LAUSR

Although nonvitamin K antagonist oral anticoagulants (NOACs) have generally shown comparable efficacy and better safety compared with warfarin, atrial fibrillation (AF) patients with extreme body weights have been underrepresented in pivotal clinical trials. Low-body-weight (LBW) patients with AF usually have other comorbidities, resulting in higher risks of major bleeding and mortality. A consensus statement from the European Society of CardiologyWorking Group on Thrombosis recommended that edoxaban dose be halved (30mg once daily) in patients with LBW ( 60 kg) and apixaban dose be halved (2.5mg twice daily) if LBW is combined with renal impairment or old age.1 Rivaroxaban did not show clinically relevant changes in plasma concentration in patients weighing <50 kg and does not require dose reduction according to bodyweight. Of note, dabigatran data in patients with extreme LBW (below 50 kg) are limited. In general, however, there are still limited data on whether fixed-dose NOACs could be safely and effectively prescribed in patients with extreme body weights. Asian patients with AF have generally shown poor quality of warfarin control and a higher risk of intracranial hemorrhage (ICH) with warfarin use. Subsequently, NOACs were introduced, and these patients showed similar or better results with NOACs compared with warfarin in a metaanalysis ofmajor pivotal trials.2However, LBWposes another challenge for stroke prevention in Asian patients with AF. AF patients with LBW are more prevalent in the Asian population. In the pivotal trials, the mean body weight of Asian patients with AF was lower than that of non-Asian patients (►Table 1). Recently, we reported the effectiveness and safety of NOACs in Korean AF patientswith LBW ( 60 kg) who were on oral anticoagulants (n1⁄4 14,013 with NOACs and n1⁄4 7,576 with warfarin).3 NOACs were associated with lower risks of both stroke and major bleeding than warfarin in patients with LBW ( 60 kg) and extreme LBW (<50 kg). Furthermore, on-label dosing of NOACs showed the largest risk reduction for the clinical outcomes compared with that of warfarin, whereas off-label overdosing showed similar outcomes as warfarin. Therefore, label adherence to NOACs, especially avoiding off-label overdosing, is important for AF patients with LBW. Another challenge in Asian patients with AF is that the safety zone of NOACs is narrower than that in non-Asians.4 In the Asian population, for example, the risks of ICH and major bleeding increased steeply as the concentration of edoxaban increased, whereas in non-Asians, the risk of ICH did not increase steeply. Considering the high prevalence of LBWand narrow safety zone of NOACs in Asian patients with AF, more evidence regarding the safety and optimal dosing of NOACs in AF patients with LBW is needed. Patients with obesity are known to have better cardiovascular outcomes, a phenomenon known as the “obesity paradox.” Similarly, NOAC trials have shown that obese patients with AF have lower risks of stroke and major bleeding.5 In line with previous studies, Boriani et al reported that a higher body mass index was associated with a lower risk of stroke/systemic embolic events (SEEs), whereas patientswho are underweight (<18.5 kg/m)would partially be analyzed due to a limited number.6 In this issue of Thrombosis and Haemostasis, Boriani et al reported the efficacy and safety of edoxaban versus warfarin in AF patients with extreme body weights.7 They selected patients from the ENGAGE AF-TIMI 48 trial and categorized them into low, middle, and high body-weight groups as 5th percentile (LBW, 55 kg), 45th to 55th percentile (MBW, 80–84 kg), and 95th percentile (HBW, 120 kg). Not surprisingly, the LBW group comprised frail individuals: they were older and more likely to be women, had higher prevalence of renal impairment and higher CHADS2 and HAS-BLED scores, and had a higher risk of falling than the MBWor HBWgroup. Furthermore, the LBW group had the lowest baseline