Patients with atrial fibrillation have a higher risk for stroke than the general population, and that risk increases markedly with age.

Anticoagulation therapy lowers the risk of stroke and improves all-cause mortality. Warfarin has been the mainstay of anticoagulation therapy for decades but has an increased risk of major bleeding and requires a complicated administration regimen.

A recent update of research adds to the evidence about the relative benefits and harms of newer anticoagulation therapies and tools to predict stroke related to atrial fibrillation and bleeding risk. This evidence on the newer therapies, along with recently updated guidelines on managing nonvalvular atrial fibrillation, can help inform clinician and patient decisions on anticoagulant use and may potentially reduce the risk of stroke and its consequences.

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A 2018 systematic review update supported by the Patient-Centered Outcomes Research Institute (PCORI) through a research partnership with the Agency for Healthcare Research and Quality (AHRQ)1,2 found new evidence suggesting that direct oral anticoagulants (DOACs) are as or more effective than warfarin in preventing strokes related to atrial fibrillation, with similar or lower risks of major bleeding. The update also found that clinical tools such as the CHADS2, CHA2DS2-VASc, and HAS-BLED can assist clinicians in predicting risk of stroke and bleeding and help guide management of atrial fibrillation.

Comparison of DOACs with Warfarin

Anticoagulant Risk of stroke or embolism Risk of major bleeding
Apixaban (Eliquis®) Lower than warfarin Lower than warfarin
Dabigatrani (Pradaxa®) Lower than warfarin Same as warfarin
Edoxaban (Savaysa®, Lixiana®) Same as warfarin Lower than warfarin
Rivaroxaban (Xarelto®) Same as warfarin Similar or possibly higher than warfarin*

i150 mg dose

*NOTE: Inconsistencies between randomized controlled trial and observational data indicate the risk of major bleeding may be higher among those taking rivaroxaban than those taking warfarin.

Source: Sanders et al., 2018.

Risk Assessment

  • The CHADS2 and CHA2DS2-VASc tools demonstrated comparable prediction ability.
  • The HAS-BLED risk score tool was better able to predict major bleeding events than other tools.

What Do Current Guidelines Say?

The American College of Cardiology (ACC), American Heart Association (AHA), the Heart Rhythm Society (HRS),3 and the American Academy of Family Physicians (AAFP)4 publish guidelines on assessing risks of stroke and bleeding and on anticoagulant use for patients with atrial fibrillation.

Table 1. Summary of Practice Guidelines

Source Assessing stroke risk Assessing bleeding risk Anticoagulant use
(updated 2019)
Use CHA2DS2-VASc score
HAS-BLED score can be used to determine bleeding risk in patients considering anticoagulants
For women with a CHA2DS2-VASc score of 2 or greater and men with a score of 3 or greater, treat nonvalvular atrial fibrillation or atrial flutter with a DOAC rather than warfarin
(updated 2017)
No preference for the CHA2DS2-VASc score over the CHADS2 score
HAS-BLED score can be used to determine bleeding risk and is slightly better for identifying the risk in patients taking warfarin
Chronic anticoagulation is recommended for patients who have atrial fibrillation unless they are at low risk of stroke (CHADS22<2 or have specific contraindications. Choice of anticoagulation therapy should be based on patient preferences and patient history

Talking with Patients about Anticoagulants


A consumer-friendly version of this update is available here to help support clinicians’ conversations with patients and caregivers about anticoagulant use and the trade-offs in choosing a medication. Topics for discussion include:

The benefits and risks of anticoagulant use
The patient’s risk assessment tool scores and what they mean when balancing the risk of stroke from atrial fibrillation with the risk of bleeding associated with anticoagulant use
The fact that anticoagulants do not treat atrial fibrillation so patients should not expect the anticoagulants to improve their atrial fibrillation
The importance of talking to a clinician before patients stop taking the medication
Weighing other factors that may influence a patient’s decision to use a DOAC or warfarin, such as

  • Age and other factors that may affect risk of stroke or bleeding related to atrial fibrillation
  • The need for regular lab testing while taking warfarin to monitor the blood’s ability to clot
  • The lack of widespread availability and guidelines for use of DOAC reversal agents
  • Insurance coverage and out-of-pocket costs
  • The importance of taking medication at the same time every day and monitoring for food, alcohol, and drug interactions
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About the Evidence

This Evidence Update is based on a recently updated systematic review1 which included 320 articles presenting findings from 185 studies published between January 2000 and February 2018. The report updates an earlier version published in 2013.

View the full systematic review update at

Download this Evidence Update


1. © 2011–2020 Patient-Centered Outcomes Research Institute. “Stroke Prevention in Atrial Fibrillation Patients: A Systematic Review Update.” Last updated February 20, 2020.

2. Sanders GD, Lowenstern A, Borre E, et al. Stroke Prevention in Patients With Atrial Fibrillation: A Systematic Review Update. This systematic review was supported by PCORI through a research partnership with AHRQ. Rockville, MD: AHRQ Publication No. 18-EHC018-EF; 2018. Washington, DC: PCORI Publication No. 2018-SR-04; 2018. DOI:

3. January CT, Wann LS, Calkins H, et al. 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/ American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2019. pii: S0735-1097 (19)30209-8. doi: 10.1016/jjacc.2019.01.011.

4. Frost JL, Campos-Outcalt D, Hoelting D, LeFevre M, Lin KW, Vaughan W, Bird MD. Updated Clinical Practice Guideline: Pharmacological Management of Newly Detected Atrial Fibrillation. Published April 2017. Available at the American Academy of Family Physicians website: Accessed February 27, 2020.

The information in this publication is not intended to be a substitute for professional medical advice.

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