Classification of Atrial Fibrillation per ACC/AHA/ESC*

1) Paroxysmal Atrial Fibrillation: atrial fibrillation episodes last < 7 days, usually < 24 hours 2) Persistent Atrial Fibrillation: lasts > 7 days, may be paroxysmal if it recurs after reversion, recurrent when a patient experiences 2 or more episodes 3) Permanent Atrial Fibrillation: lasts more then one year and cardioversion has not been attempted or fails 4) Lone Atrial Fibrillation: describes paroxysmal, persistent, or permanent atrial fibrillation in individuals without structural heart disease

The incidence of thromboembolism depends in part on the type of atrial fibrillation. The majority of clinical trials have been conducted in patients with persistent or permanent atrial fibrillation. However, embolic events have been shown to occur in patients with atrial fibrillation for as little as 72 hours (3). Therefore, patients with paroxysmal atrial fibrillation should be anticoagulated if present for a substantial portion of time.

*ACC=American College of Cardiology, AHA=American Heart Association, ESC=European Society of Cardiology

Epidemiology:

Atrial fibrillation is the most common clinically significant arrhythmia seen in primary care. It affects 0.4% of the population in general, increasing with age to affect 6-10% of the population over age 75 (4). Atrial fibrillation increases the risk of stroke 6 fold when compared to patients with normal sinus rhythm and 20-30% of acute ischemic strokes are cardioembolic in origin (5). The risk of stroke in patients with untreated atrial fibrillation is approximately 6% per year (1).

Pathophysiology of Stroke in Atrial Fibrillation:

Blood stasis in the left atrium and left atrial appendage along with activation of the hemostatic system leads to intra-atrial clot formation. The clot can then pass through the left ventricle, aorta, carotid arteries and subsequently obstruct the cerebral vasculature.

Prevention Modalities:

Multiple studies have been done to evaluate both aspirin and warfarin therapy in primary prevention of stroke. Conflicting results have been obtained with regard to aspirin. However, a meta-analysis of 6 trials comparing aspirin to placebo found that aspirin decreased the incidence of stroke 22% (6). It also appears that aspirin is more helpful when used in low risk patients which will be defined later.

Adjusted dose warfarin, on the other hand, has been shown to consistently work well for stroke prevention and to be superior to aspirin in this regard. Warfarin decreases the risk of stroke by 62-68% with an absolute annual reduction of 2.7-3.1% (7). Therefore, treating 100 patients with warfarin will decrease 3 strokes per year. When compared to aspirin, warfarin decreases the risk of stroke by 2-3 times, but increases the risk of major bleeding 1.5 times (8).

Combined low dose warfarin and aspirin have been studied for use in primary stroke prevention and have been shown to cause a higher morbidity and mortality when compared to adjusted dose warfarin and should therefore not be used in this setting (9).

Risk Stratification:

The choice of treatment modality in stroke prevention must take into account the benefits of stroke prevention versus the risk of bleeding. Therefore, several studies have been done to determine risk stratification in regards to treatment choice. Based on the information obtained a number of risk models have been developed. These include:

The Stroke Prevention in Atrial Fibrillation (SPAF) investigators

The sixth American College of Chest Physicians (ACCP) Consensus Conference

Guidelines from the ACC/AHA/ESC

The pooled analysis from the five randomized, primary stroke prevention trials in patients with atrial fibrillation: BAATAF, SPINAF, AFASAK, CAFA, SPAF (10-14). All the models agreed on the following high risk features:

prior embolic event

LV dysfunction or heart failure

valvular heart disease

hypertension

older age The ACCP and ACC/AHA/ESC also included as risk factors:

DM

CAD

thyrotoxicosis

The different models varied on the age at which risk was increased independent of other risk factors:

women >75 years in SPAF

75years as high risk, and 65-75 years as moderate risk in the ACCP Consensus

75 years in the ACC/AHA/ESC guidelines The ACC/AHA/ESC guidelines are shown below.

Additional guidelines from the ACC/AHA/ESC include:

1) For primary prevention of embolism in patients over age 75 years, target a lower INR of 2 (range 1.6-2.5) 2) INR should be determined at least weekly during the initiation of oral anticoagulation therapy and monthly when the patient is stable. 3) Anticoagulate patients with atrial fibrillation lasting more than 48 hours or of unknown duration for at least 3-4 weeks before and after cardioversion (INR 2-3).

Clinical Evaluation and Assessment of Patients with Atrial Fibrillation:

Obtain a complete history and physical and update this in the chart at each visit. This should include any additional risk factors for stroke that would place the patient in a high risk category as listed above. Also include additional modifiable stroke risks such as smoking, high fat diet, alcohol use, etc. Assess the type of atrial fibrillation, duration and any pharmacologic agents the patient is taking. Also, be sure to assess the patient’s risks for potential bleed if started on anticoagulants such as history of GI bleed or intracranial bleed, is the patient at risk for frequent falls, etc.

