Direct Oral Anticoagulants in Patients with Obesity and Atrial Fibrillation: Position Paper of Italian National Association of Hospital Cardiologists (ANMCO)

Abstract

The use of the direct oral anticoagulants dabigatran, rivaroxaban, apixaban and edoxaban (DOACs) offers some major advantages over warfarin and other vitamin K antagonists (VKAs). One advantage is the possibility to use a fixed dose in normal-weight patients, overweight patients and patients with obesity. However, the “one size fits all” strategy raised a concern regarding the possibility to undertreat patients with a high body mass index. No randomized controlled trials (RCTs) have ever compared VKAs and DOACs in this population. We analyzed data from the literature on DOAC pharmacokinetics and pharmacodynamics, results from the four pivotal phase III trials on non-valvular atrial fibrillation, retrospective observational studies and metanalyses. While we are aware of the limitation imposed by the absence of specific RCTs, we propose the position of the Italian Association of Hospital Cardiologists (ANMCO) on the use of DOACs in patients with obesity based on the existing evidence.

ANMCO (Italian Association of Hospital Cardiologists) scientific statement: obesity in adults—an approach for cardiologists

“…Although epidemiological studies have shown that the presence of obesity is associated with numerous diseases, as reported in Table 5 , for some specific diseases, a better outcome has been reported in those overweight or with first-degree obesity (BMI ≥ 30 kg/m 2 and < 35 kg/m 2 ), compared to those who had a BMI < 25 kg/m 2 [ 137 ]. Since the first identification of this counterintuitive finding, numerous similar studies have been published in different fields, such as cardiovascular diseases [ 138 ], cancer [ 139 ], diabetes [ 140 ], respiratory diseases [ 141 ] and in other clinical contexts [ 142 ]. A recent large cohort study including patients with stable coronary heart disease has found a U‐shaped relationship between BMI and cardiovascular outcomes, with the lowest cardiovascular risk in patients with a BMI of 27 kg/m 2 , which are usually classified as overweight patients [ 143 ].…”

“…The increase in epicardial fat, along with the increase in the production of inflammatory and profibrotic mediators, which have both endocrine and paracrine effects, may explain the higher risk of AF among patients with obesity [ 180 ]. Of note obesity may also affect anticoagulant drug pharmacokinetics and pharmacodynamics and in patients with severe obesity the anticoagulant treatment must be individualized [ 142 ].…”

Management of Patients Treated with Direct Oral Anticoagulants in Clinical Practice and Challenging Scenarios

“…Nevertheless, in severely obese patients, it has been postulated to consider the assessment of DOACs’ plasma levels [ 18 , 157 ]. Due to the higher reliability and the association with clinical outcomes, it is generally recommended to measure trough levels of the DOAC, although whether to evaluate the trough or peak plasma levels is currently a subject of ongoing research [ 18 ].…”

Obesity, thrombosis, venous disease, lymphatic disease, and lipedema: An obesity medicine association (OMA) clinical practice statement (CPS) 2023

“…The effects of BMI on DOAC are limited. Thus, they may be considered generally safe and effective across weight classes [ 99 ]. A systematic review and meta-analysis suggests that DOAC has similar efficacy and safety in preventing recurrent thromboembolic events in patients with severe obesity [ 100 ].…”