Concomitant use of direct oral anticoagulants and aspirin versus direct oral anticoagulants alone in atrial fibrillation and flutter: a retrospective cohort

BMC Cardiovasc Disord. 2020 Jun 1;20(1):263. doi: 10.1186/s12872-020-01509-x.


Background: The benefit of combining aspirin and direct oral anticoagulants on the reduction of cardiovascular events in atrial fibrillation or flutter is not well studied. We aimed to assess whether concurrent aspirin and direct oral anticoagulant therapy for atrial fibrillation or flutter will result in less coronary, cerebrovascular and systemic ischemic events compared to direct oral anticoagulant therapy alone.

Methods: Retrospective study of adult patients between 18 and 100 years old who have nonvalvular atrial fibrillation or flutter and were started on a direct oral anticoagulant (apixaban, rivaroxaban, or dabigatran), between January 1, 2010 and September 1, 2015 within the Beaumont Health System. Exclusions were history of venous thromboembolic disease and use of other antiplatelet therapies such as P2Y12 inhibitors. Patients were classified into two groups based on concurrent aspirin use and observed for a minimum of 2 years. Primary outcome was major adverse cardiac events, defined as acute coronary syndromes, ischemic strokes, and embolic events. Secondary outcomes were bleeding and death.

Results: Six thousand four patients were in the final analysis, 57% males and 80% Caucasians, median age 71, interquartile range (63-80). The group exposed to aspirin contained 2908 subjects, and the group unexposed to aspirin contained 3096 subjects. After using propensity scores to balance the baseline characteristics in both groups, the analysis revealed higher rate of major adverse cardiac events in the exposed group compared to the unexposed group, (HR 2.11, 95% CI (1.74-2.56)) with a number needed to harm of 11 (95% CI [9-11]). The rate of bleeding was also higher in the exposed group, (HR 1.30, 95% CI (1.11-1.52)). The rate of death was not statistically different between the groups, (HR 0.87, 95% CI (0.61-1.25)).

Conclusions: In this observational analysis of patients with atrial fibrillation and flutter, the concomitant use of direct oral anticoagulants and aspirin was associated with an increased risk of both major adverse cardiac and bleeding events when compared to the use of direct oral anticoagulants alone. These findings underscore the potential harm of this combination therapy when used without a clear indication.

Keywords: Aspirin; Atrial fibrillation; Atrial flutter; Bleeding; Direct oral anticoagulant; Harm; Major adverse cardiac events.

Publication types

  • Comparative Study
  • Observational Study

MeSH terms

  • Acute Coronary Syndrome / diagnosis
  • Acute Coronary Syndrome / mortality
  • Acute Coronary Syndrome / prevention & control*
  • Administration, Oral
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Aspirin / administration & dosage*
  • Aspirin / adverse effects
  • Atrial Fibrillation / diagnosis
  • Atrial Fibrillation / drug therapy*
  • Atrial Fibrillation / mortality
  • Atrial Flutter / diagnosis
  • Atrial Flutter / drug therapy*
  • Atrial Flutter / mortality
  • Embolism / diagnosis
  • Embolism / mortality
  • Embolism / prevention & control*
  • Factor Xa Inhibitors / administration & dosage*
  • Factor Xa Inhibitors / adverse effects
  • Female
  • Hemorrhage / chemically induced
  • Humans
  • Ischemic Stroke / diagnosis
  • Ischemic Stroke / mortality
  • Ischemic Stroke / prevention & control*
  • Male
  • Middle Aged
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Platelet Aggregation Inhibitors / adverse effects
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • Young Adult


  • Factor Xa Inhibitors
  • Platelet Aggregation Inhibitors
  • Aspirin