Author: Stormi Gale, PharmD, BCPS
One of the major changes in the 2014 American College of Cardiology/American Heart Association/Heart Rhythm Society (ACC/AHA/HRS) guidelines for the management of patients with atrial fibrillation (AF) was the introduction of the CHA2DS2-VASc score for evaluating thromboembolic risk.1 An advantage of the additional risk factors in the CHA2DS2-VASc score (female sex, ages 65 to 75 years, and history of vascular disease) is the ability to better recognize patients who are truly low versus intermediate risk of stroke.2 Unfortunately, although the guidelines clearly advocate for anticoagulation in patients with a CHA2DS2-VASc score of 2 or greater, the recommendations for patients at low (CHA2DS2-VASc 0) and in particular intermediate (CHA2DS2-VASc 1) risk of stroke are less clear (Table 1).
Table 1. Antithrombotic Recommendations for Atrial Fibrillation in Recent Guidelines
|0||No antithrombotic therapy or aspirin||It is reasonable to omit therapy||No antithrombotic therapy|
|1||OAC (preferred) or DAPT||OAC or no antithrombotic therapy or aspirin||Consider OAC
Abbreviations: ACC, American College of Cardiology; ACCP, American College of Chest Physicians; AHA, American Heart Association; DAPT, dual-antiplatelet therapy; ESC, European Society of Cardiology, HRS, Heart Rhythm Society; OAC, oral anticoagulation
Historically, guidelines recommended aspirin in all patients with a CHADS2 score of zero.5 However, more recent versions suggest that withholding antithrombotic therapy is a viable option for this low-risk population. As previously mentioned, the updated risk-stratification system allows for improved identification of patients who are truly low risk. For example, the annual stroke risk in a patient with a CHADS2 score of 0 has been reported to be as high as 3.2% per year.2 However, utilizing the CHA2DS2-VASc score, patients with low risk scores have rates of less than 1% (Table 2).6,7 This includes female patients with no other risk factors, as data suggest that female sex alone does not increase the risk for stroke.8,9
A study utilizing data from Danish registries evaluated the net clinical benefit of no antithrombotic therapy, aspirin, or warfarin in AF patients with 0-1 stroke risk factors.10 In patients at low risk of stroke (CHA2DS2-VASc 0 for males, 1 for females), antithrombotic therapy with either aspirin or warfarin was associated with either a neutral effect or net clinical harm. As such, the most recent AF guidelines from the European Society of Cardiology (ESC) do not recommend antithrombotic therapy in this population.4
There is ambiguity across the guidelines regarding AF stroke prevention in intermediate-risk patients (Table 1). The ESC guidelines recommend weighing the expected benefits and risks as well as patient preference to determine the appropriate therapy.4 One of the reasons for this uncertainty is that not all risk factors in the CHA2DS2-VASc score carry the same stroke risk. A study of 186,570 patients with AF who were not on any antithrombotic therapy demonstrated a 2.75% annual stroke risk for men with a CHA2DS2-VASc score of 1; however, male patients who received one point for vascular disease had a 1.95% per year stroke risk compared to 3.5% per year for those aged 65 to 74 years.11 Similarly, for females with a CHA2DS2-VASc score of 2, the risk of stroke appeared lower for patients with hypertension (1.91% per year) but was again highest in those aged 65 to 74 years (3.34%). Therefore, it may be advisable to evaluate patients at intermediate-risk for stroke based on individual risk factors rather than the score itself (i.e., greater consideration in a 67-year-old male than a 54-year-old female with controlled hypertension). Furthermore, when evaluating stroke risk it is also important to consider patient preference as part of the plan. Studies have shown that patients are more concerned about preventing strokes than increasing their risk of bleeding and are reportedly willing to endure 4.4 major bleeds to prevent one stroke.12
|Score||Adjusted stroke rate
(% per year)
|Score||Adjusted stroke rate
(% per year)
Aspirin vs. Oral Anticoagulation
The most common reason that patients are treated with aspirin in place of oral anticoagulation (OAC) is out of concern for bleeding. While many healthcare professionals perceive the risk of bleeding with OAC to be much greater than that of antiplatelet therapy, available data do not support this notion. The Birmingham Atrial Fibrillation Treatment of the Aged (BAFTA) study randomized 973 patients over the age of 75 with AF to either warfarin (target INR 2-3) or aspirin 75 mg daily for a mean of 2.7 years.17 Investigators found a significant reduction in the primary endpoint of fatal or disabling stroke, intracranial hemorrhage, or clinically significant arterial embolism with warfarin therapy (1·8% vs 3·8%, RR 0.48, 95% CI 0·28–0·80, p=0·003). However, no difference in hemorrhagic stroke or any major hemorrhage (p=0.83 and 0.90, respectively) was observed.
Furthermore, aspirin was again compared to OAC in the AVERROES (Apixaban Versus Acetylsalicylic Acid to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment) study, which included 5599 patients at least 50 years of age with AF (36.5% with a CHADS2 of 0-1).18 The primary endpoint of stroke or systemic embolism was reduced with apixaban vs. aspirin (1.6% vs. 3.7%, HR 0.45, 95% CI, 0.32 to 0.62; P<0.001). A subgroup analysis demonstrated no difference in efficacy between aspirin and apixaban in patients with lower risk scores (CHADS2 0-1); however, because the study utilized CHADS2 and combined the subgroup of patients with a score of 0-1, the number of patients with a truly low risk of stroke is unclear. Similar to what was observed in BAFTA, there was no difference in major or clinically relevant non-major bleeding outcomes between OAC and aspirin therapy. This evidence suggests that OAC does not confer a greater risk of bleeding compared to aspirin in older patients and should therefore be the preferred therapy for stroke prevention in AF.
In summary, although practice often entails anticoagulating patients with a CHA2DS2-VASc of 2 or greater and not in those with lower scores, more consideration should be given to each patient’s individual stroke risk. The development of the CHA2DS2-VASc risk scoring system allows clinicians to identify patients at truly low risk (CHA2DS2-VASc 0 for males, 1 for females) who generally do not require antithrombotic therapy for stroke prevention. Patients with an intermediate CHA2DS2-VASc score (particularly CHA2DS2-VASc 1 for males) should still be considered as possible candidates for OAC, as individual risk factors (e.g., age) confer greater degrees of stroke risk. Patient preferences regarding perceived value of stroke prevention versus bleeding risk should also be discussed and considered when making decisions regarding therapy. Aspirin should not be utilized as a means of mitigating bleeding risk in patients in whom stroke prevention is indicated as studies have shown similar bleeding risk to OAC therapy despite decreased efficacy.
Stormi Gale, PharmD, BCPS
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- 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. J Thromb Haemost. 2012;10(9):1745-1751.
- 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 Int J Med. 2014;107(12):955-967.
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- Chao T-F, Liu C-J, Wang K-L, et al. Should atrial fibrillation patients with 1 additional risk factor of the CHA2DS2-VASc score (beyond sex) receive oral anticoagulation? J Am Coll Cardiol. 2015;65(7):635-642.
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