BACKGROUND: Atrial fibrillation (AF) and low body weight (BW, <
60 kg) are common in patients with heart failure (HF). However, the safety and effectiveness of direct oral anticoagulants (DOACs) in this group remain unclear. This study compares the efficacy and safety of apixaban versus vitamin K antagonists (VKAs) in patients with nonvalvular AF, low BW and HF. METHODS: We analysed 155,152 patients with HF and AF, weighing ≤100 kg and treated with oral anticoagulants (apixaban 86,493
VKA 68,659), from the TriNetX Global Research Network. Outcomes included ischaemic stroke/systemic embolism (SEE), clinically relevant bleedings, intracranial haemorrhage (ICH), all-cause death and net clinical benefit (composite of stroke/SEE, bleedings and all-cause death) across three BW categories: 60-100 kg (reference), 50-60 kg (low BW) and ≤50 kg (very low BW). Propensity score matching was used to balance the treatment groups. RESULTS: Patients with low BW had a higher risk of adverse events compared to those with reference BW, regardless of treatment. Apixaban consistently reduced the risk of ischaemic stroke/SEE and bleeding (including ICH) across all BW ranges (all p-interaction >
.10), and improved net clinical benefit compared to VKA (reference BW: HR .82 [95% CI: .80-.84]
low BW: HR .79 [95% CI: .74-.85]
very low BW: HR .86 [95% CI: .78-.95], p-interaction = .366). However, a significant BW-treatment interaction was observed for all-cause mortality, indicating reduced relative effectiveness of apixaban vs. VKA as BW decreases. CONCLUSION: In this large real-world analysis, treatment with apixaban was associated with a superior effectiveness and safety profile compared to VKA in patients with AF, HF and low BW. These results remained consistent, albeit slightly attenuated, in patients with very low BW. These findings provide preliminary evidence supporting the use of apixaban in this high-risk population.