicted exposure with increasing body weight (n = 281).

Conclusions: The findings of this post hoc analysis support the use of apixaban in patients with body weight ≥ 120 kg or BMI > 40 kg/m².

Trial registration number: NCT00643201.

Keywords: Apixaban; Body mass index; Body weight; Enoxaparin; Venous thromboembolism; Warfarin.

Fig. 1

Recurrent VTE or VTE-related death, major bleeding, and composite of major or CRNM bleeding during the treatment period by body weight category. CI confidence interval, CRNM clinically relevant non-major, NE not estimable, RR relative risk, VTE venous thromboembolism

Fig. 2

Recurrent VTE or VTE-related death, major bleeding, and composite of major or CRNM bleeding during the treatment period by BMI category. BMI body mass index, CI confidence interval, CRNM clinically relevant non-major, RR relative risk, VTE venous thromboembolism

Fig. 3

Predicted steady-state daily AUC by body weight category. Boxes indicate 25th to 75th percentiles, whiskers indicate 5th to 95th percentiles, and black horizontal lines represent the median. Numbers inside boxes are median values. Circles are individual predicted values. AUC area under the plasma concentration–time curve