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Author: Stormi Gale, PharmD, BCCP

The highly anticipated focused update of the 2014 American Heart Association/American College of Cardiology/Heart Rhythm Society (AHA/ACC/HRS) atrial fibrillation (AF) guideline incorporates new recommendations based on the evidence from several recent publications.1,2 There are several modified recommendations that may change the management of patients in your practice. Here are four of the most notable updates:

1) Indications for anticoagulation have changed
No need to learn a new risk-score as the CHA2DS2-VASc score remains the preferred risk stratification system, as has the recommendation for anticoagulation in males with a score of 2 or greater. However, there is a modified recommendation for females, who now only require anticoagulation for a CHA2DS2-VASc score of 3 (previously 2) or greater. This is due to an abundance of data that suggests female sex in the absence of other risk factors does not increase the risk of stroke.3,4 Yet, there is still a role for this component of the risk score as female sex does increase the incidence of stroke in the presence of other risk factors. Thus, female sex should still play a role when making clinical decisions (e.g., risk/benefit of stroke/bleed, need for bridging). The update still suggests it is reasonable to omit anticoagulation in those without any non-sex risk factors (CHA2DS2-VASc score of 0 in men or 1 in women), and clinical judgment remains the major factor in deciding whether to anticoagulate patients with only one non-sex risk factor (CHA2DS2-VASc score of 1 in men and 2 in women). However, aspirin is no longer mentioned as an option for patients considered to be low-risk, as the benefits of this have not been shown to outweigh the risk of bleeding.5 For a more comprehensive explanation of these data and how to manage patients with lower CHA2DS2-VASc scores, check out one of our previous blogs here.

2) The definition of valvular atrial fibrillation is re-explained
Although direct oral anticoagulants (DOACs) are preferred to warfarin for prevention of thromboembolism in nonvalvular AF, warfarin remains the anticoagulant of choice in patients with valvular AF based on previous data that demonstrated worse outcomes with DOACs in this population.6 While it might seem obvious to some, the term valvular heart disease in the setting of AF stroke prevention does not include patients with any type of valvular heart disease. In fact, the definition of valvular heart disease includes only those with a mechanical heart valve or moderate-to-severe mitral stenosis. To decrease the confusion surrounding this terminology, the guidelines begin by emphasizing this definition and avoiding the term nonvalvular by specifying those without either of the aforementioned criteria. In the case of other valvular disorders, a meta-analysis of these data has actually demonstrated improved outcomes with DOACs over warfarin in these patients.7 The update only vaguely addresses bioprosthetic valves, suggesting that more evidence is needed before these DOACs can be routinely recommended for long-term use. However, the evidence is a bit more favorable regarding their role in this population compared to 2014, as preliminary subanalyses of these patients who were included in landmark DOAC studies do not appear to demonstrate worse outcomes.8,9

3) Apixaban is now a supported option in patients with end stage renal disease
Although I suspect that many of us have been doing this in our practice for some time, apixaban is finally recommended as a reasonable alternative to warfarin in patients with concomitant AF and end-stage renal disease (ESRD). This is a result of apixaban’s favorable pharmacokinetic profile as well as a few small observational studies (explained in a previous blog) that suggest apixaban may be safe and effective in these patients. Although rivaroxaban has also undergone similar studies in ESRD, a higher-risk of bleeding-related adverse outcomes has been demonstrated in registry data, and its use is not condoned by the update.10–12 As such, apixaban is the only anticoagulant other than warfarin that is currently recommended in patients with concomitant AF and ESRD.

4) Managing antithrombotic therapy in concomitant AF and ACS is updated
Balancing the risks of thromboembolism and bleeding in the setting of recent cardiac stenting and AF has been a highly debated topic over the years. The use of triple therapy lost some favor with the publication of the WOEST trial, although the need to weigh risks and benefits has remained prudent.13 The focused update recommends that for those deemed to require triple therapy, a limited duration of 4 to 6 weeks may be considered. This is supported by published evidence that demonstrated no benefit with longer durations of triple therapy compared to an abbreviated duration14,15. However, because this is a weak recommendation, the decision to use triple therapy at all should be based on clinical judgment of perceived risk/benefit. Additionally, the role of DOACs in this population was further specified, with recommendations for dabigatran or dose-reduced rivaroxaban (i.e., 15 mg daily) in combination with clopidogrel to minimize bleeding. Studies of these regimens did not detect a difference in cardiovascular death, myocardial infarction, or stroke compared to standard triple therapy; however, it is important to note that they were not powered to evaluate the risk of stent thrombosis or systemic embolism.16,17 This is particularly important with regards to rivaroxaban, as the recommended dose for this indication is lower than what is recommended for atrial fibrillation alone. It is unclear if full dose rivaroxaban plus clopidogrel would be associated with similar thromboembolic or bleeding outcomes.


