Approximately one-third of patients receiving direct oral anticoagulants (DOAC) for the treatment of atrial fibrillation (AF) and/or venous thromboembolic disease (VTE) also receive aspirin without a clear indication, according to the findings of study recently published in JAMA Internal Medicine.

There is limited evidence surrounding the number of AF or VTE patients receiving aspirin in addition to DOAC therapy and the effect this combination has on clinical outcomes. This registry-based cohort study aimed to assess both the frequency of prescription of concomitant aspirin (ASA) and DOAC therapy as well as its effect on clinical outcomes in patients with AF or VTE.

The study was carried out between January 2015 and December 2019 at 4 anticoagulation clinics in Michigan. Study participants included adults receiving DOAC therapy for AF or VTE without recent myocardial infarction or a history of heart valve replacement.

The main outcomes of the study included bleeding rates, thrombosis rates, emergency department visits, hospitalizations, and death. The study cohort included a total of 3280 patients. The mean (SD) age of the patients was reported to be 68.2 (13.3) years and 1673 (51.0%) were male. The study authors divided the patients into 2 propensity score–matched cohorts with 1047 patients each, and used these cohorts to compare DOAC plus ASA to DOAC only. The mean (SD) follow-up of the patients was reported to be 20.9 (19.0) months. 

Of the total patients included in the analysis, 1107 (33.8%) were receiving combination therapy without a clear indication for ASA. “Patients taking DOAC and ASA experienced more bleeding events compared with DOAC monotherapy (26.0 bleeds vs 31.6 bleeds per 100 patient years, P =.01),” the authors reported. “Specifically, patients undergoing combination therapy had significantly higher rates of nonmajor bleeding (26.1 bleeds vs 21.7 bleeds per 100 patient years, P =.02) compared with DOAC monotherapy.”

Findings revealed that the cohorts had similar rates of major bleeding. Additionally, similar rates of thrombotic events were observed, with patients receiving DOAC plus ASA therapy experiencing 2.5 events per 100 patient years compared with 2.3 events per 100 patient years for patients receiving DOAC therapy alone (P =.80). Combination therapy was also associated with higher hospitalization rate compared with DOAC monotherapy (9.1 vs 6.5 admissions per 100 patient years, respectively; P =.02).

Based on their findings, the authors concluded that the concomitant use of DOAC and aspirin in patients without recent acute coronary syndrome or a history of heart valve replacement appears to increase bleeding risk and hospitalization. They added that “Further research is needed to determine if select high-risk patient subgroups derive a net benefit from combination therapy.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Schaefer JK, Errickson J, Li Y. Adverse events associated with the addition of aspirin to direct oral anticoagulant therapy without a clear indication. [published online April 19, 2021]. JAMA Internal Medicine. doi: jamainternmed.2021.1197