Risks of concomitant aspirin therapy with oral anticoagulation in patients with atrial fibrillation

orbit AF substudy visual abstract on use of aspirin versus OAC in patients with atrial fibrillation

Summarized by: Usama bin Nasir, MD

Contribution To Literature:

Atrial fibrillation (AF) was noted to be a risk marker for stroke in the Framingham cohort in 1978. Since then anticoagulation is an important part of managing AF. Use of aspirin in patients with AF is a common practice based on this notion that it might add to prevention of MI or stroke in such patients. The ORBIT-AF study tackled this question by determining the risk factors associated with concomitant use of aspirin and oral anticoagulation (OAC) in patients with AF.

Study Design

The present study was a retrospective review of ORBIT-AF prospective registry that enrolled 7.347 patients with AF on OAC. The ORBIT-AF registry enrolled patients from 174 US sites. Follow up period of this review was of 6 months and the primary outcomes that were studied were: bleeding, hospitalization, CV events, and mortality.

Inclusion Criteria

  • Age ≥ 18 years
  • Atrial fibrillation on EKG

Exclusion Criteria

  • Anticipated life expectancy <6 months
  • Atrial flutter only
  • Patients not taking oral anticoagulant
  • Patients taking antiplatelet therapies other than ASA
  • Transient AF secondary to a reversible condition
  • Current enrollment in a randomized clinical trial of antithrombotic therapy for AF

AF Characterisitcs:

Among 7347 patients, 4804 were on OAC alone and 2543 patients were on both OAC plus aspirin.

Overall (n=7347) OAC Alone (n=4804) OAC+ASA (n=2543)
AF type, %
 New onset 4.0 3.8 4.6
 Paroxysmal 46 45 47
 Persistent 18 18 18
 Long-standing persistent 32 33 30

Primary Outcomes

  • After adjustment for baseline characteristics the primary outcomes for OAC vs OAC + ASA were as follows:
    Risk of major bleeding: HR 1.53 (1.20–1.96), p = 0.0006
    (note, the risk for bleed is almost 1.5 times for OAC + ASA compared to OAC alone)
    All-Cause Hospitalization: HR 1.08 (1.00–1.17), p = 0.06
    Mortality: HR 1.26 (0.98–1.63), p = 0.08


The present study indicates worse outcomes in terms of major bleeding and also indicates towards higher mortality and hospitalizations but the latter results are not significant.  Based on the real-world National Cardiovascular Data Registry (NCDR) Practice Innovation and Clinical Excellence (PINNACLE) registry more than one-third of 210,380 patients who had CHA2DS2-VASc scores ≥2 were treated with aspirin alone, and not with oral anticoagulants as per ACC/AHA/HRS guidelines. (2) Using OAC is important for prevention of stroke in patients with AF and this has been presented in a number of studies. However, the use of aspirin in addition to OAC in AF has always been questioned. The current study tackled this very question. The results suggest that we should avoid combination therapy in patients who do not have history of CAD. While in patients with history of CAD, using combination therapy outweighs the risks. Note The 2011 ACC/AHA/HRS guidelines recommend using ASA + OAC in patients with history of MI. However, 2014 guidelines have not commented on combination therapy.


  1. Wolf PA, et al. “Epidemiologic assessment of chronic atrial fibrillation and risk of stroke: The Framingham study.” Neurology.1978;28(10):973-977.
  2. Hsu J.C., Maddox T.M., Kennedy K., et al. (2016) Aspirin instead of oral anticoagulant prescription in atrial fibrillation patients at risk for stroke. J Am Coll Cardiol 67:2913–2923.