Other, less altering changes include the addition of edoxaban to the list of DOAC options in AF, as this drug was approved after the release of the 2014 guidelines. In addition, the update reiterates that the decision to anticoagulate should not be contingent on paroxysmal versus permanent AF. Betrixaban did not make the update due to lack of Food and Drug Administration approval for this indication at the time of publication.

Bottom Line
Although the focused update of the 2014 AHA/ACC/HRS AF guideline incorporate modified recommendations based on evidence from several recent publications, the overall management of these patients is similar to current practice. Perhaps the most important change for clinicians to incorporate into practice is to only consider anticoagulation in females if their CHA2DS2-VASc score is 3 or greater, rather than 2 from the previous guideline. The update also gives clinicians more confidence in the use of apixaban in ESRD, clarifies the definition of nonvalvular AF, and provides more guidance in managing patients with concomitant indications for anticoagulation and dual antiplatelet therapy for AF and acute coronary syndromes, respectively.


Stormi Gale, PharmD, BCCP

Dr. Gale is an assistant professor in the Department of Pharmacy Practice and Science at the University of Maryland School of Pharmacy, and practices as a clinical pharmacy specialist at the University of Maryland Medical Center in Baltimore, MD. Follow her on Twitter @stormigale.


  1. 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. Journal of the American College of Cardiology. January 2019:25873.
  2. 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. Circulation. January 2014:CIR.0000000000000041.
  3. Mikkelsen AP, Lindhardsen J, Lip GYH, Gislason GH, Torp-Pedersen C, Olesen JB. Female sex as a risk factor for stroke in atrial fibrillation: a nationwide cohort study. Journal of Thrombosis and Haemostasis. 2012;10(9):1745-1751.
  4. Wagstaff AJ, Overvad TF, Lip GYH, Lane DA. Is female sex a risk factor for stroke and thromboembolism in patients with atrial fibrillation? A systematic review and meta-analysis. QJM. 2014;107(12):955-967.
  5. Mant J, Hobbs FR, Fletcher K, et al. Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial. The Lancet. 2007;370(9586):493-503.
  6. Eikelboom JW, Connolly SJ, Brueckmann M, et al. Dabigatran versus Warfarin in Patients with Mechanical Heart Valves. New England Journal of Medicine. 2013;369(13):1206-1214.
  7. Pan K-L, Singer DE, Ovbiagele B, Wu Y-L, Ahmed MA, Lee M. Effects of Non-Vitamin K Antagonist Oral Anticoagulants Versus Warfarin in Patients With Atrial Fibrillation and Valvular Heart Disease: A Systematic Review and Meta-Analysis. J Am Heart Assoc. 2017;6(7).
  8. Pokorney Sean D, Rao Meena P, Wojdyla Daniel M, et al. Abstract 17277: Apixaban Use in Patients With Atrial Fibrillation With Bioprosthetic Valves: Insights From ARISTOTLE. Circulation. 2015;132(suppl_3):A17277-A17277.
  9. Carnicelli Anthony P., De Caterina Raffaele, Halperin Jonathan L., et al. Edoxaban for the Prevention of Thromboembolism in Patients With Atrial Fibrillation and Bioprosthetic Valves. Circulation. 2017;135(13):1273-1275.
  10. Dias C, Moore KT, Murphy J, et al. Pharmacokinetics, Pharmacodynamics, and Safety of Single-Dose Rivaroxaban in Chronic Hemodialysis. AJN. 2016;43(4):229-236.
  11. De Vriese AS, Caluwé R, Bailleul E, et al. Dose-finding study of rivaroxaban in hemodialysis patients. Am J Kidney Dis. 2015;66(1):91-98.
  12. Chan KE, Edelman ER, Wenger JB, Thadhani RI, Maddux FW. Dabigatran and Rivaroxaban Use in Atrial Fibrillation Patients on Hemodialysis. Circulation. 2015;131(11):972-979.
  13. Dewilde WJ, Oirbans T, Verheugt FW, et al. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial. The Lancet. 2013;381(9872):1107-1115.
  14. Fiedler KA, Maeng M, Mehilli J, et al. Duration of Triple Therapy in Patients Requiring Oral Anticoagulation After Drug-Eluting Stent Implantation: The ISAR-TRIPLE Trial. J Am Coll Cardiol. 2015;65(16):1619-1629.
  15. Koskinas KC, Räber L, Zanchin T, et al. Duration of Triple Antithrombotic Therapy and Outcomes Among Patients Undergoing Percutaneous Coronary Intervention. JACC: Cardiovascular Interventions. 2016;9(14):1473-1483.
  16. Cannon CP, Bhatt DL, Oldgren J, et al. Dual Antithrombotic Therapy with Dabigatran after PCI in Atrial Fibrillation. New England Journal of Medicine. 2017;377(16):1513-1524.
  17. Gibson CM, Mehran R, Bode C, et al. Prevention of Bleeding in Patients with Atrial Fibrillation Undergoing PCI. New England Journal of Medicine. 2016;375(25):2423-2434.
4 Updates Every Clinician Should Know About the 2019 AF Guidelines

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