Fat-free mass index and apixaban exposure in frail hospitalized older adults: An exploratory study

Background Reduced muscle mass may influence creatinine-based renal estimates and direct oral anticoagulant exposure in frail older adults. Objectives To explore the relationship between fat-free mass index (FFMI) and apixaban trough concentrations in hospitalized older adults. Methods In this retrospective study, FFMI was assessed by bioelectrical impedance analysis in patients aged ≥75 years treated with apixaban. FFMI was considered a body-composition marker, not a diagnostic criterion for sarcopenia. Results Among 305 screened patients, 43 receiving apixaban 5 mg twice daily with compliant trough sampling were included. Mean age was 83.6 ± 5.8 years. FFMI correlated inversely with apixaban concentrations in the unadjusted analysis (Spearman’s ρ = −0.34, p = 0.024). In univariable linear regression, lower FFMI was associated with higher apixaban concentrations (β = −8.64 ng/mL per kg/m², 95% CI −16.15 to −1.13; p = 0.025), but this association was not confirmed after adjustment for sex and serum creatinine (adjusted β = −6.77, 95% CI −15.20 to 1.65; p = 0.112) or in the sensitivity analysis including both dose groups ( n = 82; ρ = −0.06, p = 0.575). Body weight, BMI, and creatinine-based renal estimates were not significantly associated with apixaban concentrations. Conclusions An inverse relationship between FFMI and apixaban trough concentrations was observed in the unadjusted primary analysis but was not confirmed after multivariable adjustment or in the sensitivity analysis. This preliminary signal should be considered hypothesis-generating and requires confirmation in larger prospective studies.