Apixaban Use in Obese Patients: A Review of the Pharmacokinetic, Interventional, and Observational Study Data

Abstract

Relatively little is known about the influence of extreme body weight on the pharmacokinetics (PK), pharmacodynamics (PD), efficacy, and safety of drugs used in many disease states. While direct oral anticoagulants (DOACs) have an advantage over warfarin in that they do not require routine drug monitoring, some may regard this convenience as less compelling in obese patients. Some consensus guidelines discourage using DOACs in patients weighing > 120 kg or with a body mass index > 35–40 kg/m 2 , given a sparsity of available data in this population and the concern that fixed dosing in obese patients might lead to decreased drug exposure and lower efficacy. Per the prescribing information, apixaban does not require dose adjustment in patients weighing above a certain threshold (e.g., ≥ 120 kg). Data from healthy volunteers and patients with nonvalvular atrial fibrillation (NVAF) or venous thromboembolism (VTE) have shown that increased body weight has a modest effect on apixaban’s PK. However, the paucity of exposure data in individuals > 120 kg and the lack of guideline consensus on DOAC use in obese patients continue to raise concerns about potential decreased drug exposure at extreme weight. This article is the first to comprehensively review the available PK data in obese individuals without NVAF or VTE, and PK, PD, efficacy, effectiveness, and safety data for apixaban in obese patients with either NVAF or VTE, including subgroup analyses across randomized controlled trials and observational (real-world) studies. These data suggest that obesity does not substantially influence the efficacy, effectiveness, or safety of apixaban in these patients. Trial Registration ARISTOTLE: NCT00412984; AVERROES: NCT00496769; AMPLIFY: NCT00643201; AMPLIFY-EXT: NCT00633893; ADVANCE-1: NCT00371683; ADVANCE-2: NCT00452530; ADVANCE-3: NCT00423319 Video abstract Supplementary Information The online version contains supplementary material available at 10.1007/s40256-022-00524-x.

Direct oral anticoagulants and the risk of adverse clinical outcomes among patients with different body weight categories: a large hospital-based study

“…Specifically, other observational studies and randomised controlled trials (RCTs) widely suggest that increased BMI in VTE/NVAF has no significant effect on the safety and efficacy of apixaban. In other words, despite exposure being slightly reduced, no dose adjustment was required [20]. However, this does not dismiss the claim that the morbidly obese category had the most incidence of thrombotic events among the BMI classes [8,9,21,22].…”

Platelet-rich fibrin ensures hemostasis after single-tooth removal under factor Xa inhibitors — a clinical prospective randomized split-mouth study

“…Patients are primarily older than 65, with decreased renal function and other comorbidities [ 13 , 14 ]. Nevertheless, recent studies suggested that age, gender, and obesity do not have a clinically relevant effect on the pharmacokinetics and pharmacodynamics of FXa inhibitors [ 15 , 16 ]. Furthermore, the influence of renal function on clearance of FXa inhibitors is moderate [ 17 , 18 ], even in subjects with severe renal impairment (creatinine clearance < 30 mL/min) [ 19 ].…”

Practices, beliefs, and attitudes of clinicians in prescribing direct oral anticoagulants for obese adults with atrial fibrillation: a qualitative study

“…Furthermore, there is disagreement in pharmacokinetic reports of DOAC peak and trough plasma concentrations when comparing normal and obese adults [17][18][19][20]. This disagreement pervades opinion regarding the clinical effect of obesity in the context of DOACs, given the lack of longterm outcome data and variability in prescribing [21,22].…”