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As a result, chronic antithrombotic therapy with either oral anticoagulation (ie, a vitamin K antagonist,
direct thrombin inhibitor, or factor Xa inhibitor) or antiplatelet therapy is considered for most of these
patients. Both therapies are effective in preventing clinical systemic embolization, although
anticoagulant therapy is far more effective and preferred in all but the lowest-risk patients. As
antithrombotic therapy is associated with an increased risk of bleeding, its use must take both benefit
and risk into account.
Many [1-10], but not all [11], of the major clinical trials of antithrombotic therapy and subsequent meta-
analyses have excluded patients with any type of prosthetic heart valves, those with mitral stenosis, and
those with decompensated valvular heart disease who were likely to require valve replacement in the
near future. Based on these studies, the newer anticoagulants should not be prescribed for these
patients. Anticoagulation in these patients is discussed separately.
Although the risk models discussed above are generally similar in terms of their moderate predictive
ability, we believe that the CHADS2 score (table 1) is the easiest to implement and most clinically useful
model for risk stratification of patients with nonvalvular AF (calculator 1).
The American College of Cardiology Foundation/American Heart Association/European Society of
Cardiology (ACC/AHA/ESC) guidelines for the management of patients with AF have not recommended
use of a particular risk stratification scheme [13,54,55]. The 2010 European Society of Cardiology
guidelines for the management of AF recommended use of the CHADS2 score [56]. For those patients
with CHADS2 scores of 0 or 1, the additional use of CHA2DS2-VASc (table 3) was recommended
CHADS2 score, thromboembolic risk, and effect of warfarin anticoagulation
Clinical parameter Points
Congestive heart failure (any history) 1
Hypertension (prior history) 1
Age ≥75 years 1
Diabetes mellitus 1
Secondary prevention in patients with a prior ischemic stroke or a transient ischemic attack; most
experts also include patients with a systemic embolic event 2
CHADS2 score Events per 100 person-years* NNT
Warfarin No warfarin
0 0.25 0.49 417
1 0.72 1.52 125
2 1.27 2.50 81
3 2.20 5.27 33
4 2.35 6.02 27
5 or 6 4.60 6.88 44

NNT: number needed to treat to prevent one stroke per year with warfarin.
* The CHADS2 score estimates the risk of stroke, which is defined as focal neurologic signs or symptoms
that persist for more than 24 hours and that cannot be explained by hemorrhage, trauma, or other
factors, or peripheral embolization, which is much less common. Transient ischemic attacks are not
included. All differences between warfarin and no warfarin groups are statistically significant except for
a trend with a CHADS2 score of 0. Patients are considered to be at low risk with a score of 0, at
intermediate risk with a score of 1 or 2, and at high risk with a score ≥3. One exception is that most
experts would consider patients with a prior ischemic stroke, transient ischemic attack, or systemic
embolic event to be at high risk even if they had no other risk factors and therefore a score of 2.
However, the great majority of these patients have some other risk factor and a score of at least 3.

Data from: Go AS, Hylek EM, Chang Y, et al. JAMA 2003; 290:2685; and CHADS2 score from Gage BF,
Waterman AD, Shannon W. JAMA 2001; 285:2864.
Prevention approach by CHADS2 score — Long-term antithrombotic therapy, usually with anticoagulant
therapy, is recommended for most patients with AF who have CHADS-2 risk factors for stroke. While all
current risk stratification schemes, which include the individual risk factors, provide only modest
capacity to predict stroke risk, the CHADS2 score (table 1) is simple and well validated. As a result, our
recommendations for antithrombotic therapy depend on the CHADS2 scheme [13,14]. (See "Risk of
embolization in atrial fibrillation".)

We suggest the following approach to antithrombotic therapy, which is based on evidence provided by
the many studies of antithrombotic therapy discussed below (see 'Studies of anticoagulant
monotherapy' below and 'Alternatives to anticoagulant monotherapy' below):

●Patients with a CHADS2 score of 0 who receive no antithrombotic therapy are at low risk of stroke
(rate of 0.5 to 1.7 percent per year), and a benefit from aspirin has not been conclusively shown in these
patients. Thus, we suggest no antithrombotic therapy, as the risks likely outweigh the benefits.

