Required warfarin dose and time in therapeutic range in patients with diagnosed Nonalcoholic Fatty Liver Disease (NAFLD) or Nonalcoholic Steatohepatitis (NASH)

PLoS One. 2021 Sep 15;16(9):e0251665. doi: 10.1371/journal.pone.0251665. eCollection 2021.

Abstract

Warfarin has been widely used to treat thromboembolism. The effect of nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH), on warfarin dosing remains unknown. This study aims to examine the effects of NAFLD/NASH on the average daily dose (ADD) of warfarin and the time in therapeutic range (TTR). This is a retrospective study utilizing an administrative data. We included patients with at least 2 months of warfarin dispensing and two subsequent consecutive INR measures. The ADD of warfarin to achieve therapeutic range INR levels, and TTR were compared between patients with and without NAFLD/NASH in four subgroups of patients accounting for the presence of obesity and diabetes. Generalized linear models (GLM) with Propensity score (PS) fine stratification were applied to evaluate the relative differences (RD) of warfarin ADD and TTR (>60%) in four subgroups. A total of 430 NAFLD/NASH patients and 38,887 patients without NAFLD/NASH were included. The ADD and TTR, were not significant in the overall cohort between those with and without NAFLD/NASH. However, GLM results in patients without diabetes or obesity (N = 26,685) showed a significantly lower warfarin ADD (RD: -0.38; 95%CI: -0.74--0.02) and shorter TTR (OR: 0.71; 95%CI: 0.52-0.97) in patients diagnosed with NAFLD/NASH. The effects of NAFLD/NASH on warfarin dose or TTR were observed in patients without obesity and diabetes. Obesity and diabetes appear to be significant modifiers for the effects of NAFLD/NASH on warfarin dose and TTR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anticoagulants / administration & dosage*
  • Anticoagulants / therapeutic use
  • Drug Dosage Calculations
  • Female
  • Humans
  • Linear Models
  • Male
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease / diagnosis*
  • Propensity Score
  • Retrospective Studies
  • Time Factors
  • Warfarin / administration & dosage*
  • Warfarin / therapeutic use

Substances

  • Anticoagulants
  • Warfarin

Grants and funding

This study was supported by an internal funding from the CVS Health through University of Rhode Island, College of Pharmacy Healthcare Research Operating Fund program.Xuerong Wen, Shuang Wang, Fetameh Akhlaghi received summer salaries from this internal grant in the summer of 2019. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.