Comparative Effectiveness and Safety of Direct Oral Anticoagulants vs Warfarin Among Obese Patients With Atrial Fibrillation

Laurie-Anne Boivin-Proulx,Brian J Potter,Marc Dorais,Sylvie Perreault

doi:10.1016/j.cjco.2022.01.002

Abstract

BackgroundObese patients are underrepresented in clinical trials assessing the comparative effectiveness and safety of use of direct oral anticoagulants vs use in atrial fibrillation (AF) patients. MethodsUsing data from Quebec provincial administrative databases, for the years2010-2017, we created a retrospective cohort of patients with inpatient or outpatient coding for AF and obesity who were newly prescribed an oral anticoagulant. The primary safety outcome was a composite of intracranial, gastrointestinal, and major bleeding from other sites, and the primary effectiveness outcome was a composite of ischemic stroke, systemic embolism, acute myocardial infarction, and death in the first year after oral anticoagulant initiation. Treatment groups were compared using inverse-probability-of-treatment-weighting Cox proportional-hazards models. ResultsA total of 2263 patients were included, of whom 1253, 403, and 539 filled a warfarin, standard-dose rivaroxaban, and standard-dose apixaban prescription, respectively. Standard-dose rivaroxaban was associated with a similar composite safety (hazard ratio [HR] 0.91; 95% confidence interval [CI] 0.44-1.91) and composite effectiveness risk (HR 1.42; 95% CI 0.99-2.04) compared to warfarin, whereas standard-dose apixaban was associated with a lower composite safety (HR 0.40; 95% CI 0.16-0.98) and similar composite effectiveness risk (HR 0.96; 95% CI 0.67-1.39). ConclusionUse of direct oral anticoagulants in obese AF patients was associated with a similar effectiveness and safety profile to that of warfarin use.

Highlights

Obesity is an independent risk factor for atrial fibrillation (AF), with a 10-29%excess risk of incident AF for every 5-unit increase in body mass index (BMI).(1)somewhat paradoxically, BMI is independently associated with a lower risk of stroke/systemic embolism (SE) and a higher bleeding risk.[2, 3] As such, the risk-benefit threshold for oral anticoagulant (OAC) prescription may not occurJournal Pre-proof at the same point in obese and non-obese patients
direct oral anticoagulants (DOACs) in obese AF patients were associated with a similar effectiveness and safety profile compared to warfarin
We found that DOACs in obese AF patients have a similar effectiveness and safety profile compared to warfarin

Summary

Introduction

Journal Pre-proof at the same point in obese and non-obese patients This clinical conundrum is further compounded by both a lack of robust pharmacokinetic data to guide the use of direct oral anticoagulants (DOACs) in patients with extreme BMIs and a paucity of clinical data to support DOAC prescription in obese populations.[4]. In 2016, an obesity subgroup analysis of phase 3 clinical trial data on DOACs was conducted by the Scientific and Standardization Committee (SCC) of the International Society of Thrombosis and Haemostasis (ISTH) to look at the efficacy and safety of DOACs in obese patients.[4] The committee concluded that DOACs are safe and effective, but only up to a BMI ≤ 40 kg/m2 or body weight ≤ 120 kg.[4] Citing very limited data regarding DOAC use in severe obesity Obese patients are underrepresented in clinical trials assessing the comparative effectiveness and safety of direct oral anticoagulants (DOACs) vs in atrial fibrillation (AF) patients

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Findings

Discussion

Conclusion