Patients with a CHADS2 score of 1 are at intermediate risk of stroke (2.0 percent per year, or perhaps
somewhat less) and should be treated with oral anticoagulant therapy or aspirin (75 to 325 mg daily).
Based on the studies discussed below, which show that anticoagulant is more effective than aspirin, we
prefer anticoagulant therapy to aspirin in most CHADS2 patients with a score of 1, especially for patients
more fearful of stroke as compared with bleeding.

The choice between anticoagulation and aspirin will depend upon many factors, including the clinician's
assessment of risk, the ability to provide high-quality monitoring of the intensity of oral anticoagulation
(if warfarin is chosen as the anticoagulant) and regimen compliance, the patient's risk of bleeding with
oral anticoagulation, and patient preference (including issues related to cost, convenience of
monitoring, and dose frequency). Patient preference is an important issue, since the absolute reduction
in stroke risk is likely to be small, but stroke remains a feared outcome. Better patient education can
improve understanding of the benefits and risks of anticoagulant therapy [21].

The role of dual antiplatelet therapy with aspirin plus clopidogrel remains unclear in patients with a
CHADS2 score of 1 who do not wish to take anticoagulant therapy, for reasons such as the
inconvenience of INR monitoring or cost of the newer agents. Dual antiplatelet therapy and oral
anticoagulation have similar bleeding risks, as shown in the ACTIVE W trial. Such an approach may be
reasonable for patients who require dual antiplatelet therapy for other reasons, such as those with
coronary stent placement or acute coronary syndrome. (See 'Aspirin plus clopidogrel' below.)

As antiplatelet therapy is inferior to anticoagulant therapy with regard to efficacy, patients should be
fully informed of this fact before a decision is made to choose antiplatelet therapy. If the reason for not
choosing anticoagulant therapy is concern about bleeding, aspirin plus clopidogrel is not beneficial, as
the combination produces a similar risk of bleeding to that seen with warfarin.

●Patients with a CHADS2 score of 2 or higher are at relatively high risk of stroke (at least 4 percent per
year). Thus, oral anticoagulant therapy is strongly recommended for most patients with a CHADS2 score
of 2 or higher [22].

●The RE-LY, ROCKET-AF, and ARISTOTLE trials (table 2), compared warfarin with dabigatran,
rivaroxaban, and apixaban, respectively, came to similar conclusions regarding the efficacy and safety of
these newer antithrombotic agents compared to warfarin in non-valvular AF. We prefer dabigatran,
rivaroxaban, or apixaban to warfarin in most cases in which oral anticoagulant therapy is chosen.

The following are situations in which it is reasonable to prefer warfarin instead of these newer

•Patients already on warfarin who are comfortable with periodic INR measurement and whose INR has
been relatively easy to control.

•Patients who are not likely to comply with the twice daily dosing of dabigatran or apixaban.

•Patients for whom the use of any of these other anticoagulants will lead to an unacceptable increase in

•Patients with chronic severe kidney disease, whose estimated creatinine clearance is less than 30
mL/min. (See "Management of thromboembolic risk in patients with atrial fibrillation and chronic kidney
disease", section on 'Benefits and risks of oral antithrombotic therapy'.)

Prevention approach by CHA2DS2-VASc score — Some of our authors and reviewers, who support the
use of the CHA2DS2-VASc score (table 3), consider it reasonable to choose antithrombotic therapy for
patients with none of the CHADS2 but one of the additional CHA2DS2-VASc risk factors: age 65 to 74
years, female sex, and evidence of atherosclerotic cardiovascular disease. Benefit from therapy in such
patients has not been established in randomized trials.

These authors and reviewers agree with the 2012 focused update of the European Society of Cardiology
guidelines for the management of AF, which makes the following recommendations [23]:

●The CHA2DS2-VASc score is strongly preferred to the CHADS2 score.

●For patients with a CHA2DS2-VASc score of ≥2, a strong recommendation for oral anticoagulant
therapy is made.

●For patients with a CHA2DS2-VASc score of 1 (but a CHADS2 score of 0), a weak recommendation for
oral anticoagulant therapy is made. Aspirin is not recommended. (See 'Risk stratification to guide
therapy' above and "Risk of embolization in atrial fibrillation".)

●In patients with a CHA2DS2-VASc score of 0, no antithrombotic therapy is recommended.

Dabigatran, rivaroxaban, and apixaban have not been studied in this lower risk population.