ASSOCIATION OF MUSCLE MASS WITH DIRECT ORAL ANTICOAGULANT ACTIVITY IN OLDER ADULTS

Abstract

Direct oral anticoagulants (DOACs) are increasingly used to treat older adults with atrial fibrillation (AF). While current dosing recommendations are based on total body weight, the plasma levels of these hydrophilic drugs are actually determined by lean mass. In the presence of low lean mass, DOACs are distributed less in lean tissues and more in plasma. Thus, frail patients with low muscle mass may be at risk for supratherapeutic DOAC plasma levels and bleeding complications. A prospective cohort study was conducted to determine the association between appendicular lean mass (ALM) and DOAC plasma levels in patients 65 years and above receiving rivaroxaban or apixaban for AF at the Jewish General Hospital (Montréal, Canada) between January and December 2017. ALM was measured at the point of care using a portable multi-frequency bioimpedance device, and secondarily, using a dual x-ray absorptiometry scan. DOAC levels were measured using a standardized anti-Xa assay four hours after (peak) and one hour before (trough) ingestion. The cohort consisted of 62 patients, of which 47% were female, with a mean age of 77.7 ± 6.1 years. The prescribed DOAC was apixaban 2.5 mg in 21%, apixaban 5 mg in 53%, and rivaroxaban 20 mg in 25%. Overall, 25% and 16% of patients had supratherapeutic DOAC levels at peak and trough, respectively. Lower ALM was found to be an independent predictor of supratherapeutic DOAC levels at trough (OR 0.78, 95% CI 0.62 to 0.98) and peak (OR 0.84, 95% CI 0.73 to 0.99). Addition of ALM to a logistic regression model consisting of age, total body weight, and renal function resulted in improved discrimination for supratherapeutic DOAC levels at trough (C-statistic 0.88) and peak (C-statistic 0.76). When used in place of ALM, the SARC-F questionnaire for sarcopenia was similarly found to be an independent predictor of supratherapuetic DOAC levels. Our proof-of-concept study has identified an association between sarcopenia and DOAC levels in older adults with AF. Further research is needed to determine the impact of ALM on bleeding complications and the potential role of ALM-guided dosing for frail patients.View Large Image Figure ViewerDownload Hi-res image Download (PPT)