Cochrane for Clinicians

Putting Evidence into Practice

Effectiveness and Safety of Factor Xa Inhibitors in Patients with Atrial Fibrillation


Am Fam Physician. 2019 Oct 1;100(7):405-406.

Author disclosure: No relevant financial affiliations.

Clinical Question

Are factor Xa inhibitors as effective and safe as vitamin K antagonists in the prevention of embolic events in patients with atrial fibrillation (AFib)?

Evidence-Based Answer

Treatment of AFib with a factor Xa inhibitor results in a decrease in the combined end point of stroke and embolic events (odds ratio [OR] = 0.89; 95% CI, 0.82 to 0.97), as well as a decrease in intracranial hemorrhage (OR = 0.50; 95% CI, 0.42 to 0.59) and all-cause mortality (OR = 0.89; 95% CI, 0.83 to 0.95) compared with warfarin (Coumadin) therapy.1 (Strength of Recommendation: A, based on consistent, good-quality patient-oriented evidence.)

Practice Pointers

AFib affects 2.7 to 6.1 million Americans. Patients with AFib have a four- to fivefold increased risk of embolic stroke vs. those without.24 In addition to rate control, a mainstay of AFib treatment focuses on anticoagulation to prevent thrombus formation and decrease stroke risk. Before the introduction of factor Xa inhibitors, the vitamin K antagonist warfarin was the anticoagulant used most often. Use of warfarin, however, requires laborator y monitoring and dietar y restrictions that are challenging for patients and clinicians. The authors of this review examined the effectiveness and safety of factor Xa inhibitors compared with warfarin in preventing stroke and embolic events in patients with AFib.

This review included 13 randomized controlled trials with 67,688 participants with mean and median ages ranging from 65 to 74 years.1 These trials directly compared factor Xa inhibitors with dose-adjusted warfarin. Seven factor Xa inhibitors were represented in the trials, but studies looking at apixaban (Eliquis), edoxaban (Savaysa), and rivaroxaban (Xarelto) contributed 90% of the data. Factor Xa inhibitors significantly decreased the incidence of the primary outcome, all strokes and systemic embolic events, compared with warfarin (OR = 0.89; 95% CI, 0.82 to 0.97; 13 studies; n = 67,477). Age-related subgroup analysis revealed that all

Author disclosure: No relevant financial affiliations.


show all references

1. Bruins Slot KM, Berge E. Factor Xa inhibitors versus vitamin K antagonists for preventing cerebral or systemic embolism in patients with atrial fibrillation. Cochrane Database Syst Rev. 2018;(3):CD008980....

2. Centers for Disease Control and Prevention. Division for heart disease and stroke prevention. Atrial fibrillation fact sheet. Updated August 22, 2017. Accessed July 2, 2018.

3. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke. 1991;22(8):983–988.

4. Henriksson KM, Farahmand B, Åsberg S, et al. Comparison of cardiovascular risk factors and survival in patients with ischemic or hemorrhagic stroke. Int J Stroke. 2012;7(4):276–281.

5. January CT, Wann LS, Alpert JS, et al. 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 Practice Guidelines and the Heart Rhythm Society [published correction appears in J Am Coll Cardiol. 2014;64(21):2305–2307]. J Am Coll Cardiol. 2014;64(21):e1–e76.

6. Kirchhof P, Benussi S, Kotecha D, et al.; ESC Scientific Document Group. 2016 ESC guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. 2016;37(38):2893–2962.

7. Drug price information. Accessed July 2, 2018.

These are summaries of reviews from the Cochrane Library.

This series is coordinated by Corey D. Fogleman, MD, assistant medical editor.

A collection of Cochrane for Clinicians published in AFP is available at



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