Clinical outcomes and predictors of a gap in direct-acting oral anticoagulant therapy in the elderly: A time-varying analysis of a nationwide cohort study

Thromb Res. 2023 Jun:226:61-68. doi: 10.1016/j.thromres.2023.04.018. Epub 2023 Apr 25.


Introduction: As direct-acting oral anticoagulants (DOACs) have short half-lives of around 12 h, even a short gap in DOAC therapy may diminish anticoagulation effects, increasing risks of adverse clinical outcomes. We aimed to evaluate clinical consequences of a gap in DOAC therapy with atrial fibrillation (AF) and to identify its potential predictors.

Materials and methods: In this retrospective cohort study, we included DOAC users aged over 65 years with AF from the 2018 Korean nationwide claims database. We defined a gap in DOAC therapy as no claim for a DOAC one or more days after the due date of a refill prescription. We used a time-varying-analysis method. The primary outcome was a composite of death and thrombotic events including ischemic stroke/transient ischemic attack or systemic embolism. Potential predictors of a gap included sociodemographic and clinical factors.

Results and conclusions: Among 11,042 DOAC users, 4857 (44.0 %) patients had at least one gap. Standard national health insurance, non-metropolitan locations of medical institutions, history of liver disease, chronic obstructive pulmonary disease, cancer, or dementia, and use of diuretics or non-oral agents were associated with increased risks of a gap. In contrast, history of hypertension, ischemic heart disease, or dyslipidemia were associated with a decreased risk of a gap. A short gap in DOAC therapy was significantly associated with a higher risk of the primary outcome compared to no gap (hazard ratio 4.04, 95 % confidence interval 2.95-5.52). The predictors could be utilized to identify at-risk patients to provide additional support to prevent a gap.

Keywords: Atrial fibrillation; Direct-acting oral anticoagulants; Elderly; Ischemic stroke; Thrombosis.

MeSH terms

  • Administration, Oral
  • Aged
  • Anticoagulants / therapeutic use
  • Atrial Fibrillation* / complications
  • Atrial Fibrillation* / drug therapy
  • Cohort Studies
  • Factor Xa Inhibitors / therapeutic use
  • Humans
  • Retrospective Studies
  • Stroke* / drug therapy
  • Stroke* / etiology
  • Stroke* / prevention & control
  • Warfarin / therapeutic use


  • Warfarin
  • Anticoagulants
  • Factor Xa Inhibitors