Bleeding related to oral anticoagulants: Trends in US emergency department visits, 2016-2020

Abstract

Background: Clinical trials suggest lower rates of major bleeding with direct-acting oral anticoagulants (DOACs) than with warfarin, but anticoagulant-related bleeding remains one of the most common outpatient adverse drug events.

Methods: We estimated the number of emergency department (ED) visits and subsequent hospitalizations for oral anticoagulant-related bleeding in 2016-2020 based on active surveillance in a nationally representative, size-stratified probability sample of 60 U.S. hospitals. We estimated rates of ED visits using a nationally-projected retail prescription dispensing database.

Results: Based on 19,557 cases, oral anticoagulant-related bleeding resulted in an estimated 1,270,259 (95 % Confidence Interval [CI], 644,686-1,895,832) ED visits for the five years 2016-2020, of which 47.8 % (95 % CI, 40.6 %-55.0 %) resulted in hospitalization. Oral anticoagulant-related bleeding resulted in an estimated 230,163 (95% CI, 109,598-350,728) ED visits in 2016 and 301,433 (95% CI, 138,363-464,503) in 2020. During 2016-2020, ED visits for DOAC-related bleeding increased by an average of 27.9 % (95 % CI, 24.0 %-32.0 %; p < .001) per year, while ED visits for warfarin-related bleeding decreased by an average of 8.8 % (95 % CI, -10.7 % to -7.0 %; p = .001) per year. The estimated rate of bleeding visits per 100 patients dispensed oral anticoagulants at least once in 2016-2020 was highest for patients aged ≥ 80 years (13.1; 95 % CI, 6.2-20.0) and lowest for those aged <45 years (4.0; 95 % CI, 2.6-5.5); it was 5.9 visits per 100 patients dispensed DOACs [95 % CI, 2.5-9.2] and 13.0 visits per 100 patients dispensed warfarin [95 % CI, 7.4-18.7].

Conclusions: Although the rates of ED visits for anticoagulant-related bleeding may be lower for DOACs than for warfarin, persistently large numbers of patients requiring ED visits for anticoagulant-related bleeding despite increased use of DOACs and declining use of warfarin suggest that efforts to improve appropriate prescribing and monitoring of anticoagulants remain important.

Keywords: Adverse drug events; Anticoagulant-related bleeding; Oral anticoagulants; Pharmaceutical safety; Public health surveillance.

Figure 1.

National estimates of Emergency Department (ED) visits for Oral Anticoagulant-related Bleeding and Patients Dispensed Oral Anticoagulants, by Year—United States, 2016–2020. Estimates of ED visits for oral anticoagulant-related bleeding are from the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project, CDC; estimates of unique recipients of dispensed oral anticoagulants (direct-acting oral anticoagulants [DOACs] or warfarin) from outpatient retail pharmacies are from IQVIA Total Patient Tracker (2016–2020). Error bars display 95% confidence intervals for ED visit estimates. Top panel: national estimates of ED visits for oral anticoagulant-related bleeding (solid line and primary vertical axis) and unique recipients of dispensed oral anticoagulants (dashed line and secondary vertical axis). Middle panel: national estimates of ED visits for DOAC-related bleeding (solid line and primary vertical axis) and unique recipients of dispensed DOAC prescriptions (dashed line and secondary vertical axis). Bottom panel: national estimates of ED visits for warfarin-related bleeding (solid line and primary vertical axis) and unique recipients of dispensed warfarin prescriptions (dashed line and secondary vertical axis). Note: coefficient of variation for the 2016 DOAC-related bleeding estimate exceeds 30% and may therefore be considered statistically unstable.