Stroke Prophylaxis in Non-Valvular Atrial Fibrillation
Atrial fibrillation (AF) is the most common cardiac arrhythmia; lifetime risk for the devel-
opment of AF is 1 in 4 in people 40 years of age and older. 1 AF is also a powerful and inde-
pendent risk factor for stroke. The availability of oral anticoagulation agents, such as warfarin
or other vitamin K antagonists, provides a substantial opportunity to reduce the relative risk
of stroke or other cardioembolic events by >60%. In comparison, antiplatelet agents such as
acetylsalicylic acid (ASA) reduce the risk by only 20%-33%. 2 Unfortunately, several compli-
cations are also associated with warfarin use, such as the risk of increased bleeding and drug
interactions. Despite risks and inconveniences, the evidence weighs strongly in favour of anti-
coagulation with warfarin for most patients, with a few notable exceptions. In light of the
importance of optimal management for stroke prophylaxis and recent data regarding the effi-
cacy of warfarin in certain high-risk populations, this issue of Cardiology Rounds reviews the
strategies for simplifying the management of patients with AF.
Estimating the risk for stroke in patients with nonvalvular AF
The first step, which influences all other aspects of stroke prophylaxis in AF, is to assess the
risk of stroke for each individual. This process allows both physician and patient to assess the
potential benefit of anticoagulation therapy. Several scoring systems have been developed for
predicting the risk of stroke in the setting of nonvalvular AF. These include the Stroke Prevention
in Atrial Fibrillation (SPAF), Atrial Fibrillation Investigators (AFI), and CHADS 2 scoring
systems, and they all appear to have similar predictive value; 3 however, these scoring systems
apply specifically to nonvalvular AF. Patients with valvular lesions such as mitral stenosis, rheu-
matic heart disease, a history of valve repair or valve replacement are generally at higher risk for
embolic events and are outside of the scope of this article.
Among these scoring systems for nonvalvular AF, the CHADS 2 scoring system has received
the most widespread adoption and has been well validated. The CHADS 2 score is easy to
remember (Table 1) and easy to calculate. Explicitly including the CHADS 2 score as part of each
office visit or consultation for patients with AF provides a quick method to reassess whether anti-
coagulation is indicated. The score may need to be updated over time, as patients develop new
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risk factors, such as advanced age. Importantly, the CHADS 2 score provides a framework for
discussions with the patient concerning the risks and benefits of stroke prophylaxis.
Once calculated, the score can be used to provide reasonable guidance to the annual risk for
stroke per year. While each point on the CHADS 2 score adds to the risk for an embolic event,
there is some disparity between the published results on absolute event rates in the absence of
anticoagulation. In the most frequently cited study on event rates (National Registry
of Atrial Fibrillation, published in 2001), 4 over 1,700 patients with a diagnosis of AF were
followed for >1 year; one-third of these patients were taking ASA and the rest received neither
ASA nor warfarin. Events in this registry included transient ischemic attacks, strokes, and the
International Classification of Diseases, Clinical Modification (ICD-9-CM) codes for new
diagnoses of cerebrovascular disease.
A later meta-analysis 5 by the same research group revealed slightly lower event rates in a group of patients who used ASA alone as stroke prophylaxis. The Birmingham Atrial Fibrillation Treatment of the Aged (BAFTA) trial 6 had a control arm of elderly patients in whom physicians were uncertain as to the benefits and risks of oral anticoagulation over ASA; therefore, they excluded many patients at high
risk of either stroke or bleeding. The event rates in the BAFTA trial for patients on ASA alone were lower than anticipated for CHADS 2 scores 4 ≥3 (5% vs an anticipated 9%).
This lower than anticipated event rate may reflect improved control of blood pressure and lipids in the past decade, but may also reflect a selection bias for the study. Over 45% of patients screened for the BAFTA trial were excluded on the basis of either patient or physician preference for warfarin.
Thus, the event rates in the BAFTA trial, as shown in Table 2, may underestimate the risks of embolization in patients not taking warfarin. Despite the disparities between these reports, the event rates of all patients with a CHADS 2 score of ≥1 are sufficiently high to warrant strong consideration for
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anticoagulation with warfarin. While the CHADS 2 score includes factors considered high risk for stroke, other factors considered more “moderate” include female sex, age 65-74 years, and the
presence of established coronary artery disease (Table 3). As will be discussed later, one of these more moderate risk factors may make it reasonable to consider the use of ASA or warfarin in patients who otherwise have a CHADS 2 score of 0.
A few additional rules of thumb may further help to simplify risk stratification.
Rule #1 – There is clear evidence that patients with persistent AF, paroxysmal AF, and atrial flutter all have a very similar risk for cardioembolic events. Therefore, a level 1 recommendation from the American Heart Association (AHA) 7 is that the selection of a stroke prophylaxis regimen, if any, should be guided by the same process for all 3 of these conditions.
• Rule #2 – Once a patient is found to have AF, it should be assumed that they have it for the rest of their lives, unless it occurred in the setting of a clearly reversible cause that has been treated successfully (such as a pulmonary embolism, alcohol binge, postoperative AF after cardiac surgery, or hyperthyroidism). In other words, once warfarin is started, it is usually “started for life” in the absence of contraindications. Even in the setting of a clearly reversible cause of AF, the selected regimen for prophylaxis against embolism should continue for a sufficient period to allow any potential thrombi that have formed to clear (at least 4 weeks after resolution of the reversible cause). The possibility that the AF may have existed independent of a presumed reversible cause must also be considered before assuming that the patient’s AF has resolved completely. Given the high prevalence of AF, many patients with reversible
causes will still have recurrences of AF once the presumed reversible cause has resolved.
• Rule #3 – Any patient with AF should be considered for stroke prophylaxis therapy regardless of whether he/she is rate-controlled or converted back into sinus rhythm (by either pharmacologic means or electrical [DC] cardioversion).
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