Impact of body mass index on real-world outcomes of rivaroxaban treatment in Japanese patients with non-valvular atrial fibrillation

Abstract

This sub-analysis of the XAPASS, a prospective, single-arm, observational study, aimed to evaluate relationships between body mass index (BMI) and safety (major bleeding and all-cause mortality) and effectiveness [stroke/non-central nervous system (non-CNS) systemic embolism (SE)/myocardial infarction (MI)] outcomes in Japanese patients with non-valvular atrial fibrillation (NVAF) receiving rivaroxaban. Patients were categorized according to BMI (kg/m 2 ) as underweight (< 18.5), normal weight (18.5 to < 25), overweight (25 to < 30), or obese (≥ 30). In total, 9578 patients with NVAF completed the 1-year follow-up and were evaluated; of these, 7618 patients had baseline BMI data. Overall, 542 (5.7%), 4410 (46.0%), 2167 (22.6%), and 499 (5.2%) patients were underweight, normal weight, overweight, and obese, respectively. Multivariable Cox regression analysis demonstrated that none of the BMI categories were independent predictors of major bleeding whereas being underweight was independently associated with increased all-cause mortality [hazard ratio (HR) 3.56, 95% confidence interval (CI) 2.40-5.26, p < 0.001]. The incidence of stroke/non-CNS SE/MI was higher in patients who were underweight than in those of normal weight (HR 2.11, 95% CI 1.20-3.70, p = 0.009). However, in multivariable analyses, being underweight was not identified as an independent predictor of stroke/non-CNS SE/MI (HR 1.64, 95% CI 0.90-2.99, p = 0.104). In conclusion, the high incidence of thromboembolic events and all-cause mortality in patients who were underweight highlights that thorough evaluation of disease status and comorbidities may be required in this population.

The impact of underweight and obesity on outcomes in anticoagulated patients with atrial fibrillation: A systematic review and meta‐analysis on the obesity paradox

“…Also, the use of antiplatelets cannot (fully) explain these heterogeneous safety results, as 33.2% of morbidly obese patients in the ENGAGE AF‐TIMI 48 trial 9 and 33.1% of obese patients in the ARISTOTLE trial 8 used antiplatelets. Lastly, substantial heterogeneity in the risks of mortality and major bleeding was detected in underweight AF patients (I 2 81% and 80%, respectively), probably due to heterogeneous results of the included observational studies 16,22,24 . Indeed, after one‐by‐one exclusion of these studies, results remained the same, but heterogeneity was generally lower (eFigure 5,6).…”

“…Results on AF‐related outcomes in anticoagulated AF patients categorized according to their BMI from four (post hoc analyses of) Phase III RCTs 7‐9,12 and five longitudinal observational cohort studies 16,19,22‐24 were pooled in a meta‐analysis. However, as only one study 16 provided data on the gastrointestinal bleeding risk, this outcome could not be included in the meta‐analysis.…”

“…In line with the impact on the thromboembolic risk, (morbid) obesity was associated with significantly lower all-cause mortality risks compared to the normal BMI subgroup in the ARISTOTLE 8 and ENGAGE AF-TIMI 48 trial, 9 whereas significantly higher mortality risks were demonstrated in underweight AF patients 9 (eTable 2). Likewise, significantly lower mortality risks 4,16,20,29,30 in overweight or obese and significantly higher risks 16,20,22,24,30 in underweight AF patients were observed in most observational studies. However, in some observational studies, no impact of increasing BMI on the mortality risk was observed.…”

“…Fifth, endpoints frequently differed from our outcomes of interest, as some studies 14,16‐18,24,28,32,33 examined the risk of ischemic stroke, stroke/SE/mortality, stroke/SE/myocardial infarction, or any (major or minor) bleeding. Lastly, results from observational studies 16‐18,20,22,24,30,33 on AF‐related outcomes in underweight versus normal BMI AF patients were all performed in an Asian setting potentially limiting generalizability. Similarly, morbidly obese AF patients were more likely to be of Caucasian ethnicity (especially from North America) 8,9 .…”

“…18 However, in other observational studies, the impact of BMI on AFrelated outcomes was not or less clear, illustrating the general controversy regarding the topic. For example, obesity was associated with similar stroke, 19 stroke/SE, 4,[20][21][22][23] stroke/SE/myocardial infarction, 24 or stroke/ SE/venous thromboembolism 25,26 risks compared to normal BMI AF patients included in the FANTASIIA registry 19 ; ORBIT-AF registry (69%-75% VKA-treated) 4 ; J-RHYTHM registry (86%-91% VKA-treated) 20 ; Danish Diet, Cancer and Health study (19%-24% VKA-treated) 21 ; XAPASS study 24 ; PREFER in AF (PROLONGATION) registries 26 ; the Korean retrospective cohort study by Park et al 22 ; and two U.S. retrospective cohort studies by Kaplan et al 23 and Netley et al 25 Similarly, no significant differences in the risk of ischemic stroke, 16 stroke/SE, 20,22 or stroke/SE/myocardial infarction 24 could be demonstrated in underweight versus normal BMI AF patients in two Korean studies by Lee et al 16 and Park et al, 22 the J-RHYTHM registry 20 and the XAPASS study. 24 In contrast, two observational studies illustrated worse outcomes in obese AF patients.…”