Effectiveness and Safety of Anticoagulation Therapy in Frail Patients With Atrial Fibrillation

Stroke. 2022 Jun;53(6):1873-1882. doi: 10.1161/STROKEAHA.121.036757. Epub 2022 Feb 3.


Background: Frail patients with atrial fibrillation (AF) are less likely to receive anticoagulation than nonfrail patients with AF despite frailty being associated with poorer clinical outcomes including stroke. Using a population-based cohort, we sought to assess the effectiveness and safety of oral anticoagulants (OACs) in frail patients with AF.

Methods: This retrospective cohort study analyzed 83 635 patients aged at least 65 years with AF and frailty (≥5 Hospital Frailty Risk Score) between January 1, 2013 and December 31, 2016 from the Korean National Health Insurance Service database. To account for the differences between patients receiving OAC or not and across different OAC regimens, propensity score-weighting was used. Net adverse clinical event, defined as the first event of ischemic stroke, major bleeding, or cardiovascular death, was compared. In addition, each individual outcome was examined separately.

Results: In the study population (57.1% women; mean age, 78.5±7.2 years), a total of 14 968 net adverse clinical event, 3718 ischemic stroke, 5536 major bleeding, and 6188 cardiovascular death occurred. In comparison with no OAC use, OAC use was associated with lower risks of net adverse clinical event (hazard ratio, 0.78 [95% CI, 0.75-0.82]), ischemic stroke (hazard ratio, 0.91 [95% CI, 0.86-0.97]), and cardiovascular death (hazard ratio, 0.52 [95% CI, 0.49-0.55]), but no difference was observed for major bleeding (hazard ratio, 1.02 [95% CI, 0.95-1.10]). Compared with warfarin, all four individual direct OAC were associated with decreased risks of net adverse clinical event, ischemic stroke, major bleeding, and cardiovascular death. The associations for OAC use (compared to no OAC use) or direct OAC use (compared to warfarin) with favorable outcomes were more prominent in individuals with a higher CHA2DS2-VASc score of at least 3.

Conclusions: Among frail patients with AF, OAC treatment was associated with a positive net clinical outcome. Direct OACs provided lower incidences of stroke, bleeding, and mortality, compared with warfarin.

Keywords: Editorials; anticoagulant; atrial fibrillation; frailty; ischemic stroke; mortality.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aged
  • Aged, 80 and over
  • Anticoagulants / adverse effects
  • Atrial Fibrillation* / complications
  • Atrial Fibrillation* / drug therapy
  • Atrial Fibrillation* / epidemiology
  • Female
  • Frail Elderly
  • Frailty* / chemically induced
  • Frailty* / complications
  • Frailty* / drug therapy
  • Hemorrhage / chemically induced
  • Hemorrhage / complications
  • Hemorrhage / epidemiology
  • Humans
  • Ischemic Stroke*
  • Male
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Stroke* / drug therapy
  • Warfarin / adverse effects


  • Anticoagulants
  • Warfarin