Non-vitamin K antagonist oral anticoagulants (NOACs) versus vitamin K antagonists (VKAs) in (morbidly) obese or low body weight patients with atrial fibrillation: a meta-analysis

Abstract

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Fund for Scientific Research Flanders (FWO) Background Oral anticoagulants are crucial for preventing systemic thromboembolism in atrial fibrillation (AF), with guidelines preferring non-vitamin K antagonist oral anticoagulants (NOACs) over vitamin K antagonists (VKAs) in the general AF population. However, as NOACs are administered in fixed doses, concerns of unintentional underdosing in morbidly obese patients and unintentional overdosing in underweight patients have emerged. Moreover, VKAs are still recommended in morbidly obese patients (body mass index (BMI) ≥40 kg/m², body weight >120 kg) due to lack of data for NOACs in these patients. Purpose A critical appraisal of the benefit-risk profile of NOACs in AF patients across the body weight spectrum.  Methods After searching the Medline database, phase III randomized controlled trials (RCTs) and longitudinal observational cohort studies on the effectiveness and safety of NOACs versus VKAs in obese (BMI ≥30 kg/m²), and class III obese (BMI ≥40 kg/m²) non-valvular AF patients, and in low body weight (≤60 kg) AF patients during a mean/median follow-up of ≥6 months were included. The meta-analyses were performed using a random effects model with the Mantel-Haenszel method. Results A meta-analysis based on 4 phase III RCTS and 3 longitudinal observational cohort studies demonstrated that NOAC use in obese and class III obese AF patients was associated with significantly lower stroke/systemic embolism (stroke/SE) risks (RR 0.82, 95%CI [0.71-0.96]; and RR 0.75, 95%CI [0.64-0.87], respectively), similar to lower major bleeding risks (RR 0.83, 95%CI [0.69-1.00]; and RR 0.74, 95%CI [0.57-0.95], respectively), and similar mortality risks (RR 0.92, 95%CI [0.73-1.15]; and RR 1.17, 95%CI [0.83-1.64], respectively) as compared to VKAs. In AF patients ≤60 kg, significantly lower stroke/SE (RR 0.63, 95%CI [0.56-0.71]) and major bleeding risks (RR 0.71, 95%CI [0.62-0.80]), and similar mortality risks (RR 0.68, 95%CI [0.42-1.10]) were observed for NOAC- versus VKA-treated patients in a meta-analysis based on 4 phase III RCTs and 2 longitudinal observational cohort studies. Conclusions The benefit-risk profile of NOACs seems preserved in (morbidly) obese AF patients and patients with low body weight of ≤60 kg. However, more data are needed in underweight AF patients (BMI <18.5 kg/m²) and on differences between NOACs to further optimize management in these patient subgroups.