Evaluation of the Incremental Healthcare Economic Burden of Patients with Atrial Fibrillation Treated with Direct-Acting Oral Anticoagulants and Hospitalized for Major Bleeds in the USA

Adv Ther. 2020 Sep;37(9):3942-3953. doi: 10.1007/s12325-020-01440-9. Epub 2020 Jul 22.


Introduction: Direct-acting oral anticoagulants (DOACs) are associated with risk of major bleeding. This study evaluated the incremental healthcare economic burden of patients with atrial fibrillation (AF) treated with DOACs and hospitalized with a major bleed (MB).

Methods: Adult patients with AF treated with DOACs and hospitalized with MB or no MB hospitalizations during January 1, 2015-April 30, 2018 were extracted from MarketScan claims databases. The index date was defined as the first MB hospitalization for patients with MB and a random date during DOAC usage for patients without MB. Healthcare resource utilization and costs were evaluated for index hospitalizations of patients with MB and during the 6-month period prior to index dates and a variable follow-up period of 1-12 months for both patients with and those without MB. Multivariable regression analyses were performed to evaluate the incremental burden of MB vs. non-MB status on all-cause hospital days and healthcare costs.

Results: Of the overall AF patient population using DOACs (N = 152,305), 7577 (5.0%) had a hospitalization for MB. Greater proportions of those who had an MB hospitalization were older and female compared to patients without MB (mean age 76.1 vs. 70.1 years; 44.1% vs. 40.5% female, respectively). For index MB hospitalizations, mean length of stay (LOS) was 5.3 days and cost was $32,938. In adjusted analyses, patients with MB had 3.6 more hospital days, $10,609 higher inpatient cost, $9613 higher outpatient medical cost, and $18,910 higher total healthcare costs for all causes per patient during follow-up (all p < 0.001). Including index MB hospitalization costs in the follow-up, all-cause total adjusted healthcare costs were almost two times higher for patients with vs. without MB ($96,590 vs. $49,091, p < 0.001).

Conclusions: Among a large US nationally representative sample of patients with AF treated with DOACs, the cost of MB hospitalization was substantial. Furthermore, healthcare costs following MB events were nearly 40% higher compared to those of patients with AF without an MB.

Keywords: Atrial fibrillation; Direct-acting oral anticoagulants; Factor Xa inhibitors; Healthcare costs; Healthcare resource utilization; Major bleed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anticoagulants / economics*
  • Anticoagulants / therapeutic use*
  • Atrial Fibrillation / drug therapy*
  • Atrial Fibrillation / economics*
  • Atrial Fibrillation / epidemiology
  • Factor Xa Inhibitors / economics*
  • Factor Xa Inhibitors / therapeutic use*
  • Female
  • Health Care Costs / statistics & numerical data*
  • Hemorrhage / chemically induced
  • Hospitalization / economics
  • Hospitalization / statistics & numerical data
  • Humans
  • Male
  • Middle Aged
  • Patient Acceptance of Health Care / statistics & numerical data
  • Retrospective Studies
  • United States / epidemiology
  • Young Adult


  • Anticoagulants
  • Factor Xa Inhibitors