Muscle Mass and Direct Oral Anticoagulant Activity in Older Adults With Atrial Fibrillation

J Am Geriatr Soc. 2021 Apr;69(4):1012-1018. doi: 10.1111/jgs.16992. Epub 2021 Jan 11.

Abstract

Background: Direct oral anticoagulants (DOAC) are hydrophilic drugs with plasma levels inversely proportional to lean body mass. Sarcopenic patients with low muscle mass may be at risk for supra-therapeutic DOAC levels and bleeding complications. We therefore sought to examine the influence of lean body mass on DOAC levels in older adults with atrial fibrillation (AF).

Methods: A prospective cohort study was conducted with patients 65 years of age or more receiving rivaroxaban or apixaban for AF. Appendicular lean mass (ALM) was measured using a bioimpedance device and a dual X-ray absorptiometry scanner. DOAC levels were measured using a standardized anti-Xa assay 4 hours after (peak) and 1 hour before (trough) ingestion.

Results: The cohort consisted of 62 patients (47% female, 77.0 ± 6.1 years). The prescribed DOACs were apixaban 2.5 mg (21%), apixaban 5 mg (53%), and rivaroxaban 20 mg (26%). Overall, 16% had supra-therapeutic DOAC levels at trough and 25% at peak. In the multivariable logistic regression model, lower ALM was independently associated with supra-therapeutic DOAC levels at trough (odds ratio per ↓ 1-kg 1.23, 95% confidence interval 1.02 to 1.49) and peak (odds ratio per ↓ 1-kg 1.18, 95% confidence interval 1.02 to 1.37). Addition of ALM to a model consisting of age, total body weight, and renal function resulted in improved discrimination for supra-therapeutic DOAC levels.

Conclusion: Our proof-of-concept study has identified an association between ALM 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 sarcopenic patients.

Keywords: anticoagulation; atrial fibrillation; frailty; pharmacokinetics; sarcopenia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorptiometry, Photon / methods
  • Aged
  • Atrial Fibrillation* / blood
  • Atrial Fibrillation* / drug therapy
  • Blood Coagulation Tests
  • Body Mass Index
  • Drug Dosage Calculations
  • Drug Monitoring / methods*
  • Electric Impedance
  • Factor Xa Inhibitors / administration & dosage
  • Factor Xa Inhibitors / adverse effects
  • Factor Xa Inhibitors / pharmacokinetics
  • Female
  • Hemorrhage* / chemically induced
  • Hemorrhage* / prevention & control
  • Humans
  • Kidney Function Tests / methods
  • Male
  • Proof of Concept Study
  • Pyrazoles* / administration & dosage
  • Pyrazoles* / adverse effects
  • Pyrazoles* / pharmacokinetics
  • Pyridones* / administration & dosage
  • Pyridones* / adverse effects
  • Pyridones* / pharmacokinetics
  • Rivaroxaban* / administration & dosage
  • Rivaroxaban* / adverse effects
  • Rivaroxaban* / pharmacokinetics
  • Sarcopenia / blood
  • Sarcopenia / diagnosis
  • Stroke* / etiology
  • Stroke* / prevention & control
  • Thinness / diagnosis

Substances

  • Factor Xa Inhibitors
  • Pyrazoles
  • Pyridones
  • apixaban
  • Rivaroxaban

Grants and funding