By Tim Drake, PharmD, MBA, BCPS

Assistant Professor of Pharmacy, College of Pharmacy, Roseman University of Health Sciences, South Jordan, UT

Dr. Drake reports no financial relationships relevant to this field of study.

SYNOPSIS: More patients with atrial fibrillation may receive anticoagulation, according to new recommendations.

SOURCE: Lip GYH, et al. Antithrombotic therapy for atrial fibrillation: Chest guideline and expert panel report. Chest 2018; Aug 21. pii: S0012-3692(18)32244-X. doi: 10.1016/j.chest.2018.07.040. [Epub ahead of print].

The decision to use antithrombotic (aspirin, clopidogrel) or anticoagulation (warfarin, apixaban, rivaroxaban) therapy to prevent stroke in patients with atrial fibrillation must account for the patients’ risk for stroke compared to their risk for bleeding. The CHADS2 and, more recently, the CHA2DS2VASc scores are used to quantify the stroke risk in patients with atrial fibrillation and provide clarification on the risk-benefit ratio of bleeding vs. stroke prevention.2 Under previous direction, the recommendation was to consider no therapy for those with a CHA2DS2VASc score of 0, to offer antithrombotic therapy (aspirin) or anticoagulation therapy to patients at low stroke risk (CHA2DS2VASc = 1), and to offer anticoagulation to those patients at higher risk (CHA2DS2VASc ≥ 2). Patients with a score of 2 had an annual adjusted stroke rate of 2.2%.3

The American College of Chest Physicians recently published new evidence-based guidelines on the use of antithrombotic therapy.1 A list of key updates is presented below:

  • While the CHA2DS2VASc score remains in use, the new guidelines do not consider gender in determining risk for the basis of treatment;
  • Larger emphasis placed on determining low-risk patients using CHA2DS2VASc;
  • For a non-sex risk score of 0, no antithrombotic or anticoagulation therapy is indicated;
  • For a non-sex risk score of ≥ 1, consider anticoagulation therapy;
  • For nonvalvular atrial fibrillation in patients without chronic kidney disease, novel oral anticoagulants (NOACs; apixaban, dabigatran, rivaroxaban) are preferred over warfarin to prevent stroke;
  • Special attention should be given to reduce modifiable bleeding risk factors;
  • Dual or triple therapy with anticoagulation and antiplatelet agents should be limited, used only for a limited time after percutaneous coronary intervention and based on the patient’s risk of bleeding;
  • Patients with nonvalvular atrial fibrillation taking warfarin with a CHA2DS2VASc score of ≤ 1 do not require bridging prior surgery.

The CHA2DS2VASc score has been shown to accurately determine which patients are at low risk for stroke. Additionally, since the female sex criterion is only relevant as a risk factor for patients > age 65 years or with an additional risk factor, it makes sense to not use this score to determine if a patient is at low risk. Therefore, the term non-sex risk factor is used. For patients with no non-sex risk factors, the risk of stroke is very low and there is a strong recommendation not to offer therapy to reduce stroke risk.1 NOACs (dabigatran, rivaroxaban, apixaban, and edoxaban) are preferred over vitamin K antagonists (VKAs; warfarin) in patients with nonvalvular atrial fibrillation. In trials comparing NOACs vs. warfarin, NOACs have shown to be at least as safe and effective as warfarin. NOACs provide predictable anticoagulant effects, are shorter-acting, onset rapidly, and carry fewer drug/dietary restrictions compared to warfarin.1 Data on aspirin and other antithrombotic medications have been inconsistent in showing benefit for stroke prevention. The authors of the AVERROES trial found a significant benefit with apixaban compared to aspirin with similar rates of major bleeding.4 Thus, with the strong recommendation to use NOACs over VKAs, the safety and efficacy of the NOAC apixaban over aspirin, and the conflicting evidence of aspirin, it is reasonable to drop antiplatelet/antithrombotics from consideration to prevent stroke in patients with atrial fibrillation.1 At every visit, providers should address bleeding risk, paying particular attention to modifiable risk factors. The HAS-BLED Score is a tool that can be used to determine bleeding risk factors, but should not be used to recommend against anticoagulation therapy. The major modifiable risk factors are blood pressure control, appropriate anticoagulation therapy/control, decreased use of nonsteroidal anti-inflammatory drugs and antiplatelet agents, moderation of alcohol intake, limited use of bridging, ending participation in high-risk activities that can cause trauma, and treatment of anemia or a low platelet count.1


The new guidelines include anticoagulation for stroke prophylaxis for patients with a CHA2DS2VASc score ≥ 1. A score of 1 corresponds to an adjusted stroke rate of 1.3% per year.3 In the ARISTOTLE trial, the rate of major bleeds with apixaban was 2.13% per year.5 Although many major bleeds can be managed and may not be as debilitating as a stroke, the risk-benefit ratio is not as clear at this level. Additionally, if warfarin is used, the risk of a major bleed increases to 3.09% per year.5 The risk-benefit ratio is clearer when looking at only the rate of intracranial hemorrhage (0.33% per year with apixaban).5 Finally, these factors re-enforce the importance of reducing the modifiable bleeding risk factors in patients on anticoagulation. The approximate percentage of patients with atrial fibrillation who score 1 on the CHA2DS2VASc scale is 9.5%.2 With an estimated 2.7-6.1 million people in the United States with atrial fibrillation, these new recommendations could increase the number of people receiving anticoagulation by 250,000-580,000.3 Considering that the average cost of NOACs is $500 per month, the potential increase in yearly drug cost to the U.S. healthcare system could be $1.5-3.5 billion. The decreased risk of stroke with the accompanying morbidity and mortality would need to be considered to provide a full cost-benefit analysis.


  1. Lip GYH, et al. Antithrombotic therapy for atrial fibrillation: Chest guideline and expert panel report. Chest 2018; Aug 21. pii: S0012-3692(18)32244-X. doi: 10.1016/j.chest.2018.07.040. [Epub ahead of print].
  2. Lip GY, et al. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: The euro heart survey on atrial fibrillation. Chest 2010;137:263-272.
  3. January CT, 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. J Am Coll Cardiol 2014;64:e1-76.
  4. Connolly SJ, et al. Apixaban in patients with atrial fibrillation. N Engl J Med 2011;364:806-817.
  5. Granger CB, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011;365:981-992.