An EKG should be present on the chart to confirm the rhythm and evaluate for any other abnormalities: previous MI, other arrhythmias, LVH. The patient should also have a CXR done at some point to assess cardiac silhouette, vasculature, lung parenchyma. A cardiac echo should be done to evaluate for valvular disease, ejection fraction, and evidence of thrombus. Laboratory studies should be done to assess TSH, lipid profile, and electrolytes and repeated as indicated.

Additional tests to consider if indicated include exercise testing, holter monitor, transesophageal echocardiogram and electrophysiological studies.

If the patient is started on adjusted dose warfarin therapy there needs to be clear documentation of management with appropriate follow up as listed previously.

Summary:

Atrial fibrillation is the most common arrhythmia seen by primary care physicians. It increases with age and is associated with an increased risk of stroke due to thromboembolism. Oral anticoagulants have been shown to decrease the risk of stroke in patients with atrial fibrillation. While there is conflicting literature in regards to the efficacy of aspirin in this setting it does seem to decrease the risk of stroke in low risk patients and is associated with less risk of bleeding then warfarin. Warfarin on the other hand has been consistently shown to decrease the risk of stroke in patients with atrial fibrillation. The risk of bleeding versus the reduction in stroke incidence must be weighed out in each patient individually. There have been multiple studies to help risk stratify those at highest risk of thromboembolism and stoke. These high risk patients are appropriate candidates for warfarin therapy. However, lifestyle, drug interactions, compliance, risk of falls, and other associated risks should be discussed prior to the initiation of adjusted dose warfarin therapy. Finally, close follow up of patients on warfarin to insure appropriate INR level should be emphasized.

Additional Reading and Resources:

American College of Cardiology American Heart Association

American Stroke Association American Academy of Family Physicians: Stroke Monograph 256, 2000 (not available online)

Bibliography:

1. Rosenfeld JA. AAFP Monograph 256: Stroke. 2000. 2. Gorelilicck PB, Saaco RL, Smith DB, et al. Prevention of a first stroke: a review of guidelines and a multidisciplinary consensus statement from the National Stroke Association. JAMA. 1999;281:1112-1120. 3. Hart RG, Pearce LA, Rothbart RM, et al. Stroke with intermittent atrial fibrillation: incidence and predictors during aspirin therapy. Stroke Prevention in Atrial Fibrillation Investigators. J Am Coll Cardiol 2000;35:183. 4. Fuster V, Ryden LE, Asinger RW, et al. ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation: Executive Summary. J Am Coll Cardiol. 2001;38:1231. 5. Evans A, Kalra K. Are the Results of Randomized Controlled Trials on Anticoagulation in Patients with Atrial Fibrillation Generalizable to Clinical Practice? Arch Intern Med. 2001;161(11):1443-1447. 6. Hart, RG, Benavente O, McBride R, et al. Antithrombotic therapy to prevent stroke in patients with atrial fibrillation: A meta-analysis. Ann Intern Med 1999;131:492. 7. Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation. Analysis of pooled data from five randomized controlled trials. Arch Intern Med 1994;154:1449. 8. Manning WJ, Hakan A, Furie EL, et al. Anticoagulation to prevent embolization in atrial fibrillation. Up To Date, April 2003 9. Adjusted-dose warfarin versus low-intensity, fixed-dose warfarin plus aspirin for high-risk patients with atrial fibrillation: Stroke Prevention in Atrial Fibrillation III randomized clinical trial. Lancet 1996;348:633. 10. The Boston Area Anticoagulation Trial for Atrial Fibrillation Investigators. The effect of low dose warfarin on the risk of stroke in patients with nonrheumatic atrial fibrillation. N Engl J Med 1990;323:1505. 11. SPINAF; Ezekowitz MD, Bridgers SL, Janes KE, et al. Warfarin in the prevention of stroke associated with nonrheumatic atrial fibrillation. N Engl J Med 1992;327:1406 12. Petersen P Boysen G, Godfredsen J, et al. Placebo-controlled, randomized trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation the Copenhagen AFASAK Study. Lancet 1989;1:175 13. Connolly SJ, Laupacis A, Gent M et al. Canadian Atrial Fibrillation Anticoagulation (CAFA) Study. J Am Coll Cardiol. 1991;18:349 14. Stroke Prevention in Atrial Fibrillation Investigators. Stroke prevention in atrial fibrillation study: Final results. Circulation 1991;